CA1281640C - Antigen bound by two monoclonal antidodies - Google Patents
Antigen bound by two monoclonal antidodiesInfo
- Publication number
- CA1281640C CA1281640C CA000382964A CA382964A CA1281640C CA 1281640 C CA1281640 C CA 1281640C CA 000382964 A CA000382964 A CA 000382964A CA 382964 A CA382964 A CA 382964A CA 1281640 C CA1281640 C CA 1281640C
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- Prior art keywords
- antibody
- process according
- antigen
- labelled
- sample
- Prior art date
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- Expired - Lifetime
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/576—Immunoassay; Biospecific binding assay; Materials therefor for hepatitis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/577—Immunoassay; Biospecific binding assay; Materials therefor involving monoclonal antibodies binding reaction mechanisms characterised by the use of monoclonal antibodies; monoclonal antibodies per se are classified with their corresponding antigens
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2470/00—Immunochemical assays or immunoassays characterised by the reaction format or reaction type
- G01N2470/04—Sandwich assay format
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/971—Capture of complex after antigen-antibody reaction
Abstract
Abstract of the Disclosure More rapid and sensitive "two-site" or "sandwich"
immunometric assay techniques are disclosed for determination of the presence and/or concentration of antigenic substances in fluids using monoclonal antibodies as compared to conven-tional assays using polyclonal antibodies. Also described are inhibition assays using complexes of antigens with a monoclonal antibody.
immunometric assay techniques are disclosed for determination of the presence and/or concentration of antigenic substances in fluids using monoclonal antibodies as compared to conven-tional assays using polyclonal antibodies. Also described are inhibition assays using complexes of antigens with a monoclonal antibody.
Description
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IMMUNOMETRIC AND INHIBITION ASSAYS
USING MONOCLONAL ANTIBODIES
This invention relates to methods for detecting and/or determining the concentration of antigenic sub-stances in fluids such as serum. In another aspect it relates to immunometric and inhibition assay techniques.
In yet another aspect it relates to monoclonal anti-bodies.
The determination of the presence or concentration of antigenic substances, for example, those associated with a wide variety of physiological disorders, in serum 10 or other body fluids relies increasingly upon immunoassay techniques. These techniques are based upon formation of a complex between the antigenic substance being assayed and an antibody or antibodies in which one or the other member of the complex may be labelled, for example, by a radioactive element such as 125I, which permits its detection and/or quantitative analysis after separation of the complexed labelled antigen or antibody from uncomplexed labelled antigen or antibody.
In the case of a competition immunoassay technique, 20 the antigenic substance in a sample of fluid being tested for its presence competes with a known quantity of labelled antigen for a limited quantity of antibody binding sites. Thus, the amount of labelled antigen bound to the antibody is inversely proportional to the amount of antigen in the sample. By contrast, immuno-metric assays employ a labelled antibody. In such an assay, the amount of labelled antibody associated with ~,~," --1--~28~640 the complex is proportional to the amount of antigenic substance in the fluid sample.
Immunometric assays have been found to be particu-larly well suited for the detection of polyvalent anti-gens, i.e., antigenic substances that are able to complex with two or more antibodies at the same time. Such assays typically employ a quantity of unlabelled antibody bound to a solid support that is insoluble in the fluid being tested and a quantity of soluble antibody bearing a lO label such as a radioactive isotope that permits detec-tion and/or a quantitative estimate of the amount of the ternary complex formed between solid phase antibody, antigen, and labelled antibody.
In immunometric assays known to the prior art, typically "forward" a~sayæ, in which the antibody bound to the solid phase is first contacted with the sample being tested to extract the antigen from the sample by formation of a binary solid phase antibody: antigen complex, are employed. After a suitable incubation 20 period, the solid support is washed to remove the residue of the fluid sample, including unreacted antigen, if any, and then contacted with a solution containing a known quantity of labelled antibody.
After a second incubation period to permit the labelled antibody to complex with the antigen bound to the solid support through the unlabelled antibody, the solid support is washed a second time to remove the unreacted labelled antibody. In a simple "yes/no" assay to determine whether the antigen is present in the sample 30 being tested, the washed solid support is tested to ~Z8~6~D
detect the presence of labelled antibody, for example, by measuring emitted radiation if the label is a radioactive element. The amount of labelled antibody detected is compared to that for a negative control sample known to be free of the antigen. Detection of labelled antibody in amounts substantially above the background levels indicated by the negative control is interpreted to indicate the presence of the suspect antigen. Quanti-tative determinations can be made by comparing the 10 measure of labelled antibody with that obtained for calibrated samples containing known quantities of the antigen.
This kind of assay is frequently referred to as a "two-site" or "sandwich" assay since the antigen has two antibodies bonded to its surface at different loca-tions. This and related techniques are described by Wide at pp. 199-206 of "Radioimmunoassay Methods, n Edited by Kirkham and Hunter, E. & S. Livingstone, Edinburgh, 1970. An assay based on this technique for the detection 20 of the antigen associated with serum hepatitis using an 5I labelled antibody is described in U.S. Patent 3,867,517.
Despite their great utility, the prior art immuno-,:
~ metric assays have been recognized to be slow procedures, :: :
in part because two washing steps are required andbecause lengthy incubation periods are required to approach equilibrium, i.e., the point at which the amount ~;~ of complex formed does not change with increasing time.
To eliminate at least one of the washing steps 30 associated with this procedure, so-called "simultaneous"
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~ -3-6~0 and "reverse" assays have been proposed. A simultaneous assay involves a single incubation step as the antibody bound to the solid support and the labelled antibody are both added to the sample being tested at the same time.
After the incubation is completed, the solid support is washed to remove the residue of fluid sample and uncom-plexed labelled antibody. The presence of labelled antibody associated with the solid support is then determined as it would be in a conventional "forward"
10 sandwich assay.
A reverse assay involves the stepwise addition first of a solution of labelled antibody to the fluid sample followed by the addition of unlabelled antibody bound to a solid support after a suitable incubation period. After a second incubation, the solid phase is washed in conventional fashion to free it of the residue of the sample being tested and the solution of unreacted labelled antibody. The determination of labelled anti-body associated with the solid support is then determined 20 as in the simultaneous and forward assays.
Both the simultaneous and reverse assay techniques require a sufficient excess amount of solid phase anti-body to bind most or all of the antigen present to avoid a high dose hook effect where artifically negative or low quantitation of antigen is observed at extremely high concentrations of antigen. For this reason, the forward assay has been the approach preferred by the prior art.
That is because ward assay has been the approach prefer-red by the prior art. That is because large amounts of 30 highly purified, active antibody specific to the antigen ~8~640 of interest for preparing a solid phase with sufficient antigen binding capacity is difficult to obtain from the "polyclonal" antibodies used in prior art processes.
When an immunogenic substance is introduced into a living body, the body's immune system reacts by generating antibodies to every site on the immunogen it recognizes.
A large immunogenic protein molecule may have dozens of sites and a foreign cell may have hundreds. Thus, while each antibody producing cell produces antibody specific 10 for a single antigenic site the immune system has genera-ted a specie of specific antibody producing cells for each immunogenic site recognized. In addition, the body has produced relatively large quantities of antibodies to antigens other than the one of interest such that most of the antibody in the polyclonal mixture is not specific for the antigen of interest. Accordingly, the antibodies used in prior immunometric assays are necessarily "poly-clonal n in nature since the antibodies are derived from antisera raised in a conventional manner in animals and 20 their purification is difficult. Methods for affinity purifying such antibodies have generally been time consuming and resulted in low yields and loss of high affinity antibodies.
When employing conventional polyclonal antibody mixtures in the reverse and simultaneous assays, the formation of a "sandwich" comprising the antigen com-plexed by two or more labelled antibodies which complex with the antigen at dlfferent sites is possible. These complexes could remain soluble in the sample being 30 tested, be removed by subsequent washing steps, and not : : :
1~816~0 "counted" when the solid phase is analyzed for solid phase bound labelled antibody. If this happens to a significant extent, sensitivity of the assay is reduced and erroneous results may arise. However, if the unla-belled bound antibody is added to the sample first as in the forward sandwich assay, steric considerations prevent formation of a sandwich comprising the antigen complexed to two or more unlabelled antibodies where labelled antibody is excluded from also binding to the 10 antigen. Accordingly, the antigen is free to react with a labelled antibody molecule. Nevertheless, it has been proposed to use a simultaneous assay for human thyroid stimulating hormone (HTSH) by employing a large excess of the unlabelled antibody bound to a solid phase to mini-mize formation of a soluble complex by soluble labelled antibodies. See Jeong et al., "Comparison of Radioim-munoassay (RIA) with a Unique, Single-Incubation Two-Site Immunoradiometric Assay (IRMA) as Applied to the Deter-mination of Human Thyroid Stimulating Hormone (HTSH),"
20 Bio-Rad Laboratories, 1979.
A variation of a simultaneous assay is described in U.S. 4,174,384. In that assay, separate portions of AntiIgG (Human) are labelled, respectively, with a fluorescing chromophore (fluorescein) and a chromophore (rhodamine) which absorbs light emitted by the fluo-rescein. Both antibodies, in a soluble form, are con-tacted with a sample containing human IgG. Reaction of the Anti-IgG with the IgG may bring the two chromophores close enough together, i.e., within 100 angstroms or 30 less, that the emission of light by the fluorescing 6~0 chromophore is absorbed (quenched) by the other. The percentage of maximum fluorescence for the sample is determined and used as a measure of the amount of IgG in the sample.
It has also been proposed to use a reverse assay for HTSH, hepatitis associated antigen (HA~) and car-cinoembryonic antigen (CEA) by employing a quantity of labelled antibody sufficient to assure a labelled anti-body: antigen complex but insufficient to form a "sand-10 wich" of all the antigen present in a sample. See U.S.Patent No. 4,098,876.
Since all three of the procedures known to the prior art use a polyclonal mixture of antibodies, the potential for cross-reaction with other materials in serum or other fluid than the antigen for which the test is intended is increased. The occurrence of cross-re-activity with other antigens also reduces the sensitivity of the test for the suspect antigen and increases the prospect of a "false-positive" assay. Furthermore, the 20 use of polyclonal antibodies in a simultaneous or reverse ~ assay requires a careful consideration of the amount of labelled antibody used relative to the amount of solid phase antibody and/or antigen present. In the case of using fluorescence quenching, sensitivity is reduced because the minimum spacing between the fluorescing chromophore and the quenching chromophore is not assured when polyclonal antibodies are employed.
In view of these shortcomings, the limitations to the immunometric procedures known to the prior art are 30 readily apparent. The conventional forward assays are ; -7-lZ8~0 accomplished with fewer steps but require large quanti-ties of solid phase specific antibody and are not well suited to determination of small concentrations of antigen since formation of a sandwich of the antigen with a multiple number of labelled antibody molecules competes with formation of the sandwich comprising bound antibody:antigen:labelled antibody or, in the case of using fluorescence quenching, the formation of a sand-wich without pairing of a fluorescent chromophore with a quenching chromophore is possible; and all are subject to misinterpretation of false-positives due to the polyclonal nature of the antibody.
Accordingly, the present invention is directed towards the provision of an improved process for the immunometric assay for antigenic substances, which permits more rapid immunometric assay techniques and more sensitive immunometric assay techniques.
With the present invention, the polyclonal anti-bodies used in an immunometric assay, for example, as the unlabelled antibody bound to a solid support and the antibody used as the soluble labelled antibody or, in the case of assays relying upon fluorescence quenching, the antibodies carrying a fluorescing or quenching chromophore are replaced by two or more monoclonal antibodies.
According to one aspect of the invention, there is provided an improvement in an immunometric assay process .
. - .
~ ` - ,:
~2~3~6~0 to determine the presence or concentration of an anti-genic substance in a fluid sample comprising forming a ternary complex of the antigenic substance, a first antibody and a second antibody bound to the antigen at a different site than the first antibody by contacting the sample with said first and second antibodies, the improvement comprising employing a monoclonal antibody for each of said first and second antibodies.
In a preferred embodiment of the invention, the monoclonal antibody used as the antibody bound to a solid support is the product of a different cell line than is the monoclonal antibody used for the labelled antibody and the two monoclonal antibodies are selected to bind the antigenic substance at sitee remote from each other so a~ to not interfere with the other's binding to the antigen. In the case of fluorescence quenching, the two antibodies are also usually the products of different cell lines and are selected so as to not interfere with the other's binding yet bring the two chromophores close enough together to permit quench-ing of fluorescence, i.e., usually to within about 100 angstroms. The advantages of the present invention, particularly in simultaneous and reverse assays, over prior art methods will become clear after consideration of the accompanying drawings and the following detailed description of the invention.
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, 16~0 Also, according to the present invention, monoclon-al antibodies are employed in inhibition assays. In such assays, a known quantity of an antigen and mono-clonal antibody is contacted with a sample suspected of containing an antigen corresponding to the known antigen added within the monoclonal antibody. The extent to which inhibition of the complex between the antibody and antigen occurs because a complex comprising the monoclonal antibody and antigen from the sample is formed is a measure of the presence and/or amount of antigen in the sample assayed.
Further, according to another aspect of the inven-tion, there is provided a process for the determination of the presQnce or concentration of an antig~nic substancQ in a fluid, comprising the stQps of:
(a) contacting a sample of the fluid with a known quantity o~ added antigenic substance and a monoclonal antibody to the antigenic substance, and ~ b) measuring the inhibition of formation of a complex between the antibody and added antigenic sub-stance by combination of said monoclonal antibody and the antigenic substance in the fluid to form a second complex.
In a preferred embodiment, the antibody and antigen are bound, respectively, to one of the members of a pair of fluorescing and quenching chromophores. Inhibition of the formation of a complex between the labelled ~:
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, -- . . ~ ' . . ~; -: - .. . .: - . ; .
- ... . . . . :
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--antigen and antibody by antigens in the sample being assayed leads to a reduction in quenching and an increase in fluorescence. The extent of the inhibition of quenching is a measure of antigen concentration in the sample. In another preferred embodiment of an inhibition assay, the known antigen and antibody the original compLex are bound to particles, for example, latex particles, of a size which permits agglomerates to form. When a sample suspected of containing antigen is contacted with the antibody and bound antigen, inhibi-tion of agglomerate formation occurs because of complex-ing between the bound antibody and sample antigen which cannot form agglomerates. The reduction in agglomera-tion can be measured using turbidimetric techniques.
According to a further aspect of the invention, there i~ provided a process for the determination of the presence or concentration of an antigenic substance in a fluid, comprising the steps:
(a) contacting a sample of the fluid with a soluble first monoclonal antibody to the antigenic substance in order to form a soluble complex of the antibody and antigenic substance present in the sample, the first monoclonal antibody being labelled;
(b) contacting the soluble complex with a second monoclonal antibody bound at the time of the determin-ation to a solid carrier, the solid carrier being insoluble in the fluid, in order to form an in~oluble ., - .
: . . . . .
: :' .. - - : . , : . , .
l2a~640 lla complex of the first monoclonal antibody, the antigenic substance and the second monoclonal antibody bound to the 801 id carrier;
(c) separating the solid carrier from the fluid sample and unreacted labelled antibody;
(d) measuring either the amount of labelled anti-body associated with the solid carrier or the amount of unreacted labelled antibody; and (e) relating the amount of labelled antibody measured with the amount of labelled antibody measured for a control sample prepared in accordance with steps (a)-(d), the control sample being Xnown to be free of the antigenic substance, to determine the presence of antigenic substancQ in the fluid sample, or relating : 15 the amount of labelled antibody measured with the amount o~ labelled antibody mQasured for samples containing known amounts of antigenic substance prepared in accor-dance with steps (a)-(d) to determine the concentration : of antigenic substance in the fluid sample.
-: 20 According to an additional aspect of the invention, there is provided a process for the determination of the presence of an antigenic substance in a fluid comprising the steps:
a) simultaneously contacting a sample of the .::
~: 25 fluid with first and second monoclonal antibodies to the antigenic substance, the first monoclonal antibody ,~ being labelled and the second monoclonal antibody being 'i~
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llb bound at the time of the determination to a solid carrier insoluble in the fluid, in order to form an insoluble complex of the first monoclonal antibody, the antigenic substance and the second monoclonal antibody;
b) separating the solid carrier from the fluid sample and unreacted labelled antibody;
c) measuring either the amount of labelled antibody associated with the solid carrier or the amount of unreacted labelled antibody; and d) relating the amount of labelled antibody measured with the amount of labelled antibody measured for a control sample prepared in accordance with steps (a)-(c), the control sample being known to be free of the antigenic substance, to determine the presence of antigenic substance in the fluid sample, or relating the amount of labelled antibody measured with the amount of labelled antibody measured for samples containing known amounts of antigenic substance prepared in accor-dance with steps (a)-(d) to determine the concentration of antigenic substance in the fluid sample.
In a yet further aspect of the present invention, there is provided an improvement in an immunometric assay for the determination of the presence or concen-tration of an antigenic substance in a sample of a fluid comprising forming a ternary complex to a first labelled antibody, the antigenic substance, and a second antibody, the second antibody being bound at the ! I ~
~ ~r ~z~
llc time of the determination to a carrier insoluble in the fluid, the improvement comprising employing a mono-clonal antibody for each of the labelled antibody and the antibody bound to a solid carrier.
The present invention also includes a kit for effecting an immunometric assay and, accordingly, yet another aspect of the invention provides an improvement in an immunometric assay kit for the determination of the presence or concentration of an antigenic substance lo in a sample of a fluid comprising reagents for forming a ternary complex to a first labelled antibody, the anti-genic substance, and a second antibody, the second antibody being bound at the time of the determination to a carrier in~oluble in the ~luid, the improvement comprising employing a monoclonal antibody for each of the labelled antibody and the antibody bound to a solid carrier.
Further, the present invention provides a reagent for immunological assay of antigens based on the sand-, - 20 wich method, characterized in that it comprises insolubilized monoclonal antibody and labelled mono-clonal antibody, the monoclonal antibodies respectively being capable of distinguishing and binding to different ~ antigen determinants of an antigen to be assayed.
`~ 25 Additionally, the present invention provides an improved sandwich method for immunolo~ical assay of - antigens wherein the improvement resides in the fact -: . . .
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lld that insolubilized antibody and labelled antibody react simultaneously with an antigen to be assayed, the insolubilizQd antibody and labelled antibody comprising monoclonal antibodies capable of distinguishing and respectively binding to different antigen determinants of the antigen.
Yet further, the present invention provides an improved sandwich method for immunological assay of antigens wherein the improvement resides in the fact that insolubilised antibody and labelled antibody react simultaneously or in several incubation steps with an antigen to be assayed, the insolubilized antibody and labelled antibody comprising monoclonal antibodies capable of distingui~hlng and re~pectively binding to di~ferent antigen determinants of the antigen.
Yet another aspect of the present invention pro-vides a mixture of monoclonal antibodies useful in an enhanced sensitivity assay for detecting an antigen in a sample which comprises an effective assaying amount of each of at least two monoclonal antibodies which bind to different antigenic sites on the antigen and which are capable under appropriate conditions of forming a stable complex which includes the antigen and all of the -~ monoclonal antibodies.
In each of the various aspects of the invention as recited above, it is preferred that each of the mono-~; clonal antibodies ha~ an affinity for the antigen of at ,:~
"~ ~
:
, - . . .
:- ~ .. -., . ,, ~ .
~281640 lle least about lo8 liters/mole and, more preferably an affinity of at least about lO9 liters/mole.
In the Examples which appear below, reference is made to the accompanying drawings, wherein:
Fig. 1 is a graph illustrating the results obtained using polyclonal antibodies in four types of immuno-metric assay for human IgE: and Fig. 2 is a similar graph illustrating the differ-ence in results obtained using monoclonal antibodies in the same four types of immunometric assay for human IgE.
As indicated above, according to the present invention, the polyclonal antibody used in an immuno-metric assay for an antigenic substance is replaced by a monoclonal antibody. Similarly, monoclonal antibodies are used in inhibition assays. The present invention is -- -- -: - ~ . . ,-, - ~: , .- - ~
.
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useful for the determination of the presence and concen-tration of a wide variety of antigenic substances in-cluding polyvalent antigenic substances. Accordingly, as used herein, the term antigen or antigenic substance refers broadly to substances to which antibodies can be produced. Among such substances may be mentioned hap-tens, hormones such as insulin and human thyroid stim-ulating hormone (HTSH), gamma globulins, allergens, viruses, virus subunits, bacteria, toxins such as those 10 associated with tetanus and with animal venoms, and even some drugs. Among the specific antigens which may be assayed by the processes of the present invention may be mentioned carcinoembryonic antigen (CEA), hepatitis A and B, hepatitis Non A - Non B, IgE and alphafetoprotein.
The monoclonal antibodies useful in the present invention are obtained by the process discussed by Milstein and Kohler and reported in Nature 256 495-497, 1975. The details of this process are well known and will not be repeated here. However, basically it in-20 volves injecting a mouse, or other suitable animal, withan immunogen. The mouse is subsequently sacrificed and cells taken from its spleen are fused with myeloma cells. The result is a hybrid cell, referred to as a "hybridoma, n that reproduces in vitro. The population of hybridomas is screened and manipulated so as to isolate individual clones each of which secretes a single anti-body species to the antigen. Each individual antibody species obtained in this way is the product of a single cell from the immune animal generated in response to a ~ .
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specific antigenic site recognized on the immunogenic substance.
When an immunogenic substance is introduced into a living host, the host's immune system responds by producing antibodies to all the recognizable sites on the substance. This "shotgun" approach to producing anti-bodies to combat the invader results in the production of antibodies of differing affinities and specificities for the immunogenic substance. Accordingly, after the 10 different hybridoma cell lines are screened to identify those that produce antibody to the desired antigen, the antibodies produced by the individual hybridoma cell lines are preferably screened to identify those having the highest affinity for the immunogenic substance stimulating their original production before selection for use in the present invention. Selection based on this criterion is believed to help provide the increased sensitivity in the immunometric and inhibition assays of the present invention using monoclonal antibody compared 20 to the polyclonal antibody used in the prior art which, at best, has an affinity for the antigen which is roughly the average of the affinities of all antibodies produced by the immune system. Preferably, the monoclonal anti-body selected will have an affinity compatible with the desired sensitivity and range for the test system under consideration. Preferably the antibody will have an affinity oP at least 108 liters/mole and, more prefer-ably, an affinity of at least about lO9 liters/mole.
Furthermore, those monoclonal antibodies having 30 the highest affinities can be further screened by running :::
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a simulated assay on specimens known to give false positive-results with processes employing conventional polyclonal antibodies to identify those monoclonal antibodies which do not cross-react and give false positive results.
8ecause the two-site immunometric assay relies upon formation of an antibody:antigen:antibody sandwich, -usually two different monoclonal antibodies which do not interfere with the binding of each other to the antigen 10 are selected to be the bound antibody and the soluble labelled antibody or the antibody pair when fluorescence ~uenching is used. Since both are necessary to complete the sandwich, reverse and simultaneous assays can be conducted without concern, for example, that a complex of labelled antibody:antigen:labelled antibody will form which will preclude formation of a complex between the antigen and the antibody bound to the solid phase and therein lies a particular advantage of the present invention. Furthermore, a forward assay can be accom-20 plished without the intermediate washing step since thetwo antibodies bind to two different sites. We refer to such a process as a "fast forward" assay.
However, particularly in the case of a forward assay, the same monoclonal antibody can be used for both ~ the labelled antibody and the antibody b~und to the solid ;~ support when the antigenic substance possesses identical antibody binding sites sufficiently remote from each ~; other to allow more than one antibody molecule to be bound at the same time. In such a system, the addition 30 first of the bound antibody to the sample precludes ~8164~
formation of a sandwich because of steric considera-tions. When the labelled monoclonal antibody is sub-sequently added, it is also able to complex with the antigen bound to unlabelled antibody on the solid phase.
The unlabelled monoclonal antibody used in the process of the present invention to extract the antigenic substance from the sample being tested may be immobilized on any of the common supports used in immunometric assays. Among these may be mentioned filter paper, 10 plastic beads or test tubes made from polyethylene, polystyrene, polypropylene or other suitable material.
Also useful are particulate materials such as agarose, cross-linked dextran, and other polysaccharides.
The techniques for bonding antibodies to such materials are well know to those skilled in the art. For example, antibodies may be bound to polysaccharide polymers using the process described in U.S. Patent No. 3,645,852.
The labelled monoclonal antibody used in the present invention may be provided with the same labels used in 20 prior art immunometric assays. ~mong these may be mentioned fluorogenic labels for detection by fluorimetry as described in U.S. Patent No. 3,940,475 and enzymatic markers as described in U.S. Patent No. 3,654,090. It is presently preferred to label the antibody with a radioiso-tope such as 125I using, for example, the procedure of Hunter and Greenwood, Nature, 144 (1962), page 945 or that of David et al., Biochemistry, Vol. 13, pp.
1014-1021, 1974.
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In a typical assay, the amount of labelled antibody associatPd with the insoluble sandwich complex is deter-mined by examination of the insoluble carrier material by suitable means. However, it is also possible to relate the presence or absence of antigen in the fluid sample being assayed to the amount of labelled antibody which does not react during the assay and remains in soluble form.
The advantages of the present invention in which 10 monoclonal antibodies are used in immunometric assays as compared to polyclonal antibodies are seen by reference to the following example. In this example, four com-parative assays, a simultaneous assay, a reverse assay, a forward assay, and a "fast" forward assay, were run using both monoclonal antibody and polyclonal antibody using a standard serum containing 100 IU/ml of human IgE as the positive sample. Normal horse serum containing no IgE
was used as a negative control.
The polyclonal antibody to IgE used as the labelled 20 antibody in the example was obtained from Pharmacia Diagnostics of Piscataway, New Jersey. The polyclonal antibody bound to the solid support was obtained from Tago, Inc. of Burlingame, California.
Monoclonal antibody to IgE was obtained using the method of Milstein and Kohler discussed above. The two antibodies selected each exhibited an affinity for IgE of greater than 109 liters/mole and did not interfere :
with the other's binding to IgE.
The assays were run using unlabelled antibody bound 30 to agarose by the process of U.S. Patent No. 3,645,852.
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Labelling of antibody was by 125I according to the process of David et al. referred to above. Phosphate buffered saline, pH 7.4, was used to wash all samples.
Example 1) Simultaneous Assay Method -Duplicate samples were run in which 100 ~ of a suspension of antibody immobilized on agarose particles was mixed with 100 ~ of specimen (serum) and 100 ~ of soluble 25I-labelled antibody. This mixture was incubated 10 for the specified times shown in Table I (for polyclonal antibody) and Table II (for monoclonal antibody) set forth below, plus 30 minutes. The extra 30 minutes incubation period was added to equalize this assay method with the other assay methods which required an additional 30 minutes incubation time for a second added reagent.
Following the incubation periods the agarose particles were washed by addition of buffer and centrifuged. After removal of the washing liquid by aspiration, the re-sulting pellet of agarose particles was then counted for 20 bound 125I-labelled antibody. The counts obtained for each of the complexes after the specified incubation time are set forth in Tables I and II.
IMMUNOMETRIC AND INHIBITION ASSAYS
USING MONOCLONAL ANTIBODIES
This invention relates to methods for detecting and/or determining the concentration of antigenic sub-stances in fluids such as serum. In another aspect it relates to immunometric and inhibition assay techniques.
In yet another aspect it relates to monoclonal anti-bodies.
The determination of the presence or concentration of antigenic substances, for example, those associated with a wide variety of physiological disorders, in serum 10 or other body fluids relies increasingly upon immunoassay techniques. These techniques are based upon formation of a complex between the antigenic substance being assayed and an antibody or antibodies in which one or the other member of the complex may be labelled, for example, by a radioactive element such as 125I, which permits its detection and/or quantitative analysis after separation of the complexed labelled antigen or antibody from uncomplexed labelled antigen or antibody.
In the case of a competition immunoassay technique, 20 the antigenic substance in a sample of fluid being tested for its presence competes with a known quantity of labelled antigen for a limited quantity of antibody binding sites. Thus, the amount of labelled antigen bound to the antibody is inversely proportional to the amount of antigen in the sample. By contrast, immuno-metric assays employ a labelled antibody. In such an assay, the amount of labelled antibody associated with ~,~," --1--~28~640 the complex is proportional to the amount of antigenic substance in the fluid sample.
Immunometric assays have been found to be particu-larly well suited for the detection of polyvalent anti-gens, i.e., antigenic substances that are able to complex with two or more antibodies at the same time. Such assays typically employ a quantity of unlabelled antibody bound to a solid support that is insoluble in the fluid being tested and a quantity of soluble antibody bearing a lO label such as a radioactive isotope that permits detec-tion and/or a quantitative estimate of the amount of the ternary complex formed between solid phase antibody, antigen, and labelled antibody.
In immunometric assays known to the prior art, typically "forward" a~sayæ, in which the antibody bound to the solid phase is first contacted with the sample being tested to extract the antigen from the sample by formation of a binary solid phase antibody: antigen complex, are employed. After a suitable incubation 20 period, the solid support is washed to remove the residue of the fluid sample, including unreacted antigen, if any, and then contacted with a solution containing a known quantity of labelled antibody.
After a second incubation period to permit the labelled antibody to complex with the antigen bound to the solid support through the unlabelled antibody, the solid support is washed a second time to remove the unreacted labelled antibody. In a simple "yes/no" assay to determine whether the antigen is present in the sample 30 being tested, the washed solid support is tested to ~Z8~6~D
detect the presence of labelled antibody, for example, by measuring emitted radiation if the label is a radioactive element. The amount of labelled antibody detected is compared to that for a negative control sample known to be free of the antigen. Detection of labelled antibody in amounts substantially above the background levels indicated by the negative control is interpreted to indicate the presence of the suspect antigen. Quanti-tative determinations can be made by comparing the 10 measure of labelled antibody with that obtained for calibrated samples containing known quantities of the antigen.
This kind of assay is frequently referred to as a "two-site" or "sandwich" assay since the antigen has two antibodies bonded to its surface at different loca-tions. This and related techniques are described by Wide at pp. 199-206 of "Radioimmunoassay Methods, n Edited by Kirkham and Hunter, E. & S. Livingstone, Edinburgh, 1970. An assay based on this technique for the detection 20 of the antigen associated with serum hepatitis using an 5I labelled antibody is described in U.S. Patent 3,867,517.
Despite their great utility, the prior art immuno-,:
~ metric assays have been recognized to be slow procedures, :: :
in part because two washing steps are required andbecause lengthy incubation periods are required to approach equilibrium, i.e., the point at which the amount ~;~ of complex formed does not change with increasing time.
To eliminate at least one of the washing steps 30 associated with this procedure, so-called "simultaneous"
:: .
~ -3-6~0 and "reverse" assays have been proposed. A simultaneous assay involves a single incubation step as the antibody bound to the solid support and the labelled antibody are both added to the sample being tested at the same time.
After the incubation is completed, the solid support is washed to remove the residue of fluid sample and uncom-plexed labelled antibody. The presence of labelled antibody associated with the solid support is then determined as it would be in a conventional "forward"
10 sandwich assay.
A reverse assay involves the stepwise addition first of a solution of labelled antibody to the fluid sample followed by the addition of unlabelled antibody bound to a solid support after a suitable incubation period. After a second incubation, the solid phase is washed in conventional fashion to free it of the residue of the sample being tested and the solution of unreacted labelled antibody. The determination of labelled anti-body associated with the solid support is then determined 20 as in the simultaneous and forward assays.
Both the simultaneous and reverse assay techniques require a sufficient excess amount of solid phase anti-body to bind most or all of the antigen present to avoid a high dose hook effect where artifically negative or low quantitation of antigen is observed at extremely high concentrations of antigen. For this reason, the forward assay has been the approach preferred by the prior art.
That is because ward assay has been the approach prefer-red by the prior art. That is because large amounts of 30 highly purified, active antibody specific to the antigen ~8~640 of interest for preparing a solid phase with sufficient antigen binding capacity is difficult to obtain from the "polyclonal" antibodies used in prior art processes.
When an immunogenic substance is introduced into a living body, the body's immune system reacts by generating antibodies to every site on the immunogen it recognizes.
A large immunogenic protein molecule may have dozens of sites and a foreign cell may have hundreds. Thus, while each antibody producing cell produces antibody specific 10 for a single antigenic site the immune system has genera-ted a specie of specific antibody producing cells for each immunogenic site recognized. In addition, the body has produced relatively large quantities of antibodies to antigens other than the one of interest such that most of the antibody in the polyclonal mixture is not specific for the antigen of interest. Accordingly, the antibodies used in prior immunometric assays are necessarily "poly-clonal n in nature since the antibodies are derived from antisera raised in a conventional manner in animals and 20 their purification is difficult. Methods for affinity purifying such antibodies have generally been time consuming and resulted in low yields and loss of high affinity antibodies.
When employing conventional polyclonal antibody mixtures in the reverse and simultaneous assays, the formation of a "sandwich" comprising the antigen com-plexed by two or more labelled antibodies which complex with the antigen at dlfferent sites is possible. These complexes could remain soluble in the sample being 30 tested, be removed by subsequent washing steps, and not : : :
1~816~0 "counted" when the solid phase is analyzed for solid phase bound labelled antibody. If this happens to a significant extent, sensitivity of the assay is reduced and erroneous results may arise. However, if the unla-belled bound antibody is added to the sample first as in the forward sandwich assay, steric considerations prevent formation of a sandwich comprising the antigen complexed to two or more unlabelled antibodies where labelled antibody is excluded from also binding to the 10 antigen. Accordingly, the antigen is free to react with a labelled antibody molecule. Nevertheless, it has been proposed to use a simultaneous assay for human thyroid stimulating hormone (HTSH) by employing a large excess of the unlabelled antibody bound to a solid phase to mini-mize formation of a soluble complex by soluble labelled antibodies. See Jeong et al., "Comparison of Radioim-munoassay (RIA) with a Unique, Single-Incubation Two-Site Immunoradiometric Assay (IRMA) as Applied to the Deter-mination of Human Thyroid Stimulating Hormone (HTSH),"
20 Bio-Rad Laboratories, 1979.
A variation of a simultaneous assay is described in U.S. 4,174,384. In that assay, separate portions of AntiIgG (Human) are labelled, respectively, with a fluorescing chromophore (fluorescein) and a chromophore (rhodamine) which absorbs light emitted by the fluo-rescein. Both antibodies, in a soluble form, are con-tacted with a sample containing human IgG. Reaction of the Anti-IgG with the IgG may bring the two chromophores close enough together, i.e., within 100 angstroms or 30 less, that the emission of light by the fluorescing 6~0 chromophore is absorbed (quenched) by the other. The percentage of maximum fluorescence for the sample is determined and used as a measure of the amount of IgG in the sample.
It has also been proposed to use a reverse assay for HTSH, hepatitis associated antigen (HA~) and car-cinoembryonic antigen (CEA) by employing a quantity of labelled antibody sufficient to assure a labelled anti-body: antigen complex but insufficient to form a "sand-10 wich" of all the antigen present in a sample. See U.S.Patent No. 4,098,876.
Since all three of the procedures known to the prior art use a polyclonal mixture of antibodies, the potential for cross-reaction with other materials in serum or other fluid than the antigen for which the test is intended is increased. The occurrence of cross-re-activity with other antigens also reduces the sensitivity of the test for the suspect antigen and increases the prospect of a "false-positive" assay. Furthermore, the 20 use of polyclonal antibodies in a simultaneous or reverse ~ assay requires a careful consideration of the amount of labelled antibody used relative to the amount of solid phase antibody and/or antigen present. In the case of using fluorescence quenching, sensitivity is reduced because the minimum spacing between the fluorescing chromophore and the quenching chromophore is not assured when polyclonal antibodies are employed.
In view of these shortcomings, the limitations to the immunometric procedures known to the prior art are 30 readily apparent. The conventional forward assays are ; -7-lZ8~0 accomplished with fewer steps but require large quanti-ties of solid phase specific antibody and are not well suited to determination of small concentrations of antigen since formation of a sandwich of the antigen with a multiple number of labelled antibody molecules competes with formation of the sandwich comprising bound antibody:antigen:labelled antibody or, in the case of using fluorescence quenching, the formation of a sand-wich without pairing of a fluorescent chromophore with a quenching chromophore is possible; and all are subject to misinterpretation of false-positives due to the polyclonal nature of the antibody.
Accordingly, the present invention is directed towards the provision of an improved process for the immunometric assay for antigenic substances, which permits more rapid immunometric assay techniques and more sensitive immunometric assay techniques.
With the present invention, the polyclonal anti-bodies used in an immunometric assay, for example, as the unlabelled antibody bound to a solid support and the antibody used as the soluble labelled antibody or, in the case of assays relying upon fluorescence quenching, the antibodies carrying a fluorescing or quenching chromophore are replaced by two or more monoclonal antibodies.
According to one aspect of the invention, there is provided an improvement in an immunometric assay process .
. - .
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~2~3~6~0 to determine the presence or concentration of an anti-genic substance in a fluid sample comprising forming a ternary complex of the antigenic substance, a first antibody and a second antibody bound to the antigen at a different site than the first antibody by contacting the sample with said first and second antibodies, the improvement comprising employing a monoclonal antibody for each of said first and second antibodies.
In a preferred embodiment of the invention, the monoclonal antibody used as the antibody bound to a solid support is the product of a different cell line than is the monoclonal antibody used for the labelled antibody and the two monoclonal antibodies are selected to bind the antigenic substance at sitee remote from each other so a~ to not interfere with the other's binding to the antigen. In the case of fluorescence quenching, the two antibodies are also usually the products of different cell lines and are selected so as to not interfere with the other's binding yet bring the two chromophores close enough together to permit quench-ing of fluorescence, i.e., usually to within about 100 angstroms. The advantages of the present invention, particularly in simultaneous and reverse assays, over prior art methods will become clear after consideration of the accompanying drawings and the following detailed description of the invention.
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, 16~0 Also, according to the present invention, monoclon-al antibodies are employed in inhibition assays. In such assays, a known quantity of an antigen and mono-clonal antibody is contacted with a sample suspected of containing an antigen corresponding to the known antigen added within the monoclonal antibody. The extent to which inhibition of the complex between the antibody and antigen occurs because a complex comprising the monoclonal antibody and antigen from the sample is formed is a measure of the presence and/or amount of antigen in the sample assayed.
Further, according to another aspect of the inven-tion, there is provided a process for the determination of the presQnce or concentration of an antig~nic substancQ in a fluid, comprising the stQps of:
(a) contacting a sample of the fluid with a known quantity o~ added antigenic substance and a monoclonal antibody to the antigenic substance, and ~ b) measuring the inhibition of formation of a complex between the antibody and added antigenic sub-stance by combination of said monoclonal antibody and the antigenic substance in the fluid to form a second complex.
In a preferred embodiment, the antibody and antigen are bound, respectively, to one of the members of a pair of fluorescing and quenching chromophores. Inhibition of the formation of a complex between the labelled ~:
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--antigen and antibody by antigens in the sample being assayed leads to a reduction in quenching and an increase in fluorescence. The extent of the inhibition of quenching is a measure of antigen concentration in the sample. In another preferred embodiment of an inhibition assay, the known antigen and antibody the original compLex are bound to particles, for example, latex particles, of a size which permits agglomerates to form. When a sample suspected of containing antigen is contacted with the antibody and bound antigen, inhibi-tion of agglomerate formation occurs because of complex-ing between the bound antibody and sample antigen which cannot form agglomerates. The reduction in agglomera-tion can be measured using turbidimetric techniques.
According to a further aspect of the invention, there i~ provided a process for the determination of the presence or concentration of an antigenic substance in a fluid, comprising the steps:
(a) contacting a sample of the fluid with a soluble first monoclonal antibody to the antigenic substance in order to form a soluble complex of the antibody and antigenic substance present in the sample, the first monoclonal antibody being labelled;
(b) contacting the soluble complex with a second monoclonal antibody bound at the time of the determin-ation to a solid carrier, the solid carrier being insoluble in the fluid, in order to form an in~oluble ., - .
: . . . . .
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l2a~640 lla complex of the first monoclonal antibody, the antigenic substance and the second monoclonal antibody bound to the 801 id carrier;
(c) separating the solid carrier from the fluid sample and unreacted labelled antibody;
(d) measuring either the amount of labelled anti-body associated with the solid carrier or the amount of unreacted labelled antibody; and (e) relating the amount of labelled antibody measured with the amount of labelled antibody measured for a control sample prepared in accordance with steps (a)-(d), the control sample being Xnown to be free of the antigenic substance, to determine the presence of antigenic substancQ in the fluid sample, or relating : 15 the amount of labelled antibody measured with the amount o~ labelled antibody mQasured for samples containing known amounts of antigenic substance prepared in accor-dance with steps (a)-(d) to determine the concentration : of antigenic substance in the fluid sample.
-: 20 According to an additional aspect of the invention, there is provided a process for the determination of the presence of an antigenic substance in a fluid comprising the steps:
a) simultaneously contacting a sample of the .::
~: 25 fluid with first and second monoclonal antibodies to the antigenic substance, the first monoclonal antibody ,~ being labelled and the second monoclonal antibody being 'i~
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llb bound at the time of the determination to a solid carrier insoluble in the fluid, in order to form an insoluble complex of the first monoclonal antibody, the antigenic substance and the second monoclonal antibody;
b) separating the solid carrier from the fluid sample and unreacted labelled antibody;
c) measuring either the amount of labelled antibody associated with the solid carrier or the amount of unreacted labelled antibody; and d) relating the amount of labelled antibody measured with the amount of labelled antibody measured for a control sample prepared in accordance with steps (a)-(c), the control sample being known to be free of the antigenic substance, to determine the presence of antigenic substance in the fluid sample, or relating the amount of labelled antibody measured with the amount of labelled antibody measured for samples containing known amounts of antigenic substance prepared in accor-dance with steps (a)-(d) to determine the concentration of antigenic substance in the fluid sample.
In a yet further aspect of the present invention, there is provided an improvement in an immunometric assay for the determination of the presence or concen-tration of an antigenic substance in a sample of a fluid comprising forming a ternary complex to a first labelled antibody, the antigenic substance, and a second antibody, the second antibody being bound at the ! I ~
~ ~r ~z~
llc time of the determination to a carrier insoluble in the fluid, the improvement comprising employing a mono-clonal antibody for each of the labelled antibody and the antibody bound to a solid carrier.
The present invention also includes a kit for effecting an immunometric assay and, accordingly, yet another aspect of the invention provides an improvement in an immunometric assay kit for the determination of the presence or concentration of an antigenic substance lo in a sample of a fluid comprising reagents for forming a ternary complex to a first labelled antibody, the anti-genic substance, and a second antibody, the second antibody being bound at the time of the determination to a carrier in~oluble in the ~luid, the improvement comprising employing a monoclonal antibody for each of the labelled antibody and the antibody bound to a solid carrier.
Further, the present invention provides a reagent for immunological assay of antigens based on the sand-, - 20 wich method, characterized in that it comprises insolubilized monoclonal antibody and labelled mono-clonal antibody, the monoclonal antibodies respectively being capable of distinguishing and binding to different ~ antigen determinants of an antigen to be assayed.
`~ 25 Additionally, the present invention provides an improved sandwich method for immunolo~ical assay of - antigens wherein the improvement resides in the fact -: . . .
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lld that insolubilized antibody and labelled antibody react simultaneously with an antigen to be assayed, the insolubilizQd antibody and labelled antibody comprising monoclonal antibodies capable of distinguishing and respectively binding to different antigen determinants of the antigen.
Yet further, the present invention provides an improved sandwich method for immunological assay of antigens wherein the improvement resides in the fact that insolubilised antibody and labelled antibody react simultaneously or in several incubation steps with an antigen to be assayed, the insolubilized antibody and labelled antibody comprising monoclonal antibodies capable of distingui~hlng and re~pectively binding to di~ferent antigen determinants of the antigen.
Yet another aspect of the present invention pro-vides a mixture of monoclonal antibodies useful in an enhanced sensitivity assay for detecting an antigen in a sample which comprises an effective assaying amount of each of at least two monoclonal antibodies which bind to different antigenic sites on the antigen and which are capable under appropriate conditions of forming a stable complex which includes the antigen and all of the -~ monoclonal antibodies.
In each of the various aspects of the invention as recited above, it is preferred that each of the mono-~; clonal antibodies ha~ an affinity for the antigen of at ,:~
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~281640 lle least about lo8 liters/mole and, more preferably an affinity of at least about lO9 liters/mole.
In the Examples which appear below, reference is made to the accompanying drawings, wherein:
Fig. 1 is a graph illustrating the results obtained using polyclonal antibodies in four types of immuno-metric assay for human IgE: and Fig. 2 is a similar graph illustrating the differ-ence in results obtained using monoclonal antibodies in the same four types of immunometric assay for human IgE.
As indicated above, according to the present invention, the polyclonal antibody used in an immuno-metric assay for an antigenic substance is replaced by a monoclonal antibody. Similarly, monoclonal antibodies are used in inhibition assays. The present invention is -- -- -: - ~ . . ,-, - ~: , .- - ~
.
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useful for the determination of the presence and concen-tration of a wide variety of antigenic substances in-cluding polyvalent antigenic substances. Accordingly, as used herein, the term antigen or antigenic substance refers broadly to substances to which antibodies can be produced. Among such substances may be mentioned hap-tens, hormones such as insulin and human thyroid stim-ulating hormone (HTSH), gamma globulins, allergens, viruses, virus subunits, bacteria, toxins such as those 10 associated with tetanus and with animal venoms, and even some drugs. Among the specific antigens which may be assayed by the processes of the present invention may be mentioned carcinoembryonic antigen (CEA), hepatitis A and B, hepatitis Non A - Non B, IgE and alphafetoprotein.
The monoclonal antibodies useful in the present invention are obtained by the process discussed by Milstein and Kohler and reported in Nature 256 495-497, 1975. The details of this process are well known and will not be repeated here. However, basically it in-20 volves injecting a mouse, or other suitable animal, withan immunogen. The mouse is subsequently sacrificed and cells taken from its spleen are fused with myeloma cells. The result is a hybrid cell, referred to as a "hybridoma, n that reproduces in vitro. The population of hybridomas is screened and manipulated so as to isolate individual clones each of which secretes a single anti-body species to the antigen. Each individual antibody species obtained in this way is the product of a single cell from the immune animal generated in response to a ~ .
~ ~ .
1~
specific antigenic site recognized on the immunogenic substance.
When an immunogenic substance is introduced into a living host, the host's immune system responds by producing antibodies to all the recognizable sites on the substance. This "shotgun" approach to producing anti-bodies to combat the invader results in the production of antibodies of differing affinities and specificities for the immunogenic substance. Accordingly, after the 10 different hybridoma cell lines are screened to identify those that produce antibody to the desired antigen, the antibodies produced by the individual hybridoma cell lines are preferably screened to identify those having the highest affinity for the immunogenic substance stimulating their original production before selection for use in the present invention. Selection based on this criterion is believed to help provide the increased sensitivity in the immunometric and inhibition assays of the present invention using monoclonal antibody compared 20 to the polyclonal antibody used in the prior art which, at best, has an affinity for the antigen which is roughly the average of the affinities of all antibodies produced by the immune system. Preferably, the monoclonal anti-body selected will have an affinity compatible with the desired sensitivity and range for the test system under consideration. Preferably the antibody will have an affinity oP at least 108 liters/mole and, more prefer-ably, an affinity of at least about lO9 liters/mole.
Furthermore, those monoclonal antibodies having 30 the highest affinities can be further screened by running :::
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a simulated assay on specimens known to give false positive-results with processes employing conventional polyclonal antibodies to identify those monoclonal antibodies which do not cross-react and give false positive results.
8ecause the two-site immunometric assay relies upon formation of an antibody:antigen:antibody sandwich, -usually two different monoclonal antibodies which do not interfere with the binding of each other to the antigen 10 are selected to be the bound antibody and the soluble labelled antibody or the antibody pair when fluorescence ~uenching is used. Since both are necessary to complete the sandwich, reverse and simultaneous assays can be conducted without concern, for example, that a complex of labelled antibody:antigen:labelled antibody will form which will preclude formation of a complex between the antigen and the antibody bound to the solid phase and therein lies a particular advantage of the present invention. Furthermore, a forward assay can be accom-20 plished without the intermediate washing step since thetwo antibodies bind to two different sites. We refer to such a process as a "fast forward" assay.
However, particularly in the case of a forward assay, the same monoclonal antibody can be used for both ~ the labelled antibody and the antibody b~und to the solid ;~ support when the antigenic substance possesses identical antibody binding sites sufficiently remote from each ~; other to allow more than one antibody molecule to be bound at the same time. In such a system, the addition 30 first of the bound antibody to the sample precludes ~8164~
formation of a sandwich because of steric considera-tions. When the labelled monoclonal antibody is sub-sequently added, it is also able to complex with the antigen bound to unlabelled antibody on the solid phase.
The unlabelled monoclonal antibody used in the process of the present invention to extract the antigenic substance from the sample being tested may be immobilized on any of the common supports used in immunometric assays. Among these may be mentioned filter paper, 10 plastic beads or test tubes made from polyethylene, polystyrene, polypropylene or other suitable material.
Also useful are particulate materials such as agarose, cross-linked dextran, and other polysaccharides.
The techniques for bonding antibodies to such materials are well know to those skilled in the art. For example, antibodies may be bound to polysaccharide polymers using the process described in U.S. Patent No. 3,645,852.
The labelled monoclonal antibody used in the present invention may be provided with the same labels used in 20 prior art immunometric assays. ~mong these may be mentioned fluorogenic labels for detection by fluorimetry as described in U.S. Patent No. 3,940,475 and enzymatic markers as described in U.S. Patent No. 3,654,090. It is presently preferred to label the antibody with a radioiso-tope such as 125I using, for example, the procedure of Hunter and Greenwood, Nature, 144 (1962), page 945 or that of David et al., Biochemistry, Vol. 13, pp.
1014-1021, 1974.
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In a typical assay, the amount of labelled antibody associatPd with the insoluble sandwich complex is deter-mined by examination of the insoluble carrier material by suitable means. However, it is also possible to relate the presence or absence of antigen in the fluid sample being assayed to the amount of labelled antibody which does not react during the assay and remains in soluble form.
The advantages of the present invention in which 10 monoclonal antibodies are used in immunometric assays as compared to polyclonal antibodies are seen by reference to the following example. In this example, four com-parative assays, a simultaneous assay, a reverse assay, a forward assay, and a "fast" forward assay, were run using both monoclonal antibody and polyclonal antibody using a standard serum containing 100 IU/ml of human IgE as the positive sample. Normal horse serum containing no IgE
was used as a negative control.
The polyclonal antibody to IgE used as the labelled 20 antibody in the example was obtained from Pharmacia Diagnostics of Piscataway, New Jersey. The polyclonal antibody bound to the solid support was obtained from Tago, Inc. of Burlingame, California.
Monoclonal antibody to IgE was obtained using the method of Milstein and Kohler discussed above. The two antibodies selected each exhibited an affinity for IgE of greater than 109 liters/mole and did not interfere :
with the other's binding to IgE.
The assays were run using unlabelled antibody bound 30 to agarose by the process of U.S. Patent No. 3,645,852.
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Labelling of antibody was by 125I according to the process of David et al. referred to above. Phosphate buffered saline, pH 7.4, was used to wash all samples.
Example 1) Simultaneous Assay Method -Duplicate samples were run in which 100 ~ of a suspension of antibody immobilized on agarose particles was mixed with 100 ~ of specimen (serum) and 100 ~ of soluble 25I-labelled antibody. This mixture was incubated 10 for the specified times shown in Table I (for polyclonal antibody) and Table II (for monoclonal antibody) set forth below, plus 30 minutes. The extra 30 minutes incubation period was added to equalize this assay method with the other assay methods which required an additional 30 minutes incubation time for a second added reagent.
Following the incubation periods the agarose particles were washed by addition of buffer and centrifuged. After removal of the washing liquid by aspiration, the re-sulting pellet of agarose particles was then counted for 20 bound 125I-labelled antibody. The counts obtained for each of the complexes after the specified incubation time are set forth in Tables I and II.
2) Reverse Assay Method -Duplicate samples were run in which 100 ~ of specimen (serum) was mixed with 100 ~ of 125I-labelled soluble antibody and incubated for the specified times shown in Tables I and II. 100 ~ of a suspension of antibody immobilized on agarose particles is then added and the mixture was allowed to incubate for another 30 minutes.
30 The agarose particles were then washed and counted as in ~:
~28~
the simultaneous assay method. The counts are reported in Tables I and II.
30 The agarose particles were then washed and counted as in ~:
~28~
the simultaneous assay method. The counts are reported in Tables I and II.
3) Forward Assay Method -Duplicate samples were run in which 100 ~ of specimen (serum) was mixed with 100 ~ of a suspension of antibody immobilized on agarose particles and incubated for the specified times shown in Tables I and II. The agarose particles were then washed once by the addition of 2.5-3.0 ml of buffer which, after mixing, was centri-10 fuged, and the liquid removed by aspiration. 100 ,ulof I-labelled soluble antibody was then added and the mixture incubated an additional 30 minutes. The agarose particles were then washed and counted as in the simultaneous assay method. The counts are reported in Tables I and II.
4) Fast Forward Assay Method -The assay was performed, in duplicate, in a similar manner to the forward assay method except that the wash step between the initial incubation of specimen with 20 antibody immobilized on agarose particles and the addition of soluble 125I-labeled antibody was omit-ted.
The counts/minute for the duplicate controls and the duplicate assays of the samples containing IgE using polyclonal antibody and monoclonal antibody are shown in Tables I and II, respectively. These data were used to prepare Figures I and II in the following way. The average of the counts/minute for a control for a given incubation period was subtracted from the average of the ~; 30 counts for the corresponding IgE assay. The difference , was calculated as a percentage of the total counts/
minute of labelled antibody added to the sample and is plotted on the Y axis as the percentage of total counts/
minute of antibody bound to the solid phase. The incuba-tion time is plotted on the X axis.
A comparison of the plots shown in Figure 2 dis-playing the results of assays using monoclonal antibody with those of Figure 1 of assays using using polyclonal antibody shows that in êach kind of assay, simultaneous, 10 reverse, forward, and fast forward, the assay using monoclonal antibody was more sensitive as indicated by the higher percentage of total counts bound to the solid phase with 100 IU IgE/ml specimen. Unexpectedly, in the case of the simultaneous and reverse assays, we have found that those run with monoclonal antibody reach equilibrium more rapidly than does the corresponding assay using polyclonal antibody. Therefore, by using a monoclonal antibody in these procedures, the time for the assay can be reduced significantly beyond the time saving 20 achieved by merely eliminating a washing step. In that regard, the reverse assay with monoclonal antibody reached equilibrium in less than one hour. The same assay run with polyclonal assay did not reach eguilibrium until after 4 hours. Similarly, in the case of simulta-neous assays, the assay using monoclonal antibody reached equilibrium within 8 hours whereas the assay with poly-clonal antibody did not reach equilibrium within 24 hours. Accordingly, the present invention provides substantially more rapid and sensitive simultaneous and reverse assays than the prior art processes and elimi-nates the concern that formation of a soluble "sandwich"
complex will compete with formation of the desired insoluble complex.
In the foregoing discussion, the focus has been upon two site or sandwich assays in which one of the antibodies is insolubilized while the other is soluble in the medium analyzed. Other variations are possible. A
preferred variant employs antibodies bound to particles, 10 such as particles of latex, in a manner which results in each particle carrying a plurality of antibodies. When a quantity of particles to which a first monoclonal anti-body is bound is admixed with, for example, quantity of particles to which a second monoclonal antibody is bound, a milky suspension results. However, if a sample con-taining polyvalent antigen for which the antibodies are specific is introduced to the suspension, agglomeration or agglutination of the particles will occur to form easily detectable particle clumps.
The visual detection of agglomerate formation can be used in a screening test for presence of the antigen.
This detection can be aided by coloring the particles carrying one monoclonal antibody differently from the particle carrying the other. However, the extent of agglomeration can also be determined as a measure of the amount of antigen present in the sample. For example, the change in turbidity can be measured using standard techniques such as nephelometry.
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128~640 It is presently preferred to use latex particles to which the antibody is covalently bound using techniques well known to those skilled in the art. However, other particulate supports can be used. Among these may be mentioned silica, glass, cells, polyacrylamides, poly-methyl methacrylate and agarose. Preferably, the par-ticles vary in size between about 0.2~ to about 10~.
Visual screening, however, requires particles of at least about 1.0~.
In yet another variant, one of the antibodies is insolubilized on a bead, test tube wall or other macro-scopic solid suport, and the other is bound to small particles of latex or other suitable material. In the presence of antigen, a sandwich of the antigen between the macroscopically bound antibody and the particle bound antibody will form. By, for example, coloring the particles, formation of the sandwich can be determined visually. A fluorescent, enzymatic, radioactive or other label on the particle bound antibody can be used for 20 quantitative determinations just as in the case of using a soluble antibody described above.
In another preferred variant of the two-site assay, at least one of two different monoclonal antibodies is bound to an enzyme which catalyzes a reaction involving a substance bound to the other monoclonal antibody to produce either a detectable substance or in some other way interacts with the substance on the second antibody to permit detection of the antibody:antigen:antibody complex. Detection may be, for example, by colorimetry, 30 fluorimetry, luminescence, spectrophotometry, or the :, .
12816~0 like. It will be appreciated that, using such techniques, neither antibody needs to be insolubilized, greatly simplifying the assay.
In a presently preferred embodiment, the substance on the second antibody is also an enzyme and the assay employs the pair of enzyme labelled antibodies to cat-alyze sequential reactions, one of which produces a product required by the other. In those reactions, the two antibodies are selected so that when they bind with 10 the antigen, they are sterically positioned so that the product of the first enzymatic reaction is generated in such close proximity to the second enzyme labelled antibody, that the second reaction occurs before signif-icant diffusion of the product of the first reaction into the surrounding medium can take place.
This process can be illustrated using a pair of monoclonal antibodies, one of which is labelled with hexokinase (HK), the other with glucose-6-phosphate dehydrogenase (G-6-PDH), in the following series of 20 reactions.
HK
(1) adenosine triphosphate + glucose r (ATP) adenosine diphosphate + glucose-6-phosphate (ADP) 1~8~6~0 (2) glucose-6-phosphate + nicotinamide adenine dinucleotide (NAD+) ~ gluconolactone-6-phosphate +
dihydronicotinamide adenine dinucleotide (NADH) The assay is conducted by adding to the sample containing the suspect antigen the labelled antibodies to 10 the antigen, ATP, glucose and the coenzyme NAD+. If the antigen is present, a complex as illustrated below is formed:
- Ab(~K) Ag - Ab(G-6-PDH) The HK labelled antibody catalyzes the formation of glucose-6-phosphate in proximity to the G-6-PDH labelled antibody where it is converted to gluconolactone-6-phos-phate. The NADH formed in this reactio~ by reduction of 20 NAD+ can be detected spectrophometrically because of the strong absorption at 340 nm characteristic of a dihydronicotinamide.
The same conversion of glucose to gluconolactone-6-phosphate with formation of NADH also may occur in the medium itself catalyzed by the uncomplexed labelled antibodies, but at a much slower rate than when the two antibodies are positioned near each other in the anti-body:antigen:antibody complex. Accordingly, an increase of absorption at 340 nm compared to a control sample 30 confirms the presence of antigen in the sample. The ,, .
~2~
increase in absorption can also be corelated to the quantity of antigen in the complex.
Any other pair of suitable sequential enzymatically catalyzed reactions may be used in a two-site assay with appropriately labelled antibodies to a suspect antigen.
Among those may be mentioned the reaction of glucose catalyzed with glucose oxidase to form glucono-~-lactone and hydrogen peroxide followed by the reaction of the hydrogen peroxide with ophenylenediamine catalyzed by 10 peroxidase to produce a colored moiety. In this assay, one of the monoclonal antibodies is labelled with glucose oxidase and the other with peroxidase. The intensity of the color produced compared to a control can be corre-lated to the presence and/or amount of antigen in the sample assayed. It will be appreciated that other substances oxidizable to a colored moiety in the presence of an enzyme can be substituted for o-phenylenediamine.
Yet another suitable pair of sequential reactions using a pair of antibodies to a desired antigen labelled, 20 respectively, with NAD oxidoreductase and luciferase is the following:
NAD oxido-reductase (1) NADH + riboflavin-5'-phosphate (FMN) FMNH2 + NAD+
luciferase (2) FMNH2 + RCHO + 2 FMN* + RCOOH + H2O
RCHO is typically a straight chain aldehyde of 10 or more 30 carbon atoms.
.:
12816~0 The generation of FMN*, an excited state of FMN, is followed by the emission of a photon which can be detec-ted photometrically for correlation with a control sample to indicate the presence and/or quantity of antigen in a sample being assayed.
In another embodiment using a pair of antibodies labelled with enzymes, the product of the first enzymat-ically catalyzed reaction can be either an allosteric activator or inhibitor of the subsequent enzyme catalyzed 10 reaction. An allosteric activator, rather than being consumed in the second reaction, interacts with the enzyme to increase its affinity for a substrate or to increase the rate of conversion of the substrate to product after the enzyme-substrate complex is formed.
Allosteric inhibitors, on the other hand, have the opposite effect and reduce the enzyme's affinity for a substrate or reduce the rate of conversion of substrate to product. Allosteric inhibition may be of the compet-itive or non-competitive type.
An example of an assay involving allosteric activa-tion employing a pair of antibodies labelled, respec-tively, with phosphofructokinase and phosphoenolpyruvate uses the following reaction scheme:
phosphofructokinase (1) fructose-6-phosphate + ATP
fructose-1,6-diphosphate + ADP
12Bl~O
(2) HCO3- + phosphoenolpyruvate (PEP) phosphoenolpyruvate carboxylase - ~ oxaloacetate (OAA) malate dehydrogenase (3) OAA + NADH ~ malate + NAD+
The fructose-1,6-diphosphate formed in reaction (1) allosterically interacts with the phosphoenolpyruvate carboxylase and activates its catalysis of reaction (2), the formation of oxaloacetate from PEP. Reaction (3) occurs in the sureounding medium, i.e., there is no necessity to bind the malate dehydrogenase to a third monoclonal antibody. The presence and/or guantity of suspect antigen is determined by correlating the reduc-tion in the absorption at 340 nm by NADH which is oxidized in reaction (3) to NAD+.
An example of an assay involving allosteric inhibi-tion employing a pair of antibodies labelled, respect-fully, with aspartate amino transferase (AST) and phos-phoenolpyruvate carboxylase can use the following re-action scheme:
AST
(lj oxaloocetate + glutamate ~ aspartate +
-ketoglutorate phosphoenolpyruvate carboxylase 30 (2) PEP + NADH ~ OAA + NAD+
^` -28-;~ :
^ ~, 12t3~40 The aspartate formed in reaction (1) inhibits the second reaction by allosterically interacting with the phosphoenolpyruvate carboxylase. This reduces the rate at which NADH is oxidized to NAD+. Therefore, the decrease in the absorption at 340 nm exhibited by NADH
can be correlated to the presence and/or quantity of antigen in the sample being assayed, a smaller decrease than occurs with a control sample indicating that antigen is present.
Those skilled in the art will appreciate that numerous other reaction pairs involving activation or inhibition of the second enzymatically catalyzed reaction can be substituted for the examples set forth above for use in a two-site assay. In another embodiment, only one of the antibody pairs is labelled with an enzyme, the second being labelled with a substance, for example, that undergoes a reaction catalyzed by the enzyme to produce a second product which can be detected and/or quantified by colorimetric, fluorimetric, luminescence, spectrophoto-metric or other technique. One such example uses a pair of monoclonal antibodies, one of which is labelled with peroxidase and the other with luminol, and takes advan-tage of the following reaction:
N~2 , per~ tl 33 dase ~~o~
+ 2~02 ---~N2 ~ 2R20 J hv ~
: ;~ ' O
luminol , ~ -29-:~
1281~0 The photon (h~) emitted by the reaction can be detected using photometric techniques and related to the presence and/or quantity of an antigen in a sample being assayed.
In yet another preferred variant of the two-site assay, the two monoclonal antibodies are, respectively, conjugated with a fluorescing chromophore and a quenching chromophore which absorbs light at the wavelength emitted by the fluorescer. The two antibodies are selected so 10 that, when they combine with the antigen for which they are specific, the two chromophores are positioned close enough to permit the light emitted by the fluorescer to be absorbed by the other chromophore. Usually, this will place them within about 100 angstroms of each other and, preferably, within about 50 angstroms of each other. The selection of suitable antibodies can be done through a screening procedure in which a mixture of fluorescent and quencher labelled monoclonal antibodies are contacted with a sample containing a known quantity 20 of antigen. Reduction of fluorescence is indicative that the two chromophores are positioned closely enough together.
Using fluorescence quenching, it is unnecessary to insolubilize either of the two antibodies. Quan-titative measurements can be made simply by measuring the decrease in maximum fluorescence, i.e., the amount of fluorescense exhibited by a control sample free of any antigen or by comparing the fluorescence of the sample with that of control samples containing a known quantity 30 of antigen. However, fluorescent-quenching chromophore ~ .
pairs can also be used in combination with the particle agglomeration technique and in the technique whereby one of the antibodies is insolubilized by being bound to a solid support such as a test tube wall or bead, since pairing of the fluorescent-quenching chromophores will occur. A decrease in fluorescence again is in-dicative of the presence or amount of antigen in the sample.
Suitable fluorescing and quenching chromophores and techniques for conjugating them with antibodies are described in United States Patent No. 4,174,384. Presently, it is preferred to use fluorescein and rhodamine as the fluorescer and quencher chromophores, respectively.
In the preceding discussion of our invention, we have described techniques of fluorescence quenching in which antibody pairs carrying the necessary chromophores are caused to bond to an antigen, if present in the sample being analyzed, in a steric arrangement which permits the quenching chromophore to absorb light emitted by the fluorescent chromophore. Quantitative deterDina-tions of the amount of antigen present are made by measuring the decrease in maximum fluorescence.
These techniques are well suited to determining the presence of antigen in a sample over a wide range of concentration. However, the small decreases in fluo-rescence which are associated with low antigen concen-tration are hard to detect and measure accura~ely. By contrast, small increases in fluorescence are relatively easy to detect and measure accurately. Accordingly, in ::
~ - 31 -:
12~l0 another aspect of our invention, we prefer to exploit the inhibition of quenching and measure increases in fluo-rescence.
To accomplish this in an assay for a particular antigen, quantities of the antigen and monoclonal anti-body to the antigen are individually labelled with one or the other of the pair of fluorescent-quencher chromo-phores. The chromophore labelled antigen and antibody are then combined to form a complex in which the fluo-rescent chromophore is positioned so that the light it emits is absorbed by the quenching chromophore. To -achieve this the antigen may be labelled with the fluo-rescer and the antibody with the quencher or vice versa.
A sample suspected of containing the antigen being assayed is then contacted with the chromophore labelled antigen and antibody. After a suitable incubation period, fluorescence is measured. If antigen is present in the assayed sample, it inhibits, at least in part, the formation of a complex between the chromophore labelled antigen and the antibody by itself forming a complex with the monoclonal antibody. To the extent this occurs, the fluorescer chromophore is no longer positioned so that the light it emits is absorbed by the quenching chromo-phore. This results in an increase in fluorescence. The increase in fluorescence can be measured and related to the concentration of antigen in the sample undergoing analysis by comparison with the fluorescence exhibited by control samples free of antigen or containing known amounts of antigen.
,i i2~316~
From the foregoing, it will be apparent that the chromophore labelled antigen:antibody complex may be a soluble one. However, it is presently preferred to employ chromophore labelled antigen and monoclonal antibody which are bound to latex or other suitable particles, for example, those listed above, of a size that will form agglomerates when the complex is formed.
Particles varying in size from about 0.2 to about 10 p are usually suitable for this purpose. When an 10 unknown sample containing the suspect antigen is con-tacted with the agglomerate forming particles of antibody and antigen, inhibition of agglomeration will occur because of sample antigen combining with particle-bound antibody. An increase in fluorescence will result, since quenching can no longer occur, which can be detected and measured to correlate with the amount of antigen in the sample by comparison with the fluoresence observed for a sample containing a known quantity of antigen.
It is also within the scope of our invention to 20 employ bound antigen and particle bound monoclonal antibody in an assay that directly measures the inhi-bition of agglomeration. In this technique, neither the antigen nor antibody is labelled. When a sample con-taining antigen is contacted with the particles, inhibi-tion of agglomeration during the incubation period will occur. This results in, at least, a partial reduction in the agglomerate formation. The inhibition is detected using nephelometry or other techniques for measuring turbidity. The decrease in turbidity can be correlated 30 to the amount of antigen in the sample.
.:-~Z~16~
The foregoing description of the invention and the examples demonstrating the application of the invention to assays for IgE are but exemplary of the various ways the invention can be utilized. That other variations will be useful will be apparent to those skilled in the art. Therefore, the present invention is to be con-sidered limited only by the appended claims.
The counts/minute for the duplicate controls and the duplicate assays of the samples containing IgE using polyclonal antibody and monoclonal antibody are shown in Tables I and II, respectively. These data were used to prepare Figures I and II in the following way. The average of the counts/minute for a control for a given incubation period was subtracted from the average of the ~; 30 counts for the corresponding IgE assay. The difference , was calculated as a percentage of the total counts/
minute of labelled antibody added to the sample and is plotted on the Y axis as the percentage of total counts/
minute of antibody bound to the solid phase. The incuba-tion time is plotted on the X axis.
A comparison of the plots shown in Figure 2 dis-playing the results of assays using monoclonal antibody with those of Figure 1 of assays using using polyclonal antibody shows that in êach kind of assay, simultaneous, 10 reverse, forward, and fast forward, the assay using monoclonal antibody was more sensitive as indicated by the higher percentage of total counts bound to the solid phase with 100 IU IgE/ml specimen. Unexpectedly, in the case of the simultaneous and reverse assays, we have found that those run with monoclonal antibody reach equilibrium more rapidly than does the corresponding assay using polyclonal antibody. Therefore, by using a monoclonal antibody in these procedures, the time for the assay can be reduced significantly beyond the time saving 20 achieved by merely eliminating a washing step. In that regard, the reverse assay with monoclonal antibody reached equilibrium in less than one hour. The same assay run with polyclonal assay did not reach eguilibrium until after 4 hours. Similarly, in the case of simulta-neous assays, the assay using monoclonal antibody reached equilibrium within 8 hours whereas the assay with poly-clonal antibody did not reach equilibrium within 24 hours. Accordingly, the present invention provides substantially more rapid and sensitive simultaneous and reverse assays than the prior art processes and elimi-nates the concern that formation of a soluble "sandwich"
complex will compete with formation of the desired insoluble complex.
In the foregoing discussion, the focus has been upon two site or sandwich assays in which one of the antibodies is insolubilized while the other is soluble in the medium analyzed. Other variations are possible. A
preferred variant employs antibodies bound to particles, 10 such as particles of latex, in a manner which results in each particle carrying a plurality of antibodies. When a quantity of particles to which a first monoclonal anti-body is bound is admixed with, for example, quantity of particles to which a second monoclonal antibody is bound, a milky suspension results. However, if a sample con-taining polyvalent antigen for which the antibodies are specific is introduced to the suspension, agglomeration or agglutination of the particles will occur to form easily detectable particle clumps.
The visual detection of agglomerate formation can be used in a screening test for presence of the antigen.
This detection can be aided by coloring the particles carrying one monoclonal antibody differently from the particle carrying the other. However, the extent of agglomeration can also be determined as a measure of the amount of antigen present in the sample. For example, the change in turbidity can be measured using standard techniques such as nephelometry.
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128~640 It is presently preferred to use latex particles to which the antibody is covalently bound using techniques well known to those skilled in the art. However, other particulate supports can be used. Among these may be mentioned silica, glass, cells, polyacrylamides, poly-methyl methacrylate and agarose. Preferably, the par-ticles vary in size between about 0.2~ to about 10~.
Visual screening, however, requires particles of at least about 1.0~.
In yet another variant, one of the antibodies is insolubilized on a bead, test tube wall or other macro-scopic solid suport, and the other is bound to small particles of latex or other suitable material. In the presence of antigen, a sandwich of the antigen between the macroscopically bound antibody and the particle bound antibody will form. By, for example, coloring the particles, formation of the sandwich can be determined visually. A fluorescent, enzymatic, radioactive or other label on the particle bound antibody can be used for 20 quantitative determinations just as in the case of using a soluble antibody described above.
In another preferred variant of the two-site assay, at least one of two different monoclonal antibodies is bound to an enzyme which catalyzes a reaction involving a substance bound to the other monoclonal antibody to produce either a detectable substance or in some other way interacts with the substance on the second antibody to permit detection of the antibody:antigen:antibody complex. Detection may be, for example, by colorimetry, 30 fluorimetry, luminescence, spectrophotometry, or the :, .
12816~0 like. It will be appreciated that, using such techniques, neither antibody needs to be insolubilized, greatly simplifying the assay.
In a presently preferred embodiment, the substance on the second antibody is also an enzyme and the assay employs the pair of enzyme labelled antibodies to cat-alyze sequential reactions, one of which produces a product required by the other. In those reactions, the two antibodies are selected so that when they bind with 10 the antigen, they are sterically positioned so that the product of the first enzymatic reaction is generated in such close proximity to the second enzyme labelled antibody, that the second reaction occurs before signif-icant diffusion of the product of the first reaction into the surrounding medium can take place.
This process can be illustrated using a pair of monoclonal antibodies, one of which is labelled with hexokinase (HK), the other with glucose-6-phosphate dehydrogenase (G-6-PDH), in the following series of 20 reactions.
HK
(1) adenosine triphosphate + glucose r (ATP) adenosine diphosphate + glucose-6-phosphate (ADP) 1~8~6~0 (2) glucose-6-phosphate + nicotinamide adenine dinucleotide (NAD+) ~ gluconolactone-6-phosphate +
dihydronicotinamide adenine dinucleotide (NADH) The assay is conducted by adding to the sample containing the suspect antigen the labelled antibodies to 10 the antigen, ATP, glucose and the coenzyme NAD+. If the antigen is present, a complex as illustrated below is formed:
- Ab(~K) Ag - Ab(G-6-PDH) The HK labelled antibody catalyzes the formation of glucose-6-phosphate in proximity to the G-6-PDH labelled antibody where it is converted to gluconolactone-6-phos-phate. The NADH formed in this reactio~ by reduction of 20 NAD+ can be detected spectrophometrically because of the strong absorption at 340 nm characteristic of a dihydronicotinamide.
The same conversion of glucose to gluconolactone-6-phosphate with formation of NADH also may occur in the medium itself catalyzed by the uncomplexed labelled antibodies, but at a much slower rate than when the two antibodies are positioned near each other in the anti-body:antigen:antibody complex. Accordingly, an increase of absorption at 340 nm compared to a control sample 30 confirms the presence of antigen in the sample. The ,, .
~2~
increase in absorption can also be corelated to the quantity of antigen in the complex.
Any other pair of suitable sequential enzymatically catalyzed reactions may be used in a two-site assay with appropriately labelled antibodies to a suspect antigen.
Among those may be mentioned the reaction of glucose catalyzed with glucose oxidase to form glucono-~-lactone and hydrogen peroxide followed by the reaction of the hydrogen peroxide with ophenylenediamine catalyzed by 10 peroxidase to produce a colored moiety. In this assay, one of the monoclonal antibodies is labelled with glucose oxidase and the other with peroxidase. The intensity of the color produced compared to a control can be corre-lated to the presence and/or amount of antigen in the sample assayed. It will be appreciated that other substances oxidizable to a colored moiety in the presence of an enzyme can be substituted for o-phenylenediamine.
Yet another suitable pair of sequential reactions using a pair of antibodies to a desired antigen labelled, 20 respectively, with NAD oxidoreductase and luciferase is the following:
NAD oxido-reductase (1) NADH + riboflavin-5'-phosphate (FMN) FMNH2 + NAD+
luciferase (2) FMNH2 + RCHO + 2 FMN* + RCOOH + H2O
RCHO is typically a straight chain aldehyde of 10 or more 30 carbon atoms.
.:
12816~0 The generation of FMN*, an excited state of FMN, is followed by the emission of a photon which can be detec-ted photometrically for correlation with a control sample to indicate the presence and/or quantity of antigen in a sample being assayed.
In another embodiment using a pair of antibodies labelled with enzymes, the product of the first enzymat-ically catalyzed reaction can be either an allosteric activator or inhibitor of the subsequent enzyme catalyzed 10 reaction. An allosteric activator, rather than being consumed in the second reaction, interacts with the enzyme to increase its affinity for a substrate or to increase the rate of conversion of the substrate to product after the enzyme-substrate complex is formed.
Allosteric inhibitors, on the other hand, have the opposite effect and reduce the enzyme's affinity for a substrate or reduce the rate of conversion of substrate to product. Allosteric inhibition may be of the compet-itive or non-competitive type.
An example of an assay involving allosteric activa-tion employing a pair of antibodies labelled, respec-tively, with phosphofructokinase and phosphoenolpyruvate uses the following reaction scheme:
phosphofructokinase (1) fructose-6-phosphate + ATP
fructose-1,6-diphosphate + ADP
12Bl~O
(2) HCO3- + phosphoenolpyruvate (PEP) phosphoenolpyruvate carboxylase - ~ oxaloacetate (OAA) malate dehydrogenase (3) OAA + NADH ~ malate + NAD+
The fructose-1,6-diphosphate formed in reaction (1) allosterically interacts with the phosphoenolpyruvate carboxylase and activates its catalysis of reaction (2), the formation of oxaloacetate from PEP. Reaction (3) occurs in the sureounding medium, i.e., there is no necessity to bind the malate dehydrogenase to a third monoclonal antibody. The presence and/or guantity of suspect antigen is determined by correlating the reduc-tion in the absorption at 340 nm by NADH which is oxidized in reaction (3) to NAD+.
An example of an assay involving allosteric inhibi-tion employing a pair of antibodies labelled, respect-fully, with aspartate amino transferase (AST) and phos-phoenolpyruvate carboxylase can use the following re-action scheme:
AST
(lj oxaloocetate + glutamate ~ aspartate +
-ketoglutorate phosphoenolpyruvate carboxylase 30 (2) PEP + NADH ~ OAA + NAD+
^` -28-;~ :
^ ~, 12t3~40 The aspartate formed in reaction (1) inhibits the second reaction by allosterically interacting with the phosphoenolpyruvate carboxylase. This reduces the rate at which NADH is oxidized to NAD+. Therefore, the decrease in the absorption at 340 nm exhibited by NADH
can be correlated to the presence and/or quantity of antigen in the sample being assayed, a smaller decrease than occurs with a control sample indicating that antigen is present.
Those skilled in the art will appreciate that numerous other reaction pairs involving activation or inhibition of the second enzymatically catalyzed reaction can be substituted for the examples set forth above for use in a two-site assay. In another embodiment, only one of the antibody pairs is labelled with an enzyme, the second being labelled with a substance, for example, that undergoes a reaction catalyzed by the enzyme to produce a second product which can be detected and/or quantified by colorimetric, fluorimetric, luminescence, spectrophoto-metric or other technique. One such example uses a pair of monoclonal antibodies, one of which is labelled with peroxidase and the other with luminol, and takes advan-tage of the following reaction:
N~2 , per~ tl 33 dase ~~o~
+ 2~02 ---~N2 ~ 2R20 J hv ~
: ;~ ' O
luminol , ~ -29-:~
1281~0 The photon (h~) emitted by the reaction can be detected using photometric techniques and related to the presence and/or quantity of an antigen in a sample being assayed.
In yet another preferred variant of the two-site assay, the two monoclonal antibodies are, respectively, conjugated with a fluorescing chromophore and a quenching chromophore which absorbs light at the wavelength emitted by the fluorescer. The two antibodies are selected so 10 that, when they combine with the antigen for which they are specific, the two chromophores are positioned close enough to permit the light emitted by the fluorescer to be absorbed by the other chromophore. Usually, this will place them within about 100 angstroms of each other and, preferably, within about 50 angstroms of each other. The selection of suitable antibodies can be done through a screening procedure in which a mixture of fluorescent and quencher labelled monoclonal antibodies are contacted with a sample containing a known quantity 20 of antigen. Reduction of fluorescence is indicative that the two chromophores are positioned closely enough together.
Using fluorescence quenching, it is unnecessary to insolubilize either of the two antibodies. Quan-titative measurements can be made simply by measuring the decrease in maximum fluorescence, i.e., the amount of fluorescense exhibited by a control sample free of any antigen or by comparing the fluorescence of the sample with that of control samples containing a known quantity 30 of antigen. However, fluorescent-quenching chromophore ~ .
pairs can also be used in combination with the particle agglomeration technique and in the technique whereby one of the antibodies is insolubilized by being bound to a solid support such as a test tube wall or bead, since pairing of the fluorescent-quenching chromophores will occur. A decrease in fluorescence again is in-dicative of the presence or amount of antigen in the sample.
Suitable fluorescing and quenching chromophores and techniques for conjugating them with antibodies are described in United States Patent No. 4,174,384. Presently, it is preferred to use fluorescein and rhodamine as the fluorescer and quencher chromophores, respectively.
In the preceding discussion of our invention, we have described techniques of fluorescence quenching in which antibody pairs carrying the necessary chromophores are caused to bond to an antigen, if present in the sample being analyzed, in a steric arrangement which permits the quenching chromophore to absorb light emitted by the fluorescent chromophore. Quantitative deterDina-tions of the amount of antigen present are made by measuring the decrease in maximum fluorescence.
These techniques are well suited to determining the presence of antigen in a sample over a wide range of concentration. However, the small decreases in fluo-rescence which are associated with low antigen concen-tration are hard to detect and measure accura~ely. By contrast, small increases in fluorescence are relatively easy to detect and measure accurately. Accordingly, in ::
~ - 31 -:
12~l0 another aspect of our invention, we prefer to exploit the inhibition of quenching and measure increases in fluo-rescence.
To accomplish this in an assay for a particular antigen, quantities of the antigen and monoclonal anti-body to the antigen are individually labelled with one or the other of the pair of fluorescent-quencher chromo-phores. The chromophore labelled antigen and antibody are then combined to form a complex in which the fluo-rescent chromophore is positioned so that the light it emits is absorbed by the quenching chromophore. To -achieve this the antigen may be labelled with the fluo-rescer and the antibody with the quencher or vice versa.
A sample suspected of containing the antigen being assayed is then contacted with the chromophore labelled antigen and antibody. After a suitable incubation period, fluorescence is measured. If antigen is present in the assayed sample, it inhibits, at least in part, the formation of a complex between the chromophore labelled antigen and the antibody by itself forming a complex with the monoclonal antibody. To the extent this occurs, the fluorescer chromophore is no longer positioned so that the light it emits is absorbed by the quenching chromo-phore. This results in an increase in fluorescence. The increase in fluorescence can be measured and related to the concentration of antigen in the sample undergoing analysis by comparison with the fluorescence exhibited by control samples free of antigen or containing known amounts of antigen.
,i i2~316~
From the foregoing, it will be apparent that the chromophore labelled antigen:antibody complex may be a soluble one. However, it is presently preferred to employ chromophore labelled antigen and monoclonal antibody which are bound to latex or other suitable particles, for example, those listed above, of a size that will form agglomerates when the complex is formed.
Particles varying in size from about 0.2 to about 10 p are usually suitable for this purpose. When an 10 unknown sample containing the suspect antigen is con-tacted with the agglomerate forming particles of antibody and antigen, inhibition of agglomeration will occur because of sample antigen combining with particle-bound antibody. An increase in fluorescence will result, since quenching can no longer occur, which can be detected and measured to correlate with the amount of antigen in the sample by comparison with the fluoresence observed for a sample containing a known quantity of antigen.
It is also within the scope of our invention to 20 employ bound antigen and particle bound monoclonal antibody in an assay that directly measures the inhi-bition of agglomeration. In this technique, neither the antigen nor antibody is labelled. When a sample con-taining antigen is contacted with the particles, inhibi-tion of agglomeration during the incubation period will occur. This results in, at least, a partial reduction in the agglomerate formation. The inhibition is detected using nephelometry or other techniques for measuring turbidity. The decrease in turbidity can be correlated 30 to the amount of antigen in the sample.
.:-~Z~16~
The foregoing description of the invention and the examples demonstrating the application of the invention to assays for IgE are but exemplary of the various ways the invention can be utilized. That other variations will be useful will be apparent to those skilled in the art. Therefore, the present invention is to be con-sidered limited only by the appended claims.
Claims (91)
1. In an immunometric assay process to determine the presence or concentration of an antigenic substance in a fluid sample comprising forming a ternary complex of the antigenic substance, a first antibody and a second antibody bound to the antigen at a different site than the first antibody by contacting the sample with said first and second antibodies, the improvement comprising employing a monoclonal antibody for each of said first and second antibodies.
2. A process according to claim 1 wherein a fluor-escent chromophore is bonded to said first antibody and a chromophore capable of absorbing light at the wavelength emitted by the fluorescent chromophore is bonded to said second antibody.
3. A process according to claim 2 wherein the sample is contacted with a solution containing the first and second antibodies to form the ternary complex and the intensity of fluorescence determined and compared to the fluorescence of a standard sample free of said antigen or containing said antigen in a known amount.
4. A process according to claim 2 wherein the first antibody is bound at the time of said determination to a solid carrier that is insoluble in the fluid sample and said second antibody is soluble in the fluid sample.
5. A process according to claim 4 wherein the fluid sample is simultaneously contacted with said first and second antibodies to form an insoluble ternary complex and the intensity of fluorescence of the ternary complex determined and compared to the fluorescence of a stan-dard sample free of said antigen or containing said antigen in a known amount.
6. A process according to claim 2 wherein the second antibody is bound at the time of said determination to a solid carrier that is insoluble in the fluid sample and said first antibody is soluble in the fluid sample.
7. A process according to claim 6 wherein the fluid sample is simultaneously contacted with said first and second antibodies to form an insoluble complex and the intensity of fluorescence of the fluid determined and compared to the fluorescence of a standard sample free of said antigen or containing said antigen in a known amount.
8. A process according to claim 4 wherein the sample is first contacted with the first antibody to form an antibody:antigen binary complex and then contacted with the second antibody to form the ternary complex and the intensity of the fluorescence of the complex or the fluid determined and compared to a standard sample free of said antigen or containing the antigen in a known amount.
9. A process according to claims 2, 3, or 4 wherein the fluorescent chromophore is fluorescein and the chromophore capable of absorbing emitted light is rhoda-mine.
10. A process according to claims 5, 6, or 7 wherein the fluorescent chromophore is fluorescein and the chromophore capable of absorbing emitted light is rhodamine.
11. A process according to claim 8 wherein the fluorescent chromophore is fluorescein and the chromo-phore capable of absorbing emitted light is rhodamine.
12. A process according to claim 1 wherein said first antibody is bound to particles insoluble in the fluid sample and said second antibody is bound to par-ticles insoluble in the fluid sample and wherein the sample is contacted with a suspension of the particles for a time sufficient to cause formation of the ternary complex whereby agglomeration of the particles bound to said first and second antibodies occurs.
13. A process according claim 12 wherein the size of the particles is in the range of from about 0.2µ to about 10µ.
14. A process according to claim 13 wherein the particles are selected from the group consisting of particles of latex, silica, glass, cells, polyacryl-amide, polymethyl methacrylate and agarose.
15. A process according to claim 14 wherein the particles are latex particles.
16. A process according to claim 12 wherein the particles binding the first antibody are of different color than the particles binding the second antibody.
17. A process according to claims 14 or 15 wherein the particles binding the first antibody are of different color than the particles binding the second antibody.
18. A process according to claims 13, 14, or 15 wherein the size of the particles is in the range of from about 1.0 to 10 µ.
19. A process according to claim 16 wherein the size of the particles is in the range of from about 1.0 to 10 µ.
20. A process according to claims 12 or 13 wherein the turbidity of the sample after formation of the ter-nary complex is determined and related to the turbidity of a control sample known to be free of the anitgen or to contain a known amount of the antigen.
21. A process according to claims 14 or 15 wherein the turbidity of the sample after formation of the ter-nary complex is determined and related to the turbidity of a control sample known to be free of the antigen or to contain a known amount of the antigen.
22. A process according to claim 12 wherein a fluorescent chromophore is bound to said first anti-body and a chromophore capable of absorbing light at the wave-length emitted by the fluorescent chromo-pore is bound to the second antibody and wherein, after said contacting, the intensity of fluorescence is determined and compared to the fluorescence of a stand-ard free of said antigen or containing said antigen in a known amount.
23. A process according to claim 14 wherein a fluorescent chromophore is bound to said first antibody and a chromophore capable of absorbing light at the wave-length emitted by the fluorescent chromophore is bound to the second antibody and wherein, after said contact-ing, the intensity of fluorescence is determined and compared to the fluorescence of a standard sample free of said antigen or containing said antigen in a known amount.
24. A process according to claim 22 wherein the fluorescent chromophore is fluorescein and the chromo-phore capable of absorbing emitted light is rhodamine.
25. A process according to claim 23 wherein the fluorescent chromophore is fluorescein and the chromo-phore capable of absorbing emitted light is rhodamine.
26. A process according to claim 1 wherein an enzyme is bound to the first antibody and a substance is bound to the second antibody whereby the enzyme interacts with the substance to permit detection of the antibody:
antigen:antibody complex.
antigen:antibody complex.
27. A process according to claim 26 wherein the substance bound to the second antibody is an enzyme.
28. A process according to claim 27 whereby the first antibody bound enzyme catalyzes a reaction which produces a product required by a reaction catalyzed by the second antibody bound enzyme.
29. A process according to claim 28 whereby the product of the reaction catalyzed by the first bound enzyme is consumed in the reaction catalyzed by the second bound enzyme.
30. A process according to claim 28 whereby the product of the reaction catalyzed by the first bound enzyme allosterically interacts with the second bound enzyme.
31. A process according to claim 30 whereby the product of the reaction catalyzed by the first bound enzyme allosterically activates the second bound enzyme.
32. A process according to claim 30 whereby the product of the reaction catalyzed by the first bound enzyme allosterically inhibits the second bound enzyme.
33. A process according to claim 28 wherein the reaction catalyzed by the second antibody bound enzyme produces a detectable product.
34. A process according to claim 30 wherein the reaction catalyzed by the second anitbody bound enzyme produces a detectable product.
35. A process according to claim 33 wherein the formation of the detectable product is detected by colorimetry, fluor-imetry, luminescence or spectrophometry.
36. A process according to claim 34, wherein the formation of the detectable product is detected by colorimetry, fluor-imetry, luminescence or spectrophotometry.
37. A process according to claim 28 wherein the reaction catalyzed by the second antibody bound enzyme consumes a detectable substance.
38. A process according to claims 30, 31 or 32 wherein the reaction catalyzed by the second antibody bound enzyme consumes a detectable substance.
39. A process according to claim 37 wherein the consumption of the detectable substance is detected by colorimetry, fluor-imetry, luminescence or spectrophotometry.
40. A process according to claim 26, wherein the substance on the second antibody undergoes a reaction catalyzed by the first antibody bound enzyme.
41. A process according to claim 40 wherein the reaction produces a substance detectable by colorimetry, fluorimetry, luminescence or spectrophotometry.
42 42. A process for the determination of the presence or concentration of an antigenic substance in a fluid, comprising the steps:
(a) contacting a sample of the fluid with a soluble first monoclonal antibody to the antigenic substance in order to form a soluble complex of the antibody and antigenic substance present in said sample, said first monoclonal antibody being labelled;
(b) contacting the soluble complex with a second monoclonal antibody bound at the time of said determination to a solid carrier, said solid carrier being insoluble in said fluid, in order to form an insoluble complex of said first monoclonal antibody, said antigenic substance and said second monoclonal antibody bound to said solid carrier;
(c) separating said solid carrier from the fluid sample and unreacted labelled antibody;
(d) measuring either the amount of labelled antibody associated with the solid carrier or the amount of unreacted labelled antibody; and (e) relating the amount of labelled antibody measured with the amount of labelled antibody measured for a control sample prepared in accordance with steps (a)-(d), said control sample being known to be free of said antigenic substance, to determine the presence of antigenic substance in said fluid sample, or relating the amount of labelled antibody measured with the amount
(a) contacting a sample of the fluid with a soluble first monoclonal antibody to the antigenic substance in order to form a soluble complex of the antibody and antigenic substance present in said sample, said first monoclonal antibody being labelled;
(b) contacting the soluble complex with a second monoclonal antibody bound at the time of said determination to a solid carrier, said solid carrier being insoluble in said fluid, in order to form an insoluble complex of said first monoclonal antibody, said antigenic substance and said second monoclonal antibody bound to said solid carrier;
(c) separating said solid carrier from the fluid sample and unreacted labelled antibody;
(d) measuring either the amount of labelled antibody associated with the solid carrier or the amount of unreacted labelled antibody; and (e) relating the amount of labelled antibody measured with the amount of labelled antibody measured for a control sample prepared in accordance with steps (a)-(d), said control sample being known to be free of said antigenic substance, to determine the presence of antigenic substance in said fluid sample, or relating the amount of labelled antibody measured with the amount
43 of labelled antibody measured for samples containing known amounts of antigenic substance prepared in accor-dance with steps (a)-(d) to determine the concentration of antigenic substance in said fluid sample.
43. A process according to claim 42 wherein said first monoclonal antibody is the product of a different cell line than said second monoclonal antibody.
43. A process according to claim 42 wherein said first monoclonal antibody is the product of a different cell line than said second monoclonal antibody.
44. A process according to claim 42 wherein said antigen has at least two identical binding sites and said first and second monoclonal antibodies are the product of the same cell line.
45. A process according to any one of claims 42, 43 or 44 wherein the first and second antibodies are selected to have an affinity for said antigen of at least about 108 litres/mole.
46. A process according to any one of claims 42, 43 or 44 wherein the first and second antibodies are selected to have an affinity for said antigen of at least 109 liters/mole.
47. A process according to claim 42 wherein said solid carrier is washed to separate the fluid sample from the carrier.
48. A process according to claim 47 wherein the solid carrier is washed with phosphate buffered saline.
49. A process according to claim 42 wherein the labelled antibody is labelled with a member selected from the group consisting of a radioactive isotope, an enzyme and a fluorogenic material and said examination is by means selected from the group consisting of radiometric means, fluorometric means and enzymatic means.
50. A process according to claim 49 wherein said label is the radioactive isotope I125.
51. A process for the determination of the presence of an antigenic substance in a fluid comprising the steps:
a) simultaneously contacting a sample of the fluid with first and second monoclonal antibodies to said antigenic substance, said first monoclonal antibody being labelled and said second monoclonal antibody being bound at the time of said determination to a solid carrier insoluble in said fluid, in order to form an insoluble complex of said first monoclonal antibody, said antigenic substance and said second monoclonal antibody;
b) separating said solid carrier from the fluid sample and unreacted labelled antibody;
c) measuring either the amount of labelled antibody associated with the solid carrier or the amount of unreacted labelled antibody; and d) relating the amount of labelled antibody measured with the amount of labelled antibody measured for a control sample prepared in accordance with steps (a)-(c), said control sample being known to be free of said antigenic substance, to determine the presence of antigenic substance in said fluid sample, or relating the amount of labelled antibody measured with the amount of labelled antibody measured for samples containing known amounts of antigenic substance prepared in accordance with steps (a)-(d) to determine the concentration of antigenic substance in said fluid sample.
a) simultaneously contacting a sample of the fluid with first and second monoclonal antibodies to said antigenic substance, said first monoclonal antibody being labelled and said second monoclonal antibody being bound at the time of said determination to a solid carrier insoluble in said fluid, in order to form an insoluble complex of said first monoclonal antibody, said antigenic substance and said second monoclonal antibody;
b) separating said solid carrier from the fluid sample and unreacted labelled antibody;
c) measuring either the amount of labelled antibody associated with the solid carrier or the amount of unreacted labelled antibody; and d) relating the amount of labelled antibody measured with the amount of labelled antibody measured for a control sample prepared in accordance with steps (a)-(c), said control sample being known to be free of said antigenic substance, to determine the presence of antigenic substance in said fluid sample, or relating the amount of labelled antibody measured with the amount of labelled antibody measured for samples containing known amounts of antigenic substance prepared in accordance with steps (a)-(d) to determine the concentration of antigenic substance in said fluid sample.
52. A process according to claim 51 wherein said first monoclonal antibody is the product of a different cell line than said second monoclonal antibody.
53. A process according to claim 51 wherein said antigen has at least two identical binding sites and said first and second monoclonal antibodies are the product of the same cell line.
54. A process according to any one of claims 51, 52 or 53 wherein the first and second antibodies are selected to have an affinity for said antigen of at least about 108 liters/mole.
55. A process according to any one of claims 51, 52 or 53 wherein the first and second antibodies are selected to have an affinity for said antigen of at least about 109 liters/mole.
56. A process according to claim 51 wherein said solid carrier is washed to separate the fluid sample from the carrier.
57. A process according to claim 56 wherein the solid carrier is washed with phosphate buffered saline.
58. A process according to claim 51 wherein the labelled antibody is labelled with a member selected from the group consisting of a radioactive isotope, an enzyme and a fluorogenic material and said examination is by means selected from the group consisting of radiometric means, fluorometric means and enzymatic means.
59. A process according to claim 58 wherein said label is the radioactive isotope I125.
60. In an immunometric assay for the determination of the presence or concentration of an antigenic substance in a sample of a fluid comprising forming a ternary complex to a first labelled antibody, said antigenic substance, and a second antibody, said second antibody being bound at the time of said determination to a carrier insoluble in said fluid, the improvement comprising employing a monoclonal antibody for each of said labelled antibody and said antibody bound to a solid carrier.
61. A process according to claim 60 wherein the fluid sample is first contacted with the second antibody to form a binary complex of the antigenic substance and said second antibody insoluble in the fluid and then contacted with said first labelled antibody to form the ternary complex.
62. A process according to claim 60 wherein the fluid sample is first contacted with the second antibody to form a binary complex of the antigenic substance and said second antibody insoluble in the fluid, the sample separated from the solid carrier and the solid carrier contacted with a solution of said first labelled antibody to form said ternary complex.
63. A process according to claim 60 wherein said first monoclonal antibody is the product of a different cell line than said second monoclonal antibody.
64. A process according to claim 61 wherein said first monoclonal antibody is the product of a different cell line than said second monoclonal antibody.
65. A process according to claim 62 wherein said first monoclonal antibody is the product of a different cell line than said second monoclonal antibody.
66. A process according to claim 60 wherein said antigen has at least two identical binding sites and said first and second monoclonal antibodies are the product of the same cell line.
67. A process according to claim 61 wherein said antigen has at least two identical binding sites and said first and second monoclonal antibodies are the product of the same cell line.
68. A process according to claim 62 wherein said antigen has at least two identical binding sites and said first and second monoclonal antibodies are the product of the same cell line.
69. A process according to any one of claims 60, 61, 62, 63, 64, 65, 66, 67 or 68, wherein the first and second antibodies are selected to have an affinity for said antigen of at least about 108 liters/mole.
70. A process according to any one of claims 60, 61, 62, 63, 64, 65, 66, 67 or 68 wherein the first and second antibodies are selected to have an affinity for said antigen at least about 109 liters/mole.
71. A process according to claim 62 wherein said solid carrier is washed to separate the fluid sample from the carrier.
72. A process according to claim 71 wherein the solid carrier is washed with phosphate buffered saline.
73. A process according to claim 60 wherein the labelled antibody is labelled with a member selected from the group consisting of a radioactive isotope, an enzyme and a fluorogenic material.
74. A process according to claim 73 wherein said label is the radioactive isotope I125.
75. In an immunometric assay kit for the determination of the presence or concentration of an antigenic substance in a sample of a fluid comprising reagents for forming a ternary complex to a first labelled antibody, said antigenic substance, and a second antibody, said second antibody being bound at the time of said determination to a carrier insoluble in said fluid, the improvement comprising employing a monoclonal antibody for each of said labelled antibody and said antibody bound to a solid carrier.
76. A kit according to claim 75 wherein said first monoclonal antibody is the product of a different cell line than said second monoclonal antibody.
77. A kit according to claim 75 wherein said antigen has at least two identical binding sites and said first and second monoclonal antibodies are the product of the same cell line.
78. A kit according to any one of claims 75, 76 or 77 wherein the first and second antibodies are selected to have an affinity for said antigen of at least about 108 liters/mole.
79. A kit according to any one of claims 75, 76 or 77 wherein the first and second antibodies are selected to have an affinity for said antigen of at least about 109 liters/mole.
80. A kit according to claim 75 wherein the labelled antibody is labelled with a member selected from the group consisting of a radioactive isotope, an enzyme and a fluorogenic material.
81. A kit according to claim 80 wherein said label is the radioactive isotope I125.
82. A reagent for immunological assay of antigens based on the sandwich method, characterized in that it comprises insolubilized monoclonal antibody and labelled monoclonal antibody, said monoclonal antibodies respectively being capable of distinguishing and binding to different antigen determinants of an antigen to be assayed.
83. An improved sandwich method for immunological assay of antigens wherein the improvement resides in the fact that insolubilized antibody and labelled antibody react simultaneously with an antigen to be assayed, said insolubilized antibody and labelled antibody comprising monoclonal antibodies capable of distinguishing and respectively binding to different antigen determinants of said antigen.
84. An improved sandwich method for immunological assay of antigens wherein the improvement resides in the fact that insolubilised antibody and labelled antibody react simultaneously or in several incubation steps with an antigen to be assayed, said insolubilized antibody and labelled antibody comprising monoclonal antibodies capable of distinguishing and respectively binding to different antigen determinants of said antigen.
85. A mixture of monoclonal antibodies useful in an enhanced sensitivity assay for detecting an antigen in a sample which comprises an effective assaying amount of each of at least two monoclonal antibodies which bind to different antigenic sites on the antigen and which are capable under appropriate conditions of forming a stable complex which includes the antigen and all of the monoclonal antibodies.
86. A reagent according to claim 82 wherein said monoclonal antibodies are selected to have an affinity for said antigen of at least about 108 liters/mole.
87. A reagent according to claim 82 wherein said monoclonal antibodies are selected to have an affinity for said antigen of at least about 109 liters/mole.
88. The method according to claim 83 or 84 wherein said monoclonal antibodies are selected to have an affinity for said antigen of at least about 108 liters/mole.
89. The method according to claim 83 or 84 wherein said monoclonal antibodies are selected to have an affinity for said antigen of at least about 109 liters/mole.
90. A mixture according to claim 85 wherein each of said monoclonal antibodies is selected to have an affinity for said antigen of at least about 108 liters/mole.
91. A mixture according to claim 85 wherein each of said monoclonal antibodies is selected to have an affinity for said antigen of at least about 109 liters/mole.
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Families Citing this family (1493)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5643732A (en) * | 1971-05-20 | 1997-07-01 | Strahilevitz; Meir | Immunological assay methods |
US6406920B1 (en) | 1980-06-20 | 2002-06-18 | Inverness Medical Switzerland Gmbh | Processes and apparatus for carrying out specific binding assays |
EP0111762B1 (en) * | 1980-06-20 | 1987-11-19 | Unilever Plc | Processes and apparatus for carrying out specific binding assays |
EP0044219A1 (en) * | 1980-07-16 | 1982-01-20 | Unilever Plc | Methods of immuno analysis using monoclonal antibodies |
NL185309C (en) * | 1980-07-28 | 1990-03-01 | Akzo Nv | METHOD FOR DETERMINING ANTIGENS USING TWO OR MORE MONOCLONAL ANTIBODIES AND IMMUNE REAGENTS. |
US4376110A (en) * | 1980-08-04 | 1983-03-08 | Hybritech, Incorporated | Immunometric assays using monoclonal antibodies |
US4879219A (en) * | 1980-09-19 | 1989-11-07 | General Hospital Corporation | Immunoassay utilizing monoclonal high affinity IgM antibodies |
WO1982001773A1 (en) * | 1980-11-07 | 1982-05-27 | Secher David S | Assay for interferon |
US4837167A (en) * | 1981-01-30 | 1989-06-06 | Centocor, Inc. | Immunoassay for multi-determinant antigens using high-affinity |
US4680258A (en) * | 1981-03-24 | 1987-07-14 | Sloan-Kettering Institute For Cancer Research | Process for sex determination in man by use of monoclonal antibodies to the H-Y antigen |
JPS585659A (en) * | 1981-06-24 | 1983-01-13 | ハイブリテツク インコ−ポレ−テツド | Immunological inhibition test using single clone property antigen |
US4474893A (en) * | 1981-07-01 | 1984-10-02 | The University of Texas System Cancer Center | Recombinant monoclonal antibodies |
DE3263249D1 (en) * | 1981-08-21 | 1985-05-30 | Hoffmann La Roche | Method for the determination of carcinoembryonic antigen (cea) and suitable antibody solution for the determination |
US4661586A (en) * | 1981-11-17 | 1987-04-28 | The Board Of Trustees Of The Leland Stanford Junior University | Monoclonal anti-idiotype antibodies |
EP0082636B2 (en) * | 1981-12-11 | 2006-10-18 | The Welsh National School of Medicine | Luminescent labelling materials and procedures |
USRE32011E (en) * | 1981-12-14 | 1985-10-22 | Scripps Clinic And Research Foundation | Ultrapurification of factor VIII using monoclonal antibodies |
US4444878A (en) * | 1981-12-21 | 1984-04-24 | Boston Biomedical Research Institute, Inc. | Bispecific antibody determinants |
CA1213229A (en) * | 1982-04-12 | 1986-10-28 | Gary S. David | Antibodies having dual specificities, their preparation and uses therefor |
US4483929A (en) * | 1982-05-03 | 1984-11-20 | Liposome Technology Incorporated | Liposomes with glycolipid-linked antibodies |
US4514505A (en) * | 1982-05-21 | 1985-04-30 | The Trustees Of Columbia University In The City Of New York | Monoclonal antibody mixtures and use thereof for enhanced sensitivity immunoassays |
US4792528A (en) * | 1982-05-21 | 1988-12-20 | The Trustees Of Columbia University In The City Of New York | Methods for obtaining monoclonal antibodies useful in enhanced sensitivity immunoassays |
US4443427A (en) * | 1982-06-21 | 1984-04-17 | Sidney Farber Cancer Institute, Inc. | Monoclonal antibody |
US4623621A (en) * | 1982-06-24 | 1986-11-18 | Hoffmann-La Roche Inc. | Immunoassay for peptide and protein oligomers |
DE3225027A1 (en) * | 1982-07-05 | 1984-01-05 | Boehringer Mannheim Gmbh, 6800 Mannheim | IMMUNCHEMICAL MEASUREMENT METHOD |
US4471058A (en) * | 1982-07-26 | 1984-09-11 | Board Of Trustees Operating Michigan State University | Method for the detection and/or determination of a polyvalent antigen using at least two different monoclonal antibodies |
US4879218A (en) * | 1982-09-13 | 1989-11-07 | Virginia Tech Intellectual Properties, Inc. | Antibody for C.difficile |
JPS5954966A (en) * | 1982-09-22 | 1984-03-29 | Mochida Pharmaceut Co Ltd | Immunological measuring reagent |
US4596771A (en) * | 1982-09-27 | 1986-06-24 | Research Corporation | Monoclonal antibodies to vitamin B-6 and immunossay method |
US4659678A (en) * | 1982-09-29 | 1987-04-21 | Serono Diagnostics Limited | Immunoassay of antigens |
US4844966A (en) * | 1982-10-13 | 1989-07-04 | Minnesota Mining And Manufacturing Company | Assaying total IgE levels with fluorogenic enzyme labeled antibody |
US4845027B1 (en) * | 1982-10-13 | 1994-05-10 | Biowhittaker Inc | Fluorometric assay of allergic reactions |
US4539292A (en) * | 1982-12-29 | 1985-09-03 | Reid Michael J | Immunoassay technique for specific immunoglobulin E |
DE3485733D1 (en) * | 1983-01-21 | 1992-06-25 | Frederick James Primus | SPECIFIC ANTIGENS OF THE CEA (KARZYNO-EMBRYONALES-ANTIGEN) FAMILY, SPECIFIC ANTIBODIES AND METHOD FOR THEIR USE. |
US4818709A (en) * | 1983-01-21 | 1989-04-04 | Primus Frederick J | CEA-family antigens, Anti-CEA antibodies and CEA immunoassay |
US4525452A (en) * | 1983-01-24 | 1985-06-25 | Btc Diagnostics Limited Partnership | Enzyme immunoassay with step of immersing sample in deionized water |
US4994373A (en) | 1983-01-27 | 1991-02-19 | Enzo Biochem, Inc. | Method and structures employing chemically-labelled polynucleotide probes |
US4849337A (en) * | 1983-01-31 | 1989-07-18 | Minnesota Mining And Manufacturing Company | Assaying allergen specific IgE levels with fluorogenic enzyme labeled antibody |
US4558006A (en) * | 1983-02-04 | 1985-12-10 | Kirin-Amgen, Inc. | A.T.C.C. HB8209 and its monoclonal antibody to erythropoietin |
US5106760A (en) * | 1983-02-04 | 1992-04-21 | Kirin-Amgen | ATCC HB8209, its monoclonal antibody to erythropoietin and assay using same |
US4474892A (en) * | 1983-02-16 | 1984-10-02 | Board Of Trustees Of The Leland Stanford Junior University | Two-site immunoassays using monoclonal antibodies of different classes or subclasses and test kits for performing same |
FR2541304A1 (en) * | 1983-02-21 | 1984-08-24 | Centre Nat Rech Scient | ANTI-LEGIONELLA MONOCLONAL ANTIBODIES, METHOD OF OBTAINING AND PNEUMONIA DIAGNOSTIC APPLICATION |
US5084379A (en) * | 1983-04-29 | 1992-01-28 | Biowhittaker, Inc. | Fluorometric assay of chymopapain hypersensitivity and reagents therefor |
WO1984004598A1 (en) * | 1983-05-06 | 1984-11-22 | Univ Columbia | Immunoassay for human chorionic gonadotropin |
US4851356A (en) * | 1983-05-06 | 1989-07-25 | The Trustees Of Columbia University In The City Of New York | Immunoassay for human chorionic gonadotropin |
US4642284A (en) * | 1983-06-13 | 1987-02-10 | Scripps Clinic And Research Foundation | Method and system for detection of complement pathway activation |
GB8317124D0 (en) * | 1983-06-23 | 1983-07-27 | Ekins R P | Free ligand assay |
USRE34405E (en) * | 1983-08-01 | 1993-10-12 | Abbott Laboratories | Determination of analytes in particle-containing medium |
WO1985000750A1 (en) * | 1983-08-18 | 1985-02-28 | Quidel | Hybridoma cell line producing suppressive factor of allergy |
US4828981A (en) * | 1983-08-24 | 1989-05-09 | Synbiotics Corporation | Immunoassays for determining Dirofilaria immitis infection using antiidiotype monoclonal antibody reagents |
JPS6060557A (en) * | 1983-09-13 | 1985-04-08 | Eisai Co Ltd | Method and reagent for measuring pivka-ii |
JPS6080768A (en) * | 1983-10-12 | 1985-05-08 | Eisai Co Ltd | Method and reagent for measuring basic fetal protein |
US4595661A (en) * | 1983-11-18 | 1986-06-17 | Beckman Instruments, Inc. | Immunoassays and kits for use therein which include low affinity antibodies for reducing the hook effect |
US6057121A (en) * | 1983-11-29 | 2000-05-02 | Igen International, Inc. | Method of catalyzing stereochemical reactions |
US5229272A (en) * | 1989-04-25 | 1993-07-20 | Igen, Inc. | Catalytic antibody components |
US6846654B1 (en) | 1983-11-29 | 2005-01-25 | Igen International, Inc. | Catalytic antibodies as chemical sensors |
US4839275A (en) * | 1983-12-01 | 1989-06-13 | The Jewish Hospital | Circulating antigens of dirofilaria immitis, monoclonal antibodies specific therefor and methods of preparing such antibodies and detecting such antigens |
WO1985002685A1 (en) * | 1983-12-12 | 1985-06-20 | Meru, Inc. | Method and materials for the identification of lipopolysaccharide producing microorganisms |
US4683196A (en) * | 1983-12-12 | 1987-07-28 | Meru, Inc. | Method and materials for the identification of lipopolysaccharide producing microorganisms |
US4610960A (en) * | 1983-12-21 | 1986-09-09 | Wisconsin Alumni Research Foundation | Monoclonal antibody to thrombospondin and method for assaying for and isolating thrombospondin |
US4666865A (en) * | 1984-01-13 | 1987-05-19 | Centocor, Inc. | Immunoassay for biologically active human interferon-gamma employing unique monoclonal antibodies |
US4757001A (en) * | 1984-02-16 | 1988-07-12 | Fujirebio Kabushiki Kaisha | Method of measuring biological ligand by utilizing amylase |
GB8404368D0 (en) * | 1984-02-20 | 1984-03-28 | Cogent Ltd | Monoclonal antibodies to human cytomegalovirus |
US4865997A (en) * | 1984-02-23 | 1989-09-12 | Becton Dickinson And Company | Assay for ligands by separating bound and free tracer from sample |
US4690890A (en) * | 1984-04-04 | 1987-09-01 | Cetus Corporation | Process for simultaneously detecting multiple antigens using dual sandwich immunometric assay |
US4780401A (en) * | 1984-04-09 | 1988-10-25 | Ciba-Geigy Corporation | Novel monoclonal antibodies to human renin and hybridoma cells, processes for their preparation and their applications |
US5011771A (en) * | 1984-04-12 | 1991-04-30 | The General Hospital Corporation | Multiepitopic immunometric assay |
GR850899B (en) * | 1984-04-12 | 1985-11-25 | Gen Hospital Corp | |
CA1260372A (en) * | 1984-04-27 | 1989-09-26 | Elazar Rabbani | Hybridization method for the detection of genetic materials |
US4632901A (en) * | 1984-05-11 | 1986-12-30 | Hybritech Incorporated | Method and apparatus for immunoassays |
ZA853756B (en) * | 1984-06-01 | 1986-01-29 | Miles Lab | Nucleic acid hybridization assay employing immobilized rna probes |
US4731326A (en) * | 1984-06-04 | 1988-03-15 | Ortho Diagnostic Systems Inc. | Disease diagnosis by detection of shed normal tissue antigens |
US4636478A (en) * | 1984-07-16 | 1987-01-13 | Becton, Dickinson And Company | Monoclonal antibodies recognizing L-thyroxine |
WO1986000993A1 (en) * | 1984-08-01 | 1986-02-13 | Advanced Biotechnology Associates, Inc. | A salmonella-specific analyses reagent |
US4707438A (en) * | 1984-08-22 | 1987-11-17 | Tel Aviv University | Immunoassay for breast cancer employing monoclonal antibodies |
AU4777185A (en) * | 1984-08-28 | 1986-03-24 | Hybritech Inc. | Article for diagnostic assays |
US4745075A (en) * | 1984-09-06 | 1988-05-17 | Burroughs Wellcome Co. | Diagnostic test methods |
EP0198826A4 (en) * | 1984-10-29 | 1989-03-23 | Eks Inc | Immunoassay method for small molecules. |
DE3587835T2 (en) * | 1984-10-31 | 1994-10-20 | Alcon Lab Inc | SANDWICH IMMUNOTEST PROCEDURE FOR ANTIGENS IN OPHTHALMIC DISORDERS. |
US4713347A (en) * | 1985-01-14 | 1987-12-15 | Sensor Diagnostics, Inc. | Measurement of ligand/anti-ligand interactions using bulk conductance |
JPH0672893B2 (en) * | 1985-08-16 | 1994-09-14 | 富士薬品工業株式会社 | Determination of human prolyl hydroxylase in human blood by radioimmunoassay. |
DE3508384A1 (en) * | 1985-03-08 | 1986-11-06 | Boehringer Mannheim Gmbh, 6800 Mannheim | INHIBITION OF HUMAN SALIVARY AND PANCREASAMYLASE BY MONOCLONAL ANTIBODIES |
DE3509958A1 (en) * | 1985-03-20 | 1986-09-25 | Bayer Ag, 5090 Leverkusen | MONOCLONAL ANTIBODIES AGAINST ATRIALE, NATRIURETIC PEPTIDES OF HUMANS |
US4722889A (en) * | 1985-04-02 | 1988-02-02 | Leeco Diagnostics, Inc. | Immunoassays using multiple monoclonal antibodies and scavenger antibodies |
US4707443A (en) * | 1985-04-19 | 1987-11-17 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Soluble interleukin-2 receptor as a disease indicator and a method of assaying the same |
US4935339A (en) * | 1985-05-07 | 1990-06-19 | Nichols Institute Diagnostics | Delayed solid phase immunologic assay |
US4737456A (en) * | 1985-05-09 | 1988-04-12 | Syntex (U.S.A.) Inc. | Reducing interference in ligand-receptor binding assays |
US5273882A (en) * | 1985-06-13 | 1993-12-28 | Amgen | Method and kit for performing nucleic acid hybridization assays |
US4931385A (en) * | 1985-06-24 | 1990-06-05 | Hygeia Sciences, Incorporated | Enzyme immunoassays and immunologic reagents |
US5112738A (en) * | 1985-07-03 | 1992-05-12 | Miles Inc. | Histamine derivatives, immunogen conjugates and antibodies raised thereto |
US4910133A (en) * | 1985-08-29 | 1990-03-20 | Ube Industries, Limited | Diagnostic test drug comprising monoclonal antibody to human copper.zinc-superoxide dismutase and diagnostic test method using the same |
US5063151A (en) * | 1985-09-20 | 1991-11-05 | Biometallics, Inc. | Immunoassay method and kit |
US5595908A (en) * | 1985-09-26 | 1997-01-21 | University Of Southern Mississipi | Piezoelectric device for detection of polynucleotide hybridization |
US4933275A (en) * | 1985-10-24 | 1990-06-12 | The General Hospital Corporation | Method for the detection of a polypeptide subunit in the presence of a quaternary protein containing the subunit |
US6265176B1 (en) | 1985-10-29 | 2001-07-24 | Cordis Corporation | Dot immunoassay on plastic sheets |
US4770993A (en) * | 1985-10-31 | 1988-09-13 | Beatrice Companies, Inc. | Hybridoma tumor cell lines and their monoclonal antibodies to thaumatin |
US5501949A (en) * | 1985-12-10 | 1996-03-26 | Murex Diagnostics Corporation | Particle bound binding component immunoassay |
US4868108A (en) * | 1985-12-12 | 1989-09-19 | Hygeia Sciences, Incorporated | Multiple-antibody detection of antigen |
US4810639A (en) * | 1985-12-20 | 1989-03-07 | E. I. Du Pont De Nemours And Company | Immunoassay for CK-MB using bound and soluble antibodies |
US4772551A (en) * | 1985-12-26 | 1988-09-20 | Neogen Corporation | Method and test kit for detecting a trichothecene using novel monoclonal antibodies |
US5175113A (en) * | 1986-01-16 | 1992-12-29 | Novo Nordisk A/S | Modified β2 -microglobulin |
US4741999A (en) * | 1986-02-26 | 1988-05-03 | The Research Foundation Of State University Of New York | Monoclonal antibodies useful in the identification of microorganisms causing periodontal disease |
JPS62231168A (en) | 1986-03-21 | 1987-10-09 | ハイブリテツク・インコ−ポレイテツド | Improvement method for forming internal standard for analyzing analite-receptor |
AU7202887A (en) * | 1986-03-26 | 1987-10-20 | Murex Corp. | Device and method for determining microbial resistance to antimicrobic agents |
US5292636A (en) * | 1986-03-31 | 1994-03-08 | T Cell Diagnostics, Inc. | Therapeutic and diagnostic methods using soluble T cell surface molecules |
US5426029A (en) * | 1986-03-31 | 1995-06-20 | T Cell Diagnostics, Inc. | Therapeutic and diagnostic methods using leukocyte surface antigens |
US5006459A (en) * | 1986-03-31 | 1991-04-09 | T Cell Sciences, Inc. | Therapeutic and diagnostic methods using soluble T cell surface molecules |
US6881536B1 (en) * | 1986-04-30 | 2005-04-19 | Bioveris Corporation | Particle based electrochemiluminescent assays |
US4963355A (en) * | 1986-06-23 | 1990-10-16 | Igen, Inc. | Production of antibody catalysts |
US5120504A (en) * | 1986-07-14 | 1992-06-09 | Hybritech Incorporated | Apparatus for immunoassays with vent chennels in the container side wall |
ES2070820T3 (en) * | 1986-08-06 | 1995-06-16 | Scripps Clinic Res | MONOCLONAL ANTIBODIES SPECIFIC TO APOLIPOPROTEIN B, PRODUCED BY TWO NEW HYBRIDOMES. |
US4935343A (en) * | 1986-08-08 | 1990-06-19 | Syntex (U.S.A.) Inc. | Monoclonal antibodies for interleukin-1β |
US5316914A (en) * | 1986-09-04 | 1994-05-31 | Fuji Yakuhin Kogyo Kabushiki Kaisha | Method for determining human collagen peptides by way of enzyme immunoassay |
JP2617299B2 (en) * | 1986-09-17 | 1997-06-04 | ダイナボット 株式会社 | Immunoassay method for elastase 1 |
US5763262A (en) * | 1986-09-18 | 1998-06-09 | Quidel Corporation | Immunodiagnostic device |
US20010023075A1 (en) * | 1992-04-03 | 2001-09-20 | Siu-Yin Wong | A immunodiagnositc device having a dessicant incorporated therein |
US4828986A (en) * | 1986-09-29 | 1989-05-09 | Scripps Clinic And Research Foundation | Assay method and diagnostic system for determining the ratio of APO B-100 to APO A-I in a blood sample |
US4804626A (en) * | 1986-10-22 | 1989-02-14 | The General Hospital Corporation | Immunometric assay for the detection of human chorionic gonadotropin |
US4911909A (en) * | 1987-01-02 | 1990-03-27 | E. I. Du Pont De Nemours And Company | Method of controlling hypertension using monoclonal antibodies to angiotensin-II |
US4940659A (en) * | 1987-02-20 | 1990-07-10 | Monoclonetics International, Inc. | Screening extra-cellular body fluids for superoxide dismutase (SOD-1) for determining fetal trisomy 21 down syndrome |
US5789235A (en) * | 1987-03-23 | 1998-08-04 | Tackett; Scott E. | Modifying cell metabolism via extra-cellular nucleases |
DE3714147A1 (en) * | 1987-04-28 | 1988-11-17 | Boehringer Mannheim Gmbh | IMMUNCHEMICAL METHOD AND REAGENT FOR DETERMINING A POLYVALENT ANTIGENT IN A LIQUID SAMPLE |
US4788138A (en) * | 1987-04-30 | 1988-11-29 | Beckman Instruments, Inc. | Method to achieve a linear standard curve in a sandwich immunoassay |
US5474899A (en) * | 1987-05-13 | 1995-12-12 | Cistron Biotechnology, Inc. | Selective immunoassay for IL-1 β |
US5149626A (en) * | 1987-05-14 | 1992-09-22 | Mclean Hospital Corporation | Multiple antigen immunoassay |
FR2615622B1 (en) * | 1987-05-19 | 1994-05-06 | Ire Medgenix Sa | PLASMATIC ASSAY OF MONOKINES |
US4971904A (en) * | 1987-06-26 | 1990-11-20 | E. I. Du Pont De Nemours And Company | Heterogeneous immunoassay |
US5009998A (en) * | 1987-06-26 | 1991-04-23 | E. I. Du Pont De Nemours And Company | Method for performing heterogeneous immunoassay |
US5179000A (en) * | 1987-07-24 | 1993-01-12 | Nippon Kayaku Kabushiki Kaisha | Method for assaying basic fetoprotein in urine and assay kit therefor |
US5447837A (en) * | 1987-08-05 | 1995-09-05 | Calypte, Inc. | Multi-immunoassay diagnostic system for antigens or antibodies or both |
WO1989001784A1 (en) * | 1987-09-02 | 1989-03-09 | Kim Peter S | Production of immunoproximity catalysts |
US6461825B1 (en) * | 1987-09-30 | 2002-10-08 | Sanofi (Societe Anonyme) | Immunometric assay kit and method applicable to whole cells |
US4859612A (en) * | 1987-10-07 | 1989-08-22 | Hygeia Sciences, Inc. | Metal sol capture immunoassay procedure, kit for use therewith and captured metal containing composite |
DE3734015A1 (en) * | 1987-10-08 | 1989-04-20 | Behringwerke Ag | DIAGNOSTIC AGENT AND METHOD FOR DETERMINING APOLIPOPROTEIN B |
US5231000A (en) * | 1987-10-08 | 1993-07-27 | The Mclean Hospital | Antibodies to A4 amyloid peptide |
US5300425A (en) * | 1987-10-13 | 1994-04-05 | Terrapin Technologies, Inc. | Method to produce immunodiagnostic reagents |
US5217869A (en) * | 1987-10-13 | 1993-06-08 | Terrapin Technologies, Inc. | Method to produce immunodiagnostic reagents |
US5256372A (en) * | 1987-11-06 | 1993-10-26 | Idexx Corporation | Dipstick test device including a removable filter assembly |
US5094941A (en) * | 1987-12-31 | 1992-03-10 | Zymogenetics, Inc. | Monoclonal antibodies to PDGF |
US4891313A (en) * | 1988-01-21 | 1990-01-02 | Boehringer Manheim Corporation | Method for determination of a component of a sample |
AU3342689A (en) * | 1988-03-24 | 1989-10-16 | Igen Incorporated | Luminescent chimeric proteins |
US5202267A (en) * | 1988-04-04 | 1993-04-13 | Hygeia Sciences, Inc. | Sol capture immunoassay kit and procedure |
US6702705B1 (en) | 1988-05-04 | 2004-03-09 | Igen International, Inc. | Prodrugs activated by targeted catalytic proteins |
US5620845A (en) * | 1988-06-06 | 1997-04-15 | Ampcor, Inc. | Immunoassay diagnostic kit |
US5173399A (en) * | 1988-06-10 | 1992-12-22 | Abbott Laboratories | Mouse monoclonal antibodies to hiv-1p24 and their use in diagnostic tests |
AU2684488A (en) * | 1988-06-27 | 1990-01-04 | Carter-Wallace, Inc. | Test device and method for colored particle immunoassay |
CA1335880C (en) * | 1988-07-14 | 1995-06-13 | Thomas P. O'connor | Detection of an antibody and antigen in an immunoassay |
US5096809A (en) * | 1988-07-25 | 1992-03-17 | Pacific Biotech, Inc. | Whole blood assays using porous membrane support devices |
US5059522A (en) * | 1988-08-18 | 1991-10-22 | Wayne Lawrence G | Intrinsic enzyme dot blot immunoassay or indentification of microorganisms |
US5030555A (en) * | 1988-09-12 | 1991-07-09 | University Of Florida | Membrane-strip reagent serodiagnostic apparatus and method |
DE3836348A1 (en) * | 1988-10-25 | 1990-04-26 | Boehringer Mannheim Gmbh | METHOD FOR DETERMINING AN ANTIQUE CLASS-SPECIFIC ANTIBODY AND REAGENT SUITABLE FOR IT |
EP0368674A3 (en) * | 1988-11-11 | 1991-10-09 | SANYO CHEMICAL INDUSTRIES, Ltd. | Immunoassay and test kits therefor |
US6306594B1 (en) | 1988-11-14 | 2001-10-23 | I-Stat Corporation | Methods for microdispensing patterened layers |
US5200051A (en) * | 1988-11-14 | 1993-04-06 | I-Stat Corporation | Wholly microfabricated biosensors and process for the manufacture and use thereof |
US5322838A (en) * | 1988-11-16 | 1994-06-21 | Brigham & Women's Hospital | Use of INHIB (the C3 β-chain) in the detection and inhibition of inflammation |
US5512657A (en) * | 1988-12-12 | 1996-04-30 | Bainbridge Sciences, Inc. | Detection of complexes which include basement membrane components as diagnostic of cancer and other diseases |
US5264370A (en) * | 1988-12-12 | 1993-11-23 | Bainbridge Laboratories, Inc. | Detection of basement membrane components as diagnostic of cancer and other diseases |
CA2008304C (en) * | 1989-01-31 | 2001-03-27 | Craig S. Hill | Assay for bone alkaline phosphatase |
EP0456727A4 (en) * | 1989-02-03 | 1992-01-15 | Commonwealth Scientific And Industrial Research Organization | Monoclonal antibodies directed against vitronectin and fibronectin, and uses thereof |
US5106761A (en) * | 1989-03-13 | 1992-04-21 | International Canine Genetics, Inc. | Method for detecting molecules in a liquid medium |
US5658753A (en) * | 1989-04-25 | 1997-08-19 | Paul; Sudhir | Catalytic antibody components |
US5236836A (en) * | 1989-04-25 | 1993-08-17 | Igen, Inc. | Autoantibodies which enhance the rate of a chemical reaction |
US5599538A (en) * | 1989-04-25 | 1997-02-04 | Igen, Inc. | Autoantibodies which enhance the rate of a chemical reaction |
US6048717A (en) * | 1989-04-25 | 2000-04-11 | Igen International, Inc. | Inhibitors of catalytic antibodies |
US5318897A (en) * | 1989-04-25 | 1994-06-07 | Igen, Inc. | Monoclonal antibody and antibody components elicited to a polypeptide antigen ground state |
US5194585A (en) * | 1989-04-25 | 1993-03-16 | Igen, Inc. | Inhibitors of catalytic antibodies |
US6258360B1 (en) | 1989-05-04 | 2001-07-10 | Igen International, Inc. | Prodrugs activated by targeted catalytic proteins |
WO1990015153A1 (en) * | 1989-06-02 | 1990-12-13 | Georgetown University | A method for the detection of anti-streptokinase antibodies |
WO1990015327A1 (en) * | 1989-06-06 | 1990-12-13 | Martin Gould | Immunoassay diagnostic kit |
US5187068A (en) * | 1989-06-09 | 1993-02-16 | Nicolae Luca | Method for determination of lipid moiety and apolipoprotein expressed epitope immunoreactivity on intact lipoprotein |
US5484735A (en) * | 1989-08-23 | 1996-01-16 | Northwestern University | Immunoassay of glycosylated proteins employing antibody directed to reductively glycosylated N-terminal amino acids |
US6008057A (en) * | 1989-08-25 | 1999-12-28 | Roche Diagnostics Corporation | Immunoassay system |
US5196311A (en) * | 1989-10-27 | 1993-03-23 | Health Research, Incorporated | Elisa test for von willebrand factor |
US5202264A (en) * | 1989-10-27 | 1993-04-13 | Health Research, Incorporated | ELISA using multi-species antibodies for detection of von Willebrand factor in multiple species |
US5830709A (en) * | 1989-10-27 | 1998-11-03 | Benson; Roger E. | Detection method for homologous portions of a class of substances |
DE69033295T2 (en) * | 1989-11-03 | 2000-05-25 | Donald L Morton | Detection method for urinary carcinoma-associated antigens |
US6407061B1 (en) | 1989-12-05 | 2002-06-18 | Chiron Corporation | Method for administering insulin-like growth factor to the brain |
US5624898A (en) | 1989-12-05 | 1997-04-29 | Ramsey Foundation | Method for administering neurologic agents to the brain |
US5196324A (en) * | 1989-12-15 | 1993-03-23 | Eli Lilly And Company | Monoclonal antibodies reactive with a human atheroma associated antigen |
KR910014706A (en) * | 1990-01-10 | 1991-08-31 | 원본미기재 | Improved Immunoassay Device Without Cleaning |
AU639311B2 (en) * | 1990-01-26 | 1993-07-22 | Washington Research Foundation | Immune reactivity to expressed activated oncogenes for diagnosis and treatment of malignancy |
US6190885B1 (en) | 1990-02-02 | 2001-02-20 | Cancer Research Fund Of Contra Costa | Fusion protein containing HMFG Epitop E (S) |
US5532135A (en) * | 1990-02-02 | 1996-07-02 | Cancer Research Fund Of Contra Costa | Solid-phase competitive assay utilizing a fusion protein |
EP0468056A4 (en) * | 1990-02-07 | 1992-07-08 | Kanebo Ltd. | Anti-procollagenase monoclonal antibodies and a method for the assay of procollagenase utilizing thereof |
US5096837A (en) * | 1990-02-08 | 1992-03-17 | Pacific Biotech, Inc. | Immunochromatographic assay and method of using same |
US5922615A (en) | 1990-03-12 | 1999-07-13 | Biosite Diagnostics Incorporated | Assay devices comprising a porous capture membrane in fluid-withdrawing contact with a nonabsorbent capillary network |
US5223220A (en) * | 1990-03-27 | 1993-06-29 | Pacific Biotech, Inc. | Solid phase immunoassay device and method of making same |
DK0553113T3 (en) * | 1990-08-02 | 1999-08-09 | Antex Biolog Inc | Adhesion receptors for pathogenic or opportunistic microorganisms |
WO1992005282A1 (en) * | 1990-09-14 | 1992-04-02 | Biosite Diagnostics, Inc. | Antibodies to complexes of ligand receptors and ligands and their utility in ligand-receptor assays |
JPH085920B2 (en) * | 1991-01-21 | 1996-01-24 | 富士薬品工業株式会社 | Anti-human stromlysin monoclonal antibody and enzyme immunoassay |
US5997878A (en) | 1991-03-07 | 1999-12-07 | Connaught Laboratories | Recombinant poxvirus-cytomegalovirus, compositions and uses |
CA2055695C (en) * | 1991-04-12 | 2004-04-13 | Thomas Hyatt Duffy | Ca 195-like immunoreactive antigen from human amniotic fluid |
US5223396A (en) * | 1991-05-03 | 1993-06-29 | Boehringer Ingelheim Pharmaceuticals, Inc. | Method for detecting organ transplant rejection |
WO1992020820A1 (en) * | 1991-05-15 | 1992-11-26 | Vanderbilt University | Method to determine metastatic potential of tumor cells |
US5877028A (en) | 1991-05-29 | 1999-03-02 | Smithkline Diagnostics, Inc. | Immunochromatographic assay device |
US5869345A (en) * | 1991-05-29 | 1999-02-09 | Smithkline Diagnostics, Inc. | Opposable-element assay device employing conductive barrier |
US6168956B1 (en) | 1991-05-29 | 2001-01-02 | Beckman Coulter, Inc. | Multiple component chromatographic assay device |
US5607863A (en) * | 1991-05-29 | 1997-03-04 | Smithkline Diagnostics, Inc. | Barrier-controlled assay device |
US5998220A (en) | 1991-05-29 | 1999-12-07 | Beckman Coulter, Inc. | Opposable-element assay devices, kits, and methods employing them |
US5468648A (en) * | 1991-05-29 | 1995-11-21 | Smithkline Diagnostics, Inc. | Interrupted-flow assay device |
WO1992022668A1 (en) * | 1991-06-14 | 1992-12-23 | Vanderbilt University | Method and compositions to assess oxidative stress in vivo |
US5338660A (en) * | 1991-07-12 | 1994-08-16 | Board Of Supervisors Of Louisiana State University And Agricutural And Mechanical College | Diagnosis of Fasciola infections by detection of antigens in feces or intestinal content |
JP3183666B2 (en) * | 1991-07-19 | 2001-07-09 | アツセイ・リサーチ・インコーポレーテツド | Method and kit for measuring endogenous cytokines |
US5965379A (en) * | 1991-07-19 | 1999-10-12 | Cytimmune Sciences Inc. | Method for measuring endogenous cytokines |
US5726010A (en) * | 1991-07-31 | 1998-03-10 | Idexx Laboratories, Inc. | Reversible flow chromatographic binding assay |
US6007999A (en) * | 1991-07-31 | 1999-12-28 | Idexx Laboratories, Inc. | Reversible flow chromatographic binding assay |
US5369006A (en) * | 1991-08-20 | 1994-11-29 | E. I. Du Pont De Nemours And Company | Determination of CK isoenzymes and CK isoforms |
AU2555792A (en) | 1991-08-28 | 1993-04-05 | Nichols Institute Diagnostics | Disease associated human autoantibodies specific for human thyroid peroxidase |
DE4134297A1 (en) * | 1991-10-17 | 1993-04-22 | Behringwerke Ag | Monoclonal antibody specific for Mycoplasma pneumoniae |
EP0962529A1 (en) * | 1991-10-23 | 1999-12-08 | Thomas Jefferson University | Synthesis of human procollagens and collagens in recombinant DNA systems |
WO1993008473A1 (en) * | 1991-10-24 | 1993-04-29 | Beth Israel Hospital Association | Assay for malignant effusions |
US5525461A (en) * | 1991-11-01 | 1996-06-11 | T Cell Diagnostics, Inc. | Therapeutic and diagnostic methods using total leukocyte surface antigens |
EP0623214A1 (en) * | 1992-01-17 | 1994-11-09 | Selective Antibodies Limited | Determination of haptens |
DE69302719T2 (en) * | 1992-02-17 | 1996-09-19 | Akzo Nv | Calibrator and use of it in an immunoassay |
US5851787A (en) * | 1992-04-20 | 1998-12-22 | The General Hospital Corporation | Nucleic acid encoding amyloid precursor-like protein and uses thereof |
US5708141A (en) * | 1992-05-11 | 1998-01-13 | Corvas International, Inc. | Neutrophil inhibitors |
DE4218257A1 (en) * | 1992-06-03 | 1993-12-09 | Behringwerke Ag | Method for immunochemical determination of an analyte |
US5688936A (en) * | 1992-06-11 | 1997-11-18 | The Regents Of The University Of California | Vesicle membrane transport proteins |
US5395754A (en) * | 1992-07-31 | 1995-03-07 | Hybritech Incorporated | Membrane-based immunoassay method |
US5447838A (en) * | 1992-08-05 | 1995-09-05 | Hybritech Incorporated | Protein-dye conjugate for confirmation of correct dilution of calibrators |
US5789183A (en) * | 1992-08-14 | 1998-08-04 | University Of Arkansas | Serological detection and identification of rice blast |
US5354692A (en) * | 1992-09-08 | 1994-10-11 | Pacific Biotech, Inc. | Analyte detection device including a hydrophobic barrier for improved fluid flow |
EP0674661B1 (en) * | 1992-12-18 | 2003-07-02 | Molecular Rx., Inc. | Assay and treatment for demyelinating diseases such as multiple sclerosis |
DE606516T1 (en) * | 1993-01-13 | 1995-03-16 | Idemitsu Kosan Co | Against human ceruloplasmin monoclonal antibody. |
US5914241A (en) * | 1993-01-19 | 1999-06-22 | Biosite Diagnostics, Inc. | Assays and kits for detecting analytes in the presence of cross-reacting substances |
FR2700855B1 (en) * | 1993-01-28 | 1995-03-03 | Commissariat Energie Atomique | Immunometric determination of an antigen or a hapten. |
US7713528B1 (en) | 1993-02-18 | 2010-05-11 | Enzo Therapeutics, Inc. | Method for in vivo delivery of active compounds using reagent conjugate |
US5374531A (en) * | 1993-03-22 | 1994-12-20 | Zynaxis, Inc. | Immunoassay for determination of cells |
DE4314254A1 (en) * | 1993-04-30 | 1994-11-03 | Boehringer Mannheim Gmbh | Monoclonal antibodies to CK-MB |
WO1994029722A1 (en) * | 1993-06-08 | 1994-12-22 | Chronomed, Inc. | Two-phase optical assay method and apparatus |
SG63596A1 (en) * | 1993-07-29 | 1999-03-30 | Cor Therapeutics Inc | Receptor function assays |
US5837546A (en) * | 1993-08-24 | 1998-11-17 | Metrika, Inc. | Electronic assay device and method |
WO1995008336A1 (en) * | 1993-09-22 | 1995-03-30 | Nichols Institute Diagnostics | Graves' ophthalmopathy associated antibodies, graves' ophthalmopathy orbital antigen, and methods of use thereof |
JP3356556B2 (en) * | 1993-10-22 | 2002-12-16 | 第一化学薬品株式会社 | Method for measuring denatured lipoproteins |
US7312052B1 (en) | 1993-12-08 | 2007-12-25 | Stratagene California | Polymerase compositions and uses thereof |
US5695928A (en) * | 1993-12-10 | 1997-12-09 | Novartis Corporation | Rapid immunoassay for detection of antibodies or antigens incorporating simultaneous sample extraction and immunogenic reaction |
US6045797A (en) * | 1994-03-14 | 2000-04-04 | New York University Medical Center | Treatment or diagnosis of diseases or conditions associated with a BLM domain |
US5877016A (en) | 1994-03-18 | 1999-03-02 | Genentech, Inc. | Human trk receptors and neurotrophic factor inhibitors |
US6040137A (en) * | 1995-04-27 | 2000-03-21 | Tripep Ab | Antigen/antibody specification exchanger |
US6417324B1 (en) * | 2000-04-21 | 2002-07-09 | Tripep Ab | Synthetic peptides that bind to the hepatitis B virus core and e antigens |
US6933366B2 (en) * | 1996-12-27 | 2005-08-23 | Tripep Ab | Specificity exchangers that redirect antibodies to bacterial adhesion receptors |
US6660842B1 (en) * | 1994-04-28 | 2003-12-09 | Tripep Ab | Ligand/receptor specificity exchangers that redirect antibodies to receptors on a pathogen |
US6140099A (en) * | 1994-05-20 | 2000-10-31 | The Trustees Of The University Of Pennsylvania | Method of delaying fetal membrane rupture by inhibiting matrix metalloproteinase-9 activity |
US5708142A (en) | 1994-05-27 | 1998-01-13 | Genentech, Inc. | Tumor necrosis factor receptor-associated factors |
US6107045A (en) * | 1994-06-30 | 2000-08-22 | Oklahoma Medical Research Foundation | Antibodies to lipoproteins and apolipoproteins and methods of use thereof |
ATE201445T1 (en) | 1994-08-12 | 2001-06-15 | Myriad Genetics Inc | MUTATIONS OF THE OVARIAL AND BREAST CANCER SENSITIVITY GENE LINKED TO 17Q |
AU691958B2 (en) | 1994-08-12 | 1998-05-28 | Myriad Genetics, Inc. | 17q-linked breast and ovarian cancer susceptibility gene |
US5556752A (en) * | 1994-10-24 | 1996-09-17 | Affymetrix, Inc. | Surface-bound, unimolecular, double-stranded DNA |
US6974666B1 (en) | 1994-10-21 | 2005-12-13 | Appymetric, Inc. | Methods of enzymatic discrimination enhancement and surface-bound double-stranded DNA |
US8236493B2 (en) * | 1994-10-21 | 2012-08-07 | Affymetrix, Inc. | Methods of enzymatic discrimination enhancement and surface-bound double-stranded DNA |
JP2729159B2 (en) * | 1994-10-31 | 1998-03-18 | 日清製粉株式会社 | Monoclonal antibody of human glicentin, hybridoma producing the antibody, and method for quantifying human glicentin using the same |
DE69535830D1 (en) | 1994-11-02 | 2008-10-16 | Trophix Pharm Inc | SODIUM ION CHANNELS SPECIFIC TO THE PERIPHERAL NERVOUS SYSTEM, DNA THAT CODES, ACTIVE SEARCH AND METHODS FOR THEIR PREPARATION AND USE |
US5837815A (en) * | 1994-12-15 | 1998-11-17 | Sugen, Inc. | PYK2 related polypeptide products |
US5837524A (en) * | 1994-12-15 | 1998-11-17 | Sugen, Inc. | PYK2 related polynucleotide products |
IL114615A0 (en) | 1995-07-16 | 1995-11-27 | Yeda Res & Dev | Modulators of the function of fas receptors and other proteins |
US5807989A (en) * | 1994-12-23 | 1998-09-15 | New York University | Methods for treatment or diagnosis of diseases or disorders associated with an APB domain |
US6300482B1 (en) * | 1995-01-03 | 2001-10-09 | Max-Flanck-Gesellschaft Zuer For{Overscore (D)}Erung Der | MDKI, a novel receptor tyrosine kinase |
US5569608A (en) * | 1995-01-30 | 1996-10-29 | Bayer Corporation | Quantitative detection of analytes on immunochromatographic strips |
US5783387A (en) * | 1995-02-06 | 1998-07-21 | The Regents Of The University Of California | Method for identifying and quantifying nucleic acid sequence aberrations |
US5731153A (en) * | 1996-08-26 | 1998-03-24 | The Regents Of The University Of California | Identification of random nucleic acid sequence aberrations using dual capture probes which hybridize to different chromosome regions |
US5874214A (en) * | 1995-04-25 | 1999-02-23 | Irori | Remotely programmable matrices with memories |
US5741462A (en) * | 1995-04-25 | 1998-04-21 | Irori | Remotely programmable matrices with memories |
US6329139B1 (en) | 1995-04-25 | 2001-12-11 | Discovery Partners International | Automated sorting system for matrices with memory |
US6331273B1 (en) | 1995-04-25 | 2001-12-18 | Discovery Partners International | Remotely programmable matrices with memories |
US6017496A (en) * | 1995-06-07 | 2000-01-25 | Irori | Matrices with memories and uses thereof |
US5751629A (en) * | 1995-04-25 | 1998-05-12 | Irori | Remotely programmable matrices with memories |
US6416714B1 (en) * | 1995-04-25 | 2002-07-09 | Discovery Partners International, Inc. | Remotely programmable matrices with memories |
US5686257A (en) * | 1995-04-26 | 1997-11-11 | Schering Corporation | Binding compositions for mammalian T cell antigens and related reagents |
US6147106A (en) * | 1997-08-20 | 2000-11-14 | Sugen, Inc. | Indolinone combinatorial libraries and related products and methods for the treatment of disease |
WO1997000271A1 (en) | 1995-06-14 | 1997-01-03 | The Regents Of The University Of California | Novel high affinity human antibodies to tumor antigens |
US6027879A (en) * | 1995-08-09 | 2000-02-22 | The Regents Of The University Of California | Detection and isolation of nucleic acid sequences using a bifunctional hybridization probe |
US5616465A (en) * | 1995-08-09 | 1997-04-01 | The Regents Of The University Of California | Detection and isolation of nucleic acid sequences using competitive hybridization probes |
US7635597B2 (en) * | 1995-08-09 | 2009-12-22 | Bayer Healthcare Llc | Dry reagent particle assay and device having multiple test zones and method therefor |
US5733728A (en) * | 1995-08-18 | 1998-03-31 | Regents Of The University Of Colorado | Detecting and treating heart failure |
US5660990A (en) * | 1995-08-18 | 1997-08-26 | Immunivest Corporation | Surface immobilization of magnetically collected materials |
US7455964B1 (en) | 1996-07-15 | 2008-11-25 | The Hospital For Sick Children | Genes from the 20q13 amplicon and their uses |
US7119174B2 (en) * | 1995-12-18 | 2006-10-10 | Sugen, Inc. | Diagnosis and treatment of AUR1 and/or AUR2 related disorders |
US5837492A (en) | 1995-12-18 | 1998-11-17 | Myriad Genetics, Inc. | Chromosome 13-linked breast cancer susceptibility gene |
US6716575B2 (en) | 1995-12-18 | 2004-04-06 | Sugen, Inc. | Diagnosis and treatment of AUR1 and/or AUR2 related disorders |
ES2325820T3 (en) | 1995-12-22 | 2009-09-18 | University Of Utah Research Foundation | GENE OF THE LONG QT SYNDROME CODING KVLQT1 AND ITS ASSOCIATION WITH MINK. |
US7888466B2 (en) | 1996-01-11 | 2011-02-15 | Human Genome Sciences, Inc. | Human G-protein chemokine receptor HSATU68 |
US5770086A (en) * | 1996-01-25 | 1998-06-23 | Eureka| Science Corp. | Methods and apparatus using hydrogels |
US5942385A (en) * | 1996-03-21 | 1999-08-24 | Sugen, Inc. | Method for molecular diagnosis of tumor angiogenesis and metastasis |
US6531578B1 (en) | 1996-04-12 | 2003-03-11 | Robert Webber | Immunoassay method employing monoclonal antibody reactive to human iNOS |
US5968839A (en) * | 1996-05-13 | 1999-10-19 | Metrika, Inc. | Method and device producing a predetermined distribution of detectable change in assays |
DE69740033D1 (en) | 1996-07-03 | 2010-12-09 | Merial Inc | RECOMBINANT DOG ADENOVIRUS 2 (CAV2), WHICH CONTAINS EXOGENOUS DNA |
US6524578B1 (en) | 1996-07-10 | 2003-02-25 | Scott E. Tackett | Use of nuclease to reduce wrinkles and discolorations in humans |
DE19629444A1 (en) * | 1996-07-22 | 1998-01-29 | Behringwerke Ag | Increased sensitivity in the immunochemical determination of an analyte |
US6297027B1 (en) | 1996-07-31 | 2001-10-02 | Purina Mills, Inc. | Bovine leptin protein, nucleic acid sequences coding therefor and uses thereof |
US6277592B1 (en) | 1996-07-31 | 2001-08-21 | Purina Mills, Inc. | Porcine leptin protein, nucleic acid sequences coding therefor and uses thereof |
US6159462A (en) * | 1996-08-16 | 2000-12-12 | Genentech, Inc. | Uses of Wnt polypeptides |
US5851984A (en) * | 1996-08-16 | 1998-12-22 | Genentech, Inc. | Method of enhancing proliferation or differentiation of hematopoietic stem cells using Wnt polypeptides |
US5945345A (en) * | 1996-08-27 | 1999-08-31 | Metrika, Inc. | Device for preventing assay interference using silver or lead to remove the interferant |
US6001658A (en) * | 1996-09-13 | 1999-12-14 | Diagnostic Chemicals Limited | Test strip apparatus and method for determining presence of analyte in a fluid sample |
US5856194A (en) | 1996-09-19 | 1999-01-05 | Abbott Laboratories | Method for determination of item of interest in a sample |
US5795784A (en) | 1996-09-19 | 1998-08-18 | Abbott Laboratories | Method of performing a process for determining an item of interest in a sample |
GB2321642B8 (en) | 1996-10-01 | 2006-08-22 | Geron Corp | Human telomerase reverse transcriptase promoter |
US6004791A (en) * | 1996-11-13 | 1999-12-21 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Protein tyrosine phosphatase PTP20 and related products and methods |
AU5754298A (en) * | 1996-12-09 | 1998-07-03 | Osteometer Biotech As | Sandwich assays for collagen type i fragments |
SI1019500T1 (en) | 1997-01-15 | 2007-02-28 | Yeda Res & Dev | Ifn receptor 1 binding proteins, dna encoding them, and methods of modulating cellular response to interferons |
US5879951A (en) * | 1997-01-29 | 1999-03-09 | Smithkline Diagnostics, Inc. | Opposable-element assay device employing unidirectional flow |
US20040241645A1 (en) * | 1997-01-31 | 2004-12-02 | Genentech, Inc. | O-fucosyltransferase |
EP0942992B1 (en) | 1997-01-31 | 2007-03-07 | Genentech, Inc. | O-fucosyltransferase |
DE69841160D1 (en) | 1997-02-07 | 2009-10-29 | Us Gov Health & Human Serv | ACTIVITY DEPENDENT NEUROTROPIC FACTOR III (ADNF III) |
US20050101032A1 (en) * | 1997-02-10 | 2005-05-12 | Metrika, Inc. | Assay device, composition, and method of optimizing assay sensitivity |
JP4245084B2 (en) | 1997-03-21 | 2009-03-25 | ストラタジーン | Polymerase enhancing factor (PEF) extract, PEF protein complex, isolated PEF protein, and purification and isolation methods |
US5955355A (en) * | 1997-03-27 | 1999-09-21 | Millennium Pharmaceuticals, Inc. | Chromosome 18 marker |
US5939316A (en) * | 1997-03-27 | 1999-08-17 | Millennium Pharmaceuticals, Inc. | Chromosome 18 marker |
US5866412A (en) * | 1997-03-27 | 1999-02-02 | Millennium Pharmaceuticals, Inc. | Chromosome 18 marker |
US5914394A (en) * | 1997-03-27 | 1999-06-22 | Millenium Pharmaceuticals, Inc. | Methods and compositions for the diagnosis and treatment of neuropsychiatric disorders |
WO1999021999A2 (en) | 1997-10-29 | 1999-05-06 | Genentech, Inc. | Wnt-1 inducible genes |
JP3957765B2 (en) | 1997-04-07 | 2007-08-15 | ジェネンテク・インコーポレイテッド | Anti-VEGF antibody |
ES2361267T3 (en) | 1997-04-07 | 2011-06-15 | Genentech Inc. | PROCEDURE FOR THE PRODUCTION OF HUMANIZED ANTIBODIES THROUGH RANDOM MUTAGENESIS. |
PT994728E (en) | 1997-04-09 | 2008-11-11 | Intellect Neurosciences Inc | Recombinant antibodies specific for beta-amyloid ends, dna encoding and methods of use thereof |
US6818440B2 (en) * | 1997-04-28 | 2004-11-16 | Sugen, Inc. | Diagnosis and treatment of alk-7 related disorders |
US6103536A (en) | 1997-05-02 | 2000-08-15 | Silver Lake Research Corporation | Internally referenced competitive assays |
US5939252A (en) * | 1997-05-09 | 1999-08-17 | Lennon; Donald J. | Detachable-element assay device |
US6228641B1 (en) | 1997-05-20 | 2001-05-08 | Sugen, Inc. | Diagnosis and treatment of PTP04 related disorders |
DE69842017D1 (en) | 1997-06-10 | 2011-01-05 | Lpath Inc | PROCEDURE FOR EARLY DETECTION OF DISEASES |
JP2002503963A (en) | 1997-06-11 | 2002-02-05 | ヒューマン・ジェノム・サイエンシズ・インコーポレイテッド | Human tumor necrosis factor receptor TR9 |
US7115710B2 (en) * | 1997-06-11 | 2006-10-03 | Sugen, Inc. | Diagnosis and treatment of PTP related disorders |
US6342593B1 (en) | 1997-06-11 | 2002-01-29 | Sugen, Inc. | Diagnosis and treatment of ALP related disorders |
US6388063B1 (en) | 1997-06-18 | 2002-05-14 | Sugen, Inc. | Diagnosis and treatment of SAD related disorders |
US6235769B1 (en) | 1997-07-03 | 2001-05-22 | Sugen, Inc. | Methods of preventing and treating neurological disorders with compounds that modulate the function of the C-RET receptor protein tyrosine kinase |
US6391547B1 (en) * | 1997-09-09 | 2002-05-21 | Center For The Application Of Molecular Biology To International Agriculture | Microbial β-glucuronidase genes, gene products and uses thereof |
US7087420B1 (en) | 1997-07-17 | 2006-08-08 | Cambia | Microbial β-glucuronidase genes, gene products and uses thereof |
US20040067531A1 (en) * | 1997-08-20 | 2004-04-08 | Sugen, Inc. | Methods of modulating protein tyrosine kinase function with substituted indolinone compounds |
US6960457B1 (en) * | 1997-09-04 | 2005-11-01 | Stanford University | Reversible immobilization of arginine-tagged moieties on a silicate surface |
US20140080177A1 (en) * | 1997-09-26 | 2014-03-20 | Pieris Ag | Anticalins |
KR20010015672A (en) * | 1997-09-29 | 2001-02-26 | 유니버시티 오브 메릴랜드, 볼티모어 | Altered DNA synthesome components as biomarkers for malignancy |
WO1999019466A2 (en) | 1997-10-14 | 1999-04-22 | Darwin Molecular Corporation | Thymidine kinase mutants and fusion proteins having thymidine kinase and guanylate kinase activities |
US6387657B1 (en) | 1997-10-29 | 2002-05-14 | Genentech, Inc. | WISP polypeptides and nucleic acids encoding same |
CA2309541C (en) | 1997-11-03 | 2011-01-11 | Human Genome Sciences, Inc. | Vegi, an inhibitor of angiogenesis and tumor growth |
US6224882B1 (en) | 1997-11-07 | 2001-05-01 | Protein Science Corp. | Insect cells or fractions as adjuvant for antigens |
US6437563B1 (en) | 1997-11-21 | 2002-08-20 | Quantum Design, Inc. | Method and apparatus for making measurements of accumulations of magnetically susceptible particles combined with analytes |
DE69837897T2 (en) | 1997-11-21 | 2008-03-06 | Genentech Inc., San Francisco | A33 related antigens and their pharmaceutical uses |
US7192589B2 (en) | 1998-09-16 | 2007-03-20 | Genentech, Inc. | Treatment of inflammatory disorders with STIgMA immunoadhesins |
US6221585B1 (en) | 1998-01-15 | 2001-04-24 | Valigen, Inc. | Method for identifying genes underlying defined phenotypes |
US6531502B1 (en) | 1998-01-21 | 2003-03-11 | Sugen, Inc. | 3-Methylidenyl-2-indolinone modulators of protein kinase |
CA2318403A1 (en) * | 1998-01-21 | 1999-07-29 | Sugen, Inc. | Human orthologues of wart |
US6764830B1 (en) | 1998-01-23 | 2004-07-20 | The Regents Of The University Of California | Thermomyces lanuginosus kinesin motor protein and methods of screening for modulators of kinesin proteins |
US6342351B1 (en) | 1998-03-16 | 2002-01-29 | Millennium Pharmaceuticals, Inc. | Methods and compositions for diagnosing and treating chromosome-18p related disorders |
US20040176572A1 (en) * | 1998-03-16 | 2004-09-09 | Freimer Nelson B. | Methods of compositions for diagnosing and treating chromosome-18p related disorders |
ES2389387T3 (en) | 1998-03-17 | 2012-10-25 | Genentech, Inc. | Homologous VEGF and BMP1 polypeptides |
US6514981B1 (en) * | 1998-04-02 | 2003-02-04 | Sugen, Inc. | Methods of modulating tyrosine protein kinase function with indolinone compounds |
US6274314B1 (en) * | 1998-04-02 | 2001-08-14 | Nyxis Neurotherapies, Inc. | Diagnostic assay for the modified nucleosides pseudouridine, 7-methyladenosine, or 1-methyladenosine |
DE69926742T2 (en) * | 1998-04-14 | 2006-06-14 | Sugen Inc | STE20-RELATED PROTEIN KINASES |
US7157083B2 (en) * | 1998-04-17 | 2007-01-02 | Surrogate Pharmaceutical Pathways, Llc | Compositions and methods for treating retroviral infections |
US20060019404A1 (en) * | 1998-05-06 | 2006-01-26 | Blatt Joel M | Quantitative assay with extended dynamic range |
DK1079824T3 (en) * | 1998-05-19 | 2011-11-21 | Res Dev Foundation | Triterpene compositions and methods for their use |
CA2331258C (en) | 1998-06-12 | 2011-09-20 | Henry M. Jackson Foundation For The Advancement Of Military Medicine | Enhancement of b cell activation and immunoglobulin secretion by co-stimulation of receptors for antigen and ebv gp350/220 |
EP1806362B1 (en) | 1998-07-28 | 2010-07-21 | The Regents of the University of California | Nucleic acids encoding a G-protein coupled receptor involved in sensory transduction |
US7402400B2 (en) | 2001-07-03 | 2008-07-22 | Regents Of The University Of California | Mammalian sweet taste receptors |
CA2340790C (en) * | 1998-08-21 | 2012-07-10 | Immunex Corporation | Human il-1 epsilon dna and polypeptides |
EP1030685A4 (en) | 1998-09-09 | 2001-04-25 | Millennium Pharm Inc | Essential bacterial genes and their use |
US20070178475A1 (en) * | 1998-09-17 | 2007-08-02 | Nehls Michael C | Novel human polynucleotides and polypeptides encoded thereby |
US6680335B2 (en) | 1998-09-28 | 2004-01-20 | Sugen, Inc. | Methods of modulating protein tyrosine kinase function with substituted indolinone compounds |
US6368793B1 (en) * | 1998-10-14 | 2002-04-09 | Microgenomics, Inc. | Metabolic selection methods |
US7091324B2 (en) | 1998-11-05 | 2006-08-15 | Board Of Trustees Of Leland Stanford Junior University | Prevention and treatment of HCV infection employing antibodies directed against conformational epitopes |
EP1950300A3 (en) | 1998-11-18 | 2011-03-23 | Genentech, Inc. | Antibody variants with higher binding affinity compared to parent antibodies |
US20040009535A1 (en) | 1998-11-27 | 2004-01-15 | Celltech R&D, Inc. | Compositions and methods for increasing bone mineralization |
NZ552959A (en) | 1998-11-27 | 2008-06-30 | Darwin Discovery Ltd | Compositions and methods for increasing bone mineralization |
US7273618B2 (en) * | 1998-12-09 | 2007-09-25 | Chiron Corporation | Method for administering agents to the central nervous system |
EP2016953A3 (en) | 1998-12-22 | 2009-04-15 | Genentech, Inc. | Vascular endothelial cell growth factor antagonists and uses thereof |
US6861442B1 (en) * | 1998-12-30 | 2005-03-01 | Sugen, Inc. | PYK2 and inflammation |
US20020031802A1 (en) * | 2000-05-12 | 2002-03-14 | Yi Hu | Novel seven transmembrane proteins and polynucleotides encoding the same |
US6570003B1 (en) * | 2001-01-09 | 2003-05-27 | Lexion Genetics Incorporated | Human 7TM proteins and polynucleotides encoding the same |
US20020061556A1 (en) * | 2000-04-27 | 2002-05-23 | Walke D. Wade | Novel membrane proteins and polynucleotides encoding the same |
US20020055626A1 (en) * | 2000-06-09 | 2002-05-09 | Turner C. Alexander | Novel human seven transmembrane proteins and polynucleotides encoding the same |
US20020103359A1 (en) * | 1999-12-07 | 2002-08-01 | Gregory Donoho | Novel human membrane proteins and polynucleotides encoding the same |
AU777909B2 (en) | 1999-01-19 | 2004-11-04 | Lexicon Genetics Incorporated | Mammalian cortexin-like proteins and polynucleotides encoding the same |
US7396810B1 (en) | 2000-08-14 | 2008-07-08 | Oregon Health Sciences University | Compositions and methods for treating cancer by modulating HER-2 and EGF receptors |
US7625859B1 (en) * | 2000-02-16 | 2009-12-01 | Oregon Health & Science University | HER-2 binding antagonists |
US7393823B1 (en) | 1999-01-20 | 2008-07-01 | Oregon Health And Science University | HER-2 binding antagonists |
US6303749B1 (en) | 1999-01-29 | 2001-10-16 | Amgen Inc. | Agouti and agouti-related peptide analogs |
CA2359747A1 (en) | 1999-02-09 | 2000-08-17 | Lexicon Genetics Incorporated | Human uncoupling proteins and polynucleotides encoding the same |
GB9903841D0 (en) * | 1999-02-20 | 1999-04-14 | Imp College Innovations Ltd | Diagnosis and treatment of cancer |
US6911429B2 (en) * | 1999-04-01 | 2005-06-28 | Transition Therapeutics Inc. | Compositions and methods for treating cellular response to injury and other proliferating cell disorders regulated by hyaladherin and hyaluronans |
US6864235B1 (en) * | 1999-04-01 | 2005-03-08 | Eva A. Turley | Compositions and methods for treating cellular response to injury and other proliferating cell disorders regulated by hyaladherin and hyaluronans |
US6844163B1 (en) | 1999-04-12 | 2005-01-18 | Sumitomo Chemical Co., Ltd. | Method for analyzing the amount of intraabdominal adipose tissue |
US20080145347A1 (en) * | 1999-04-29 | 2008-06-19 | Steiner Mitchell S | p-Hyde sequences in the Rat |
US20020110809A1 (en) * | 1999-04-30 | 2002-08-15 | Nehls Michael C. | Novel human polynucleotides and polypeptides encoded thereby |
US7566452B1 (en) | 1999-05-04 | 2009-07-28 | New York University | Cancer treatment with endothelin receptor antagonists |
US20020095031A1 (en) * | 1999-05-04 | 2002-07-18 | Nehls Michael C. | Novel human polynucleotides and polypeptides encoded thereby |
US20030186311A1 (en) * | 1999-05-21 | 2003-10-02 | Bioforce Nanosciences, Inc. | Parallel analysis of molecular interactions |
IL130225A0 (en) | 1999-05-31 | 2000-06-01 | Yissum Res Dev Co | Novel uses of antibodies against ache and peptides thereof |
JP2003507055A (en) * | 1999-08-24 | 2003-02-25 | レキシコン・ジェネティクス・インコーポレーテッド | Sequence obtained from human mammary gland cDNA library |
NZ523206A (en) * | 1999-08-31 | 2004-12-24 | Genentech Inc | Antibodies that bind to tumor gene sequences |
US6448388B1 (en) | 2000-08-16 | 2002-09-10 | Lexicon Genetics Incorporated | Human proteases and polynucleotides encoding the same |
US20020165376A1 (en) * | 1999-12-22 | 2002-11-07 | Walke D. Wade | Novel human proteases and polynucleotides encoding the same |
US6433153B1 (en) | 1999-09-02 | 2002-08-13 | Lexicon Genetics Incorporated | Human calcium dependent proteases and polynucleotides encoding the same |
US6716614B1 (en) | 1999-09-02 | 2004-04-06 | Lexicon Genetics Incorporated | Human calcium dependent proteases, polynucleotides encoding the same, and uses thereof |
US20010034437A1 (en) * | 2000-01-06 | 2001-10-25 | Walke D. Wade | Novel human proteases and polynucleotides encoding the same |
US20020049312A1 (en) * | 2000-05-23 | 2002-04-25 | Turner C. Alexander | Noel human thrombospondin-like proteins and polynucleotides encoding the same |
US20030050464A1 (en) * | 2000-07-28 | 2003-03-13 | Yi Hu | Novel human proteases and polynucleotides encoding the same |
US20080003673A1 (en) * | 1999-09-02 | 2008-01-03 | Alejandro Abuin | Novel human proteases and polynucleotides encoding the same |
US20050153323A1 (en) * | 2000-07-28 | 2005-07-14 | Yi Hu | Novel human proteases and polynucleotides encoding the same |
US7459540B1 (en) * | 1999-09-07 | 2008-12-02 | Amgen Inc. | Fibroblast growth factor-like polypeptides |
US7408047B1 (en) * | 1999-09-07 | 2008-08-05 | Amgen Inc. | Fibroblast growth factor-like polypeptides |
JP2003508076A (en) * | 1999-09-08 | 2003-03-04 | レキシコン・ジェネティクス・インコーポレーテッド | Seven-transmembrane receptor coupled to human G protein and polynucleotide encoding the same |
AU780935B2 (en) | 1999-09-13 | 2005-04-28 | Equitech Laboratories, Inc. | Materials and methods for the determination of an analyte |
US6900043B1 (en) * | 1999-09-21 | 2005-05-31 | Amgen Inc. | Phosphatases which activate map kinase pathways |
US20020107382A1 (en) * | 2000-09-27 | 2002-08-08 | Friddle Carl Johan | Novel human protease inhibitor proteins and polynucleotides encoding the same |
CA2385813A1 (en) * | 1999-09-24 | 2001-03-29 | Lexicon Genetics Incorporated | Human endothelin converting enzyme-like proteins and polynucleotides encoding the same |
EP1633872A2 (en) * | 1999-09-24 | 2006-03-15 | Lexicon Genetics Incorporated | Novel human protease inhibitor-like proteins and polynucleotides encoding the same |
US20030166883A1 (en) * | 2000-11-15 | 2003-09-04 | Walke D. Wade | Novel human secreted proteins and polynucleotides encoding the same |
US6790660B1 (en) * | 2001-09-18 | 2004-09-14 | Lexicon Genetics Incorporated | Human kielin-like proteins and polynucleotides encoding the same |
US6867291B1 (en) * | 2000-09-15 | 2005-03-15 | Lexicon Genetics Incorporated | Human hemicentin proteins and polynucleotides encoding the same |
US6586230B1 (en) * | 2000-10-27 | 2003-07-01 | Lexicon Genetics Incorporated | Human kinase and polynucleotides encoding the same |
US6716616B1 (en) | 1999-09-28 | 2004-04-06 | Lexicon Genetics Incorporated | Human kinase proteins and polynucleotides encoding the same |
US20080050809A1 (en) * | 1999-09-28 | 2008-02-28 | Alejandro Abuin | Novel human kinases and polynucleotides encoding the same |
US6797510B1 (en) | 2001-05-24 | 2004-09-28 | Lexicon Genetics Incorporated | Human kinases and polynucleotides encoding the same |
US6511840B1 (en) | 2000-06-15 | 2003-01-28 | Lexicon Genetics Incorporated | Human kinase proteins and polynucleotides encoding the same |
US6541252B1 (en) | 2000-05-19 | 2003-04-01 | Lexicon Genetics Incorporated | Human kinases and polynucleotides encoding the same |
US6900045B2 (en) * | 2000-08-31 | 2005-05-31 | Lexicon Genetics Incorporated | Human kinase proteins and polynucleotides encoding the same |
US6759527B2 (en) | 2001-03-20 | 2004-07-06 | Lexicon Genetics Incorporated | Human kinase and polynucleotides encoding the same |
US6841377B1 (en) * | 2001-06-13 | 2005-01-11 | Lexicon Genetics Incorporated | Human kinase and polynucleotides encoding the same |
US6734010B2 (en) * | 2001-05-09 | 2004-05-11 | Lexicon Genetics Incorporated | Human kinases and polynucleotides encoding the same |
US6720173B1 (en) | 1999-11-08 | 2004-04-13 | Lexicon Genetics Incorporated | Human kinase protein and polynucleotides encoding the same |
CA2385883A1 (en) | 1999-09-29 | 2001-04-05 | Lexicon Genetics Incorporated | Human carboxypeptidases and polynucleotides encoding the same |
US20070111259A1 (en) * | 1999-10-02 | 2007-05-17 | Medarex, Inc. | Human antibodies |
US7135287B1 (en) | 1999-10-02 | 2006-11-14 | Biosite, Inc. | Human antibodies |
US6794132B2 (en) | 1999-10-02 | 2004-09-21 | Biosite, Inc. | Human antibodies |
AU782326B2 (en) | 1999-10-12 | 2005-07-21 | Lexicon Pharmaceuticals, Inc. | Human LDL receptor family proteins and polynucleotides encoding the same |
AU1198701A (en) * | 1999-10-13 | 2001-04-23 | Lexicon Genetics Incorporated | Novel human membrane proteins |
AU784052B2 (en) * | 1999-10-18 | 2006-01-19 | Lexicon Genetics Incorporated | Novel human proteins and polynucleotides encoding the same |
US20080213878A1 (en) * | 1999-10-19 | 2008-09-04 | Gregory Donoho | Novel human membrane proteins and polynucleotides encoding the same |
US6743907B1 (en) * | 1999-10-19 | 2004-06-01 | Lexicon Genetics Incorporated | Human proteins and polynucleotides encoding the same |
US6750054B2 (en) | 2000-05-18 | 2004-06-15 | Lexicon Genetics Incorporated | Human semaphorin homologs and polynucleotides encoding the same |
AU783313B2 (en) | 1999-11-02 | 2005-10-13 | Lexicon Pharmaceuticals, Inc. | Novel human transporter proteins and polynucleotides encoding the same |
WO2001034778A2 (en) * | 1999-11-10 | 2001-05-17 | Lexicon Genetics Incorporated | Human atpases and polynucleotides encoding the same |
EP1242588A2 (en) | 1999-11-12 | 2002-09-25 | Lexicon Genetics Incorporated | Human proteins with homology to carboxypeptidases and polynucleotides encoding the same |
ATE315789T1 (en) | 1999-11-16 | 2006-02-15 | Genentech Inc | ELISA FOR VEGF |
US6943010B1 (en) * | 1999-11-19 | 2005-09-13 | Hortense W. Dodo | Down-regulation and silencing of allergen genes in transgenic peanut seeds |
ES2629683T3 (en) | 1999-11-30 | 2017-08-14 | Mayo Foundation For Medical Education And Research | B7-H1, a new immunoregulatory molecule |
US6680209B1 (en) | 1999-12-06 | 2004-01-20 | Biosite, Incorporated | Human antibodies as diagnostic reagents |
EP1240187A2 (en) | 1999-12-07 | 2002-09-18 | Lexicon Genetics Incorporated | Novel human kinase proteins and polynucleotides encoding the same |
CA2393723A1 (en) | 1999-12-09 | 2001-06-14 | Lexicon Genetics Incorporated | Human adam-ts proteases and polynucleotides encoding the same |
EP1263966A1 (en) * | 1999-12-13 | 2002-12-11 | Lexicon Genetics Incorporated | Novel human transferase proteins and polynucleotides encoding the same |
CA2395247A1 (en) * | 1999-12-22 | 2001-06-28 | Lexicon Genetics Incorporated | Novel human membrane proteins and polynucleotides encoding the same |
US20020010203A1 (en) | 1999-12-22 | 2002-01-24 | Ken Lipson | Methods of modulating c-kit tyrosine protein kinase function with indolinone compounds |
DK1897944T3 (en) | 1999-12-23 | 2011-10-24 | Genentech Inc | IL-17 homologous polypeptides and their therapeutic use |
WO2001053493A2 (en) | 2000-01-18 | 2001-07-26 | Lexicon Genetics Incorporated | Human kinase protein and polynucleotides encoding the same |
AU2001253117B8 (en) * | 2000-01-26 | 2006-08-03 | Lexicon Pharmaceuticals, Inc. | Human neurexin-like proteins and polynucleotides encoding the same |
US20020115837A1 (en) * | 2000-01-28 | 2002-08-22 | Turner C. Alexander | Novel human membrane proteins and polynucleotides encoding the same |
AU9256001A (en) * | 2000-01-28 | 2001-12-17 | Lexicon Genetics Incorporated | Novel human enzymes and polynucleotides encoding the same |
AU3665901A (en) * | 2000-02-04 | 2001-08-14 | Lexicon Genetics Incorporated | Novel human enzymes and polynucleotides encoding the same |
WO2001057086A2 (en) * | 2000-02-04 | 2001-08-09 | Lexicon Genetics Incorporated | Novel human g protein coupled receptor proteins and polynucleotides encoding the same |
JP2003522530A (en) * | 2000-02-11 | 2003-07-29 | レキシコン・ジェネティクス・インコーポレーテッド | Novel human protease and polynucleotide encoding the protease |
PT1255752E (en) * | 2000-02-15 | 2007-10-17 | Pharmacia & Upjohn Co Llc | Pyrrole substituted 2-indolinone protein kinase inhibitors |
AU2001238503A1 (en) * | 2000-02-17 | 2001-08-27 | Lexicon Genetics Incorporated | Novel human thrombospondin repeat proteins and polynucleotides encoding the same |
EP1259610A2 (en) | 2000-02-29 | 2002-11-27 | Lexicon Genetics Incorporated | Human transporter proteins and polynucleotides encoding the same |
US6555669B2 (en) * | 2000-02-29 | 2003-04-29 | Lexicon Genetics Incorporated | Human transferase proteins and polynucleotides encoding the same |
US20040002068A1 (en) | 2000-03-01 | 2004-01-01 | Corixa Corporation | Compositions and methods for the detection, diagnosis and therapy of hematological malignancies |
US20020082405A1 (en) * | 2000-03-06 | 2002-06-27 | Gregory Donoho | Novel human transporter proteins and polynucleotides encoding the same |
TW201006846A (en) | 2000-03-07 | 2010-02-16 | Senomyx Inc | T1R taste receptor and genes encidung same |
WO2001068869A2 (en) * | 2000-03-10 | 2001-09-20 | Lexicon Genetics Incorporated | Human g-coupled protein receptor kinsaes and polynucleotides encoding the same |
WO2001068871A2 (en) * | 2000-03-13 | 2001-09-20 | Lexicon Genetics Incorporated | Human phospholipases and polynucleotides encoding the same |
AU2001250898A1 (en) * | 2000-03-17 | 2001-10-03 | The Salk Institute For Biological Studies | Compositions associated with complex formation |
WO2001070806A2 (en) * | 2000-03-20 | 2001-09-27 | Lexicon Genetics Incorporated | Human secreted proteins and polynucleotides encoding the same |
AU2001218871A1 (en) * | 2000-03-21 | 2001-10-03 | Takao Arai | Monoclonal antibody and method and kit for the immunoassay of soluble human st2 with the use of the same |
US7514239B2 (en) | 2000-03-28 | 2009-04-07 | Amgen Inc. | Nucleic acid molecules encoding beta-like glycoprotein hormone polypeptides and heterodimers thereof |
WO2001074404A2 (en) | 2000-03-31 | 2001-10-11 | Novarx | Compositions containing genetically modified lung cancer cells expressing a tgf-beta inhibitor |
JP2004505610A (en) * | 2000-04-03 | 2004-02-26 | レキシコン・ジェネティクス・インコーポレーテッド | Novel human ion channel protein and polynucleotide encoding the same |
EP1272644A1 (en) * | 2000-04-12 | 2003-01-08 | Lexicon Genetics Incorporated | Human metalloprotease and polynucleotides encoding the same |
US7364867B2 (en) * | 2000-04-17 | 2008-04-29 | The Mount Sinai School Of Medicine | Method of identifying bitter compounds by employing TRP8, a transient receptor potential channel expressed in taste receptor cells |
WO2001081557A2 (en) | 2000-04-25 | 2001-11-01 | Lexicon Genetics Incorporated | Human kinase proteins and polynucleotides encoding the same |
US7030219B2 (en) * | 2000-04-28 | 2006-04-18 | Johns Hopkins University | B7-DC, Dendritic cell co-stimulatory molecules |
DK2026073T3 (en) | 2000-04-29 | 2016-07-25 | Univ Iowa Res Found | Diagnosis and treatment of macular degeneration-related disorders |
US20020107375A1 (en) * | 2000-05-12 | 2002-08-08 | Brian Mathur | Novel human lipocalin homologs and polynucleotides encoding the same |
EP1290162A4 (en) * | 2000-05-17 | 2005-08-17 | Univ Oregon Health Sciences | Induction of apoptosis and cell growth inhibition by protein 4.33 |
US6790667B1 (en) | 2000-05-30 | 2004-09-14 | Lexicon Genetics Incorporated | Human mitochondrial proteins and polynucleotides encoding the same |
WO2001094583A2 (en) * | 2000-06-07 | 2001-12-13 | Lexicon Genetics Incorporated | Human transporter proteins and polynucleotides encoding the same |
US6465632B1 (en) | 2000-06-09 | 2002-10-15 | Lexicon Genetics Incorporated | Human phosphatases and polynucleotides encoding the same |
US20040168209A1 (en) * | 2000-06-12 | 2004-08-26 | Alejandro Abuin | Novel murine polynucleotide sequences and mutant cells and mutant animals defined thereby |
AU2001282856A1 (en) | 2000-06-15 | 2001-12-24 | Human Genome Sciences, Inc. | Human tumor necrosis factor delta and epsilon |
AU7296801A (en) | 2000-06-22 | 2002-02-05 | Amgen Inc | Il-17 molecules and uses thereof |
CA2648046A1 (en) | 2000-06-23 | 2002-01-03 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of disorders involving angiogenesis |
EP2275549A1 (en) | 2000-06-23 | 2011-01-19 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of disorders involving angiogenesis |
US6528321B1 (en) | 2000-06-26 | 2003-03-04 | Beckman Coulter, Inc. | Opposable-element chromatographic assay device for detection of analytes in whole blood samples |
US20030032791A1 (en) * | 2000-06-26 | 2003-02-13 | Alan Robertson Scott | Novel melanocortin-4 receptor sequences and screening assays to identify compounds useful in regulating animal appetite and metabolic rate |
EP1297134A2 (en) * | 2000-06-27 | 2003-04-02 | Lexicon Genetics Incorporated | Novel human gaba receptors and polynucleotides encoding the same |
AU7026601A (en) | 2000-06-28 | 2002-01-08 | Amgen Inc | Thymic stromal lymphopoietin receptor molecules and uses thereof |
US20060257399A1 (en) * | 2000-06-28 | 2006-11-16 | Glycofi, Inc. | Immunoglobulins comprising predominantly a Man5GIcNAc2 glycoform |
US20060024304A1 (en) * | 2000-06-28 | 2006-02-02 | Gerngross Tillman U | Immunoglobulins comprising predominantly a Man5GlcNAc2 glycoform |
US20060029604A1 (en) * | 2000-06-28 | 2006-02-09 | Gerngross Tillman U | Immunoglobulins comprising predominantly a GlcNAc2Man3GlcNAc2 glycoform |
US20060034828A1 (en) * | 2000-06-28 | 2006-02-16 | Gerngross Tillman U | Immunoglobulins comprising predominantly a GlcNAcMAN5GLCNAC2 glycoform |
US20060034830A1 (en) * | 2000-06-28 | 2006-02-16 | Gerngross Tillman U | Immunoglobulins comprising predominantly a GalGlcNAcMan5GLcNAc2 glycoform |
JP2004515220A (en) * | 2000-07-21 | 2004-05-27 | インサイト・ゲノミックス・インコーポレイテッド | Protease |
US6632681B1 (en) | 2000-07-24 | 2003-10-14 | Ey Laboratories | Reagent delivery device and method of use |
US6887685B1 (en) | 2000-07-25 | 2005-05-03 | Lexicon Genetics Incorporated | Human thymosin protein and polynucleotides encoding the same |
US20020076780A1 (en) * | 2000-08-16 | 2002-06-20 | Turner C. Alexander | Novel human ion channel proteins and polynucleotides encoding the same |
US6680059B2 (en) * | 2000-08-29 | 2004-01-20 | Tripep Ab | Vaccines containing ribavirin and methods of use thereof |
US7022830B2 (en) * | 2000-08-17 | 2006-04-04 | Tripep Ab | Hepatitis C virus codon optimized non-structural NS3/4A fusion gene |
EP2332574A1 (en) | 2000-08-17 | 2011-06-15 | Tripep Ab | HCV NS3/4A Sequences |
RU2286172C2 (en) * | 2000-08-17 | 2006-10-27 | Трипеп Аб | Ribavirin-containing vaccines and methods for their application |
EP1311690B1 (en) * | 2000-08-22 | 2006-07-26 | Lexicon Genetics Incorporated | Human proteases and polynucleotides encoding the same |
WO2002016435A2 (en) * | 2000-08-22 | 2002-02-28 | Lexicon Genetics Incorporated | Human 7tm proteins and polynucleotides encoding the same |
BR0113512A (en) | 2000-08-25 | 2005-05-10 | Basf Plant Science Gmbh | Plant polynucleotides encoding new prenyl proteases |
EP1197550A3 (en) * | 2000-08-25 | 2002-11-20 | Pfizer Products Inc. | Methods and compositions for diagnosing and treating disorders involving angiogenesis |
US6803211B2 (en) | 2000-08-25 | 2004-10-12 | Pfizer Inc. | Methods and compositions for diagnosing and treating disorders involving angiogenesis |
EP1320551A4 (en) * | 2000-09-01 | 2006-12-20 | Internat Bioimmune Systems Inc | The identification and development of specific monoclonal antibodies to squamous cell carcinoma |
WO2002020753A2 (en) * | 2000-09-01 | 2002-03-14 | Lexicon Genetics Incorporated | Human gaba transporter protein and polynucleotides encoding the same |
US20030176344A1 (en) * | 2000-09-14 | 2003-09-18 | Decode Genetics Ehf. | Human osteoporosis gene |
US7186521B2 (en) * | 2000-09-25 | 2007-03-06 | The Regents Of The University Of California | Determining the effect of a substance on sequestration, uptake, and accumulation of amyloid in brain cells |
ATE326533T1 (en) | 2000-09-27 | 2006-06-15 | Lexicon Genetics Inc | HUMAN ION EXCHANGE PROTEINS AND POLYNUcleotides Encoding Therefor |
US6777232B1 (en) * | 2000-10-02 | 2004-08-17 | Lexicon Genetics Incorporated | Human membrane proteins and polynucleotides encoding the same |
WO2002033089A2 (en) * | 2000-10-05 | 2002-04-25 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Ixodes scapularis tissue factor pathway inhibitor |
AU2002213183A1 (en) | 2000-10-12 | 2002-04-22 | Lexicon Genetics Incorporated | Human kinases and polynucleotides encoding the same |
US7001763B1 (en) | 2000-10-17 | 2006-02-21 | Lexicon Genetics Incorporated | Human semaphorin proteins and polynucleotides encoding the same |
US20040048274A1 (en) * | 2000-10-17 | 2004-03-11 | Morten Breindahl | Assay for directly detecting an inflammatory indicator in a body fluid sample |
EP1409674A2 (en) * | 2000-10-27 | 2004-04-21 | Lexicon Genetics Incorporated | Human 7tm proteins and polynucleotides encoding them |
US7232880B2 (en) * | 2000-10-27 | 2007-06-19 | Oregon Health & Science University | Mutant IGFBP-3 molecules that do not bind to IGFS, but retain their ability to functionally bind IGFBP-3 receptor |
CA2427701A1 (en) * | 2000-10-30 | 2002-05-10 | Lexicon Genetics Incorporated | Human 7tm proteins and polynucleotides encoding the same |
WO2002036759A2 (en) * | 2000-11-01 | 2002-05-10 | Lexicon Genetics Incorporated | Polynucleotides encoding human meltrin beta (adam19) metalloendopeptidases |
US20060148732A1 (en) * | 2000-11-17 | 2006-07-06 | Gutterman Jordan U | Inhibition of NF-kappaB by triterpene compositions |
AU2002228633A1 (en) * | 2000-11-20 | 2002-06-03 | Lexicon Genetics Incorporated | Human kinases and polynucleotides encoding the same |
US6989247B2 (en) | 2000-11-28 | 2006-01-24 | Celltech R & D, Inc. | Compositions and methods for diagnosing or treating psoriasis |
US7393921B2 (en) * | 2000-12-04 | 2008-07-01 | Institute For Systems Biology | Prostate-specific polypeptide pamp and encoding nucleic acid molecules |
US9249229B2 (en) * | 2000-12-08 | 2016-02-02 | Alexion Pharmaceuticals, Inc. | Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof |
US20040198661A1 (en) * | 2000-12-08 | 2004-10-07 | Bowdish Katherine S. | Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof |
EP1341902A2 (en) * | 2000-12-08 | 2003-09-10 | Alexion Pharmaceuticals, Inc. | Chronic lymphocytic leukemia cell line and its use for producing an antibody |
US20060057651A1 (en) * | 2000-12-08 | 2006-03-16 | Bowdish Katherine S | Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof |
US7408041B2 (en) | 2000-12-08 | 2008-08-05 | Alexion Pharmaceuticals, Inc. | Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof |
CA2431007A1 (en) * | 2000-12-11 | 2002-07-18 | Lexicon Genetics Incorporated | Novel human kinase and polynucleotides encoding the same |
WO2002048333A2 (en) * | 2000-12-12 | 2002-06-20 | Lexicon Genetics Incorporated | Novel human kinases and uses thereof |
US6583269B1 (en) | 2000-12-18 | 2003-06-24 | Lexicon Genetics Incorporated | Human protease inhibitor and polynucleotides encoding the same |
US6852844B1 (en) | 2000-12-20 | 2005-02-08 | Lexicon Genetics Incorporated | Human protocadherin proteins and polynucleotides encoding the same |
CA2432737A1 (en) * | 2000-12-20 | 2002-06-27 | Lexicon Genetics Incorporated | Human ion channel protein and polynucleotides encoding the same |
IL140537A0 (en) * | 2000-12-25 | 2002-02-10 | Hadasit Med Res Service | Educated nk t cells and their uses in the treatment of immune-related disorders |
US7445802B2 (en) * | 2000-12-26 | 2008-11-04 | Yeda Research And Development Co. Ltd | Site-specific in situ generation of allicin using a targeted alliinase delivery system for the treatment of cancers, tumors, infectious diseases and other allicin-sensitive diseases |
AU2002246858A1 (en) * | 2000-12-27 | 2002-08-06 | Lexicon Genetics Incorporated | Human kinases and polynucleotides encoding the same |
AU2001297533A1 (en) * | 2000-12-28 | 2002-09-12 | Lexicon Genetics Incorporated | Novel human ion channel-related proteins and polynucleotides encoding the same |
TW201022287A (en) | 2001-01-03 | 2010-06-16 | Senomyx Inc | T1R taste receptors and genes encoding same |
US20020115844A1 (en) * | 2001-01-05 | 2002-08-22 | Yu Xuanchuan Sean | Novel human lipase and polynucleotides encoding the same |
WO2002053754A2 (en) * | 2001-01-08 | 2002-07-11 | Lexicon Genetics Incorporated | Human protease and polynucleotides encoding the same |
EP1407029A2 (en) * | 2001-01-23 | 2004-04-14 | Lexicon Genetics Incorporated | Novel human kinases and polynucleotides encoding the same |
JP2005502311A (en) * | 2001-01-24 | 2005-01-27 | レキシコン・ジェネティクス・インコーポレーテッド | Novel human lipase and polynucleotide encoding the lipase |
US20020127674A1 (en) * | 2001-02-02 | 2002-09-12 | Xuanchuan Yu | Novel human transporter protein and polynucleotides encoding the same |
IL157350A0 (en) | 2001-02-14 | 2004-02-19 | Anthrogenesis Corp | Post-partum mammalian placenta, its use and placental stem cells therefrom |
AR042586A1 (en) | 2001-02-15 | 2005-06-29 | Sugen Inc | 3- (4-AMIDOPIRROL-2-ILMETILIDEN) -2-INDOLINONE AS INHIBITORS OF PROTEIN KINASE; YOUR PHARMACEUTICAL COMPOSITIONS; A METHOD FOR THE MODULATION OF THE CATALYTIC ACTIVITY OF PROTEINQUINASE; A METHOD TO TREAT OR PREVENT AN AFFECTION RELATED TO PROTEINQUINASE |
WO2002066624A2 (en) * | 2001-02-20 | 2002-08-29 | Lexicon Genetics Incorporated | Novel human protease and polynucleotides encoding the same |
US20020117169A1 (en) | 2001-02-27 | 2002-08-29 | Kurz Daniel R. | Cover and applicator for a portion of a mammalian body |
JP3929250B2 (en) * | 2001-03-08 | 2007-06-13 | 株式会社ルネサステクノロジ | Semiconductor device |
AU2002252296A1 (en) * | 2001-03-12 | 2002-09-24 | Lexicon Genetics Incorporated | Novel human transporter proteins and polynucleotides encoding the same |
AU2002245593A1 (en) * | 2001-03-12 | 2002-09-24 | Lexicon Genetics Incorporated | Novel human dectin proteins and polynucleotides encoding the same |
JP2004535781A (en) * | 2001-03-12 | 2004-12-02 | レキシコン・ジェネティクス・インコーポレーテッド | Novel human EFG family protein and polynucleotide encoding the same |
CA2441042A1 (en) | 2001-03-15 | 2002-09-26 | International Bioimmune Systems, Inc. | Monoclonal antibody therapy for pancreas cancer |
US6994995B1 (en) | 2001-03-16 | 2006-02-07 | Lexicon Genetics Incorporated | Human synaptotagmin and polynucleotides encoding the same |
US20030228639A1 (en) * | 2001-03-19 | 2003-12-11 | Wright George L | Prostate cancer markers |
US6613534B2 (en) | 2001-03-20 | 2003-09-02 | Wake Forest University Health Sciences | MAP-2 as a determinant of metastatic potential |
US7071303B2 (en) | 2001-03-28 | 2006-07-04 | Institute For Systems Biology | Androgen regulated prostate specific nucleic acids |
EP1383880A1 (en) * | 2001-04-06 | 2004-01-28 | Lexicon Genetics Incorporated | Novel human kinase and polynucleotides encoding the same |
WO2002081670A1 (en) * | 2001-04-06 | 2002-10-17 | Lexicon Genetics Incorporated | Novel human kinases and polynucleotides encoding the same |
EP2341148A3 (en) | 2001-04-12 | 2012-05-30 | Imperial Innovations Limited | Diagnosis and treatment of cancer |
KR100923598B1 (en) * | 2001-04-13 | 2009-10-23 | 와이어쓰 | Surface Proteins of Streptococcus pyogenes |
US20070128229A1 (en) * | 2002-04-12 | 2007-06-07 | Wyeth | Surface proteins of Streptococcus pyogenes |
US6607895B2 (en) | 2001-04-16 | 2003-08-19 | Lexicon Genetics Incorporated | Human adenylsuccinate synthetase and polynucleotides encoding the same |
US7803982B2 (en) | 2001-04-20 | 2010-09-28 | The Mount Sinai School Of Medicine Of New York University | T1R3 transgenic animals, cells and related methods |
EP1572871A4 (en) * | 2001-04-20 | 2007-11-14 | Sinai School Medicine | T1r3 a novel taste receptor |
US20030166893A1 (en) * | 2001-04-30 | 2003-09-04 | Yi Hu | Novel human nuclear transporters and polynucleotides encoding the same |
US20030211464A1 (en) * | 2001-05-02 | 2003-11-13 | Charles Pidgeon | Method and compositions for drug discovery |
WO2002090600A2 (en) | 2001-05-08 | 2002-11-14 | Darwin Molecular Corporation | A method for regulating immune function in primates using the foxp3 protein |
WO2002097095A1 (en) * | 2001-05-25 | 2002-12-05 | Lexicon Genetics Incorporated | Novel human transporter proteins and polynucleotides encoding the same |
AU2002303879B2 (en) | 2001-05-29 | 2007-08-09 | Lexicon Pharmaceuticals, Inc. | Novel human hydroxylases and polynucleotides encoding the same |
US7045605B2 (en) | 2001-06-01 | 2006-05-16 | Cornell Research Foundation, Inc. | Modified antibodies to prostate-specific membrane antigen and uses thereof |
US20070160576A1 (en) | 2001-06-05 | 2007-07-12 | Genentech, Inc. | IL-17A/F heterologous polypeptides and therapeutic uses thereof |
US7235358B2 (en) * | 2001-06-08 | 2007-06-26 | Expression Diagnostics, Inc. | Methods and compositions for diagnosing and monitoring transplant rejection |
US7026121B1 (en) * | 2001-06-08 | 2006-04-11 | Expression Diagnostics, Inc. | Methods and compositions for diagnosing and monitoring transplant rejection |
US6905827B2 (en) | 2001-06-08 | 2005-06-14 | Expression Diagnostics, Inc. | Methods and compositions for diagnosing or monitoring auto immune and chronic inflammatory diseases |
WO2002102986A2 (en) * | 2001-06-14 | 2002-12-27 | Lexicon Genetics Incorporated | Novel human transporter proteins and polynucleotides encoding the same |
WO2003000010A2 (en) * | 2001-06-20 | 2003-01-03 | Mayo Foundation For Medical Education And Research | Adenosyl-cobalamin fortified compositions |
WO2002102973A2 (en) * | 2001-06-20 | 2002-12-27 | Prochon Biotech Ltd. | Antibodies that block receptor protein tyrosine kinase activation, methods of screening for and uses thereof |
US20020197694A1 (en) * | 2001-06-20 | 2002-12-26 | Weiping Shao | Conjugates of reduced antibodies and biomolecules |
WO2003001876A2 (en) | 2001-06-26 | 2003-01-09 | Senomyx, Inc. | T1r hetero-oligomeric taste receptors and cell lines that express said receptors and use thereof for identification of taste compounds |
WO2003004609A2 (en) * | 2001-07-03 | 2003-01-16 | Lexicon Genetics Incorporated | Novel human kielin-like proteins and polynucleotides encoding the same |
US7270959B2 (en) | 2001-07-25 | 2007-09-18 | Oakville Hong Kong Company Limited | Specimen collection container |
US7300633B2 (en) * | 2001-07-25 | 2007-11-27 | Oakville Hong Kong Company Limited | Specimen collection container |
JP4265149B2 (en) * | 2001-07-25 | 2009-05-20 | セイコーエプソン株式会社 | Electro-optical device and method for manufacturing electro-optical device |
AUPR673001A0 (en) | 2001-07-31 | 2001-08-23 | Prince Henry's Institute Of Medical Research | Pregnancy-related enzyme activity |
US7744888B2 (en) | 2001-08-03 | 2010-06-29 | Abgenomics Cooperatief U.A. | Methods of modulating T cell or natural killer cell activity with anti-P-selectin glycoprotein ligand 1 antibodies |
AU2002365248A1 (en) | 2001-08-09 | 2003-09-02 | Cornell Research Foundation, Inc. | Detection of bovine viral diarrhea virus in hair samples |
EP1425382A4 (en) * | 2001-08-14 | 2004-10-06 | Lexicon Genetics Inc | Novel human collagen proteins and polynucleotides encoding the same |
AU2002324792A1 (en) * | 2001-08-27 | 2003-03-10 | Tularik Inc. | Amplified gene involved in cancer |
EP1423427A2 (en) * | 2001-08-27 | 2004-06-02 | Novartis AG | Nogo receptor homologues and their use |
US20030092042A1 (en) * | 2001-08-27 | 2003-05-15 | David Mu | Amplified oncogenes and their involvement in cancer |
JP2003076656A (en) * | 2001-09-05 | 2003-03-14 | Sony Corp | Information processing system, information processor and information processing method, recording medium and program |
AU2002326939A1 (en) | 2001-09-18 | 2003-04-01 | Fibrogen, Inc. | Methods of assaying connective tissue growth factor |
ATE443259T1 (en) | 2001-09-20 | 2009-10-15 | Univ Texas | DETERMINATION OF CIRCULATIVE THERAPEUTIC ANTIBODIES, ANTIGENS AND ANTIGEN-ANTIBODY COMPLEXES USING ELISA TESTS |
JP4554206B2 (en) * | 2001-09-27 | 2010-09-29 | ガンガゲン インコーポレーティッド | Neutralized whole cell immunogenic bacterial composition |
JP4849772B2 (en) * | 2001-09-27 | 2012-01-11 | ガンガゲン インコーポレーティッド | Lysine-deficient bacteriophages with low immunogenicity |
EP1437936A4 (en) | 2001-09-27 | 2005-10-12 | Pioneer Hi Bred Int | Phytate polynucleotides and methods of use |
US7393696B2 (en) * | 2001-09-28 | 2008-07-01 | Aspenbio Pharma, Inc. | Bovine pregnancy test |
US20030110518A1 (en) * | 2001-09-28 | 2003-06-12 | Houseknecht Karen L. | Melanocortin-5 receptor sequences and uses thereof |
DE60232742D1 (en) | 2001-10-04 | 2009-08-06 | Immunex Corp | UL16 BINDING PROTEIN 4 |
BR0213185A (en) | 2001-10-10 | 2004-09-14 | Sugen Inc | 3- [4- (Substituted Heterocyclyl) -pyrrol-2-ylmethylidene] 2-indolinone derivatives as kinase inhibitors |
MX339524B (en) | 2001-10-11 | 2016-05-30 | Wyeth Corp | Novel immunogenic compositions for the prevention and treatment of meningococcal disease. |
DE10151511A1 (en) | 2001-10-18 | 2003-05-08 | Basf Lynx Bioscience Ag | ee3 protein family and underlying DNA sequences |
EP1440091A1 (en) * | 2001-10-22 | 2004-07-28 | Novartis AG | Nogo receptor homologues and their use |
GB0126378D0 (en) | 2001-11-02 | 2002-01-02 | Oxford Biomedica Ltd | Antigen |
US20040067512A1 (en) * | 2001-11-09 | 2004-04-08 | Neurogenetics, Inc. | Single nucleotide polymorphisms and mutations on Alpha-2-Macroglobulin |
WO2003039600A1 (en) * | 2001-11-09 | 2003-05-15 | Neopharm, Inc. | Selective treatment of il-13 expressing tumors |
US20030162202A1 (en) * | 2001-11-09 | 2003-08-28 | Becker Kenneth David | Single nucleotide polymorphisms and mutations on Alpha-2-Macroglobulin |
WO2003044161A2 (en) * | 2001-11-15 | 2003-05-30 | Tularik Inc. | Gene amplification and overexpression in cancer |
US20030099621A1 (en) | 2001-11-29 | 2003-05-29 | Robert Chow | Stem cell screening and transplantation therapy for HIV infection |
CA2469306A1 (en) | 2001-12-05 | 2003-06-19 | Baylor College Of Medicine | Methods and compositions for control of bone formation via modulation of sympathetic tone |
PT1458888E (en) * | 2001-12-10 | 2011-06-01 | Novartis Ag | Methods of treating psychosis and schizophrenia based on polymorphisms in the cntf gene |
AU2002359697A1 (en) * | 2001-12-20 | 2003-07-09 | Tularik Inc. | Identification of an amplified gene and target for drug intervention |
US20060024292A1 (en) * | 2001-12-27 | 2006-02-02 | Gerngross Tillman U | Immunoglobulins comprising predominantly a Gal2GlcNAc2Man3GlcNAc2 glycoform |
US20060034829A1 (en) * | 2001-12-27 | 2006-02-16 | Gerngross Tillman U | Immunoglobulins comprising predominantly a MAN3GLCNAC2 glycoform |
US20040137440A1 (en) * | 2002-01-15 | 2004-07-15 | Biaoyang Lin | Androgen regulated nucleic acid molecules and encoded proteins |
US7462491B2 (en) * | 2002-01-31 | 2008-12-09 | Baylor College Of Medicine | Methods and compositions for diagnosis and monitoring of prostate cancer progression by detection of serum caveolin |
US7704700B2 (en) * | 2002-02-12 | 2010-04-27 | Burnham Institute For Medical Research | Methods for determining the prognosis for patients with a prostate neoplastic condition using inhibitor of apoptosis polypeptides |
ATE524739T1 (en) | 2002-02-13 | 2011-09-15 | American Diagnostica Inc | METHOD FOR SELECTING TREATMENT SCHEMES AND PREDICTING TREATMENT RESULTS IN CANCER PATIENTS |
WO2003072710A2 (en) * | 2002-02-21 | 2003-09-04 | Eastern Virginia Medical School | Protein biomarkers that distinguish prostate cancer from non-malignant cells |
JP2005535290A (en) | 2002-02-22 | 2005-11-24 | ジェネンテック・インコーポレーテッド | Compositions and methods for the treatment of immune related diseases |
US7662924B2 (en) * | 2002-02-22 | 2010-02-16 | The Board Of Trustees Of The University Of Illinois | Beta chain-associated regulator of apoptosis |
US20040025194A1 (en) * | 2002-02-22 | 2004-02-05 | Board Of Trustees Of The University Of Illinois | Beta chain-associated regulator of apoptosis |
US7294471B2 (en) * | 2002-02-27 | 2007-11-13 | Cskeys, Llc | Method for purifying cancer-specific proliferating cell nuclear antigen |
US7494655B2 (en) | 2002-03-05 | 2009-02-24 | Ramot At Tel-Aviv University Ltd. | Immunizing composition and method for inducing an immune response against the β-secretase cleavage site of amyloid precursor protein |
WO2003079025A2 (en) | 2002-03-19 | 2003-09-25 | Novartis Ag | Methods for the identification of compounds useful for the suppression of chronic neuropathic pain and compositions thereof |
WO2003079982A2 (en) * | 2002-03-19 | 2003-10-02 | Tularik Inc. | Gene amplification in cancer |
AU2003221841A1 (en) | 2002-04-03 | 2003-10-27 | Celltech R And D, Inc. | Association of polymorphisms in the sost gene region with bone mineral density |
WO2003094841A2 (en) * | 2002-05-06 | 2003-11-20 | Functional Genetics, Inc. | Mammalian genes involed in rapamycin resistance and tumorgenesis: annexin xiii genes |
WO2004040398A2 (en) * | 2002-05-06 | 2004-05-13 | Dana-Farber Cancer Institute, Inc. | Use of a computer to design a molecule |
US20040005615A1 (en) * | 2002-05-24 | 2004-01-08 | Jing Li | Amplification and overexpression of oncogenes |
EP2305710A3 (en) | 2002-06-03 | 2013-05-29 | Genentech, Inc. | Synthetic antibody phage libraries |
GB0213745D0 (en) | 2002-06-14 | 2002-07-24 | Univ Edinburgh | Enzyme |
WO2004004649A2 (en) | 2002-07-08 | 2004-01-15 | Genentech, Inc. | Compositions and methods for the treatment of immune related diseases |
US20040219609A1 (en) * | 2002-07-12 | 2004-11-04 | Day Anthony G. | Methods for modulating proteins not previously known as proteases |
WO2004007692A2 (en) * | 2002-07-17 | 2004-01-22 | U.S.Genomics, Inc. | Methods and compositions for analyzing polymers using chimeric tags |
ATE541047T1 (en) | 2002-08-01 | 2012-01-15 | Univ California | THERAPEUTIC MONOCLONAL ANTIBODIES FOR NEUTRALIZING BOTULINUM NEUROTOXINS |
AU2003254064A1 (en) * | 2002-08-07 | 2004-02-25 | Tularik Inc. | Amplification and overexpression of oncogenes |
CN1697972B (en) | 2002-08-13 | 2010-09-29 | N-Dia公司 | Devices and methods for detecting amniotic fluid in vaginal secretions |
US20060099676A1 (en) * | 2002-08-15 | 2006-05-11 | Limin Li | Mammalian genes involved in rapamycin resistance and tumorgenesis: rapr6 genes |
WO2004020581A2 (en) * | 2002-08-15 | 2004-03-11 | Functional Genetics, Inc. | Mammalian genes involved in rapamycin resistance and tumorgenesis: rapr7 genes |
AU2003256912A1 (en) | 2002-08-16 | 2004-03-03 | Yeda Research And Development Co. Ltd. | Tumor associated antigen, peptides thereof, and use of same as anti-tumor vaccines |
CA2745569C (en) | 2002-08-23 | 2015-07-14 | Bayer Schering Pharma Aktiengesellschaft | Biomarkers for diagnosing alzheimer`s disease |
US7785608B2 (en) * | 2002-08-30 | 2010-08-31 | Wyeth Holdings Corporation | Immunogenic compositions for the prevention and treatment of meningococcal disease |
US20040115194A1 (en) | 2002-09-06 | 2004-06-17 | Yi Wang | Method of treatment of asthma using antibodies to complement component C5 |
WO2004024068A2 (en) | 2002-09-11 | 2004-03-25 | Genentech, Inc. | Novel composition and methods for the treatment of immune related diseases |
EP1562587A4 (en) | 2002-09-11 | 2006-07-19 | Genentech Inc | Novel compositions and methods for the treatment of immune related diseases |
WO2004024072A2 (en) | 2002-09-11 | 2004-03-25 | Genentech, Inc. | Novel compositions and methods for the treatment of immune related diseases |
JP2006515165A (en) | 2002-09-16 | 2006-05-25 | ジェネンテック・インコーポレーテッド | Novel compositions and methods for the treatment of immune related diseases |
US7094551B2 (en) * | 2002-09-17 | 2006-08-22 | Zahradnik Richard J | Immunoassays, assay methods, antibodies and method of creating antibodies for detecting FGF-23 |
WO2004028479A2 (en) | 2002-09-25 | 2004-04-08 | Genentech, Inc. | Nouvelles compositions et methodes de traitement du psoriasis |
CA2498854A1 (en) * | 2002-10-02 | 2004-04-15 | Harald Kropshofer | Novel mhc ii associated peptides |
US7432351B1 (en) | 2002-10-04 | 2008-10-07 | Mayo Foundation For Medical Education And Research | B7-H1 variants |
CA2501330A1 (en) * | 2002-10-11 | 2004-04-22 | Sentina Biotechnology Incorporated | Methods for detection of breast cancer |
US20080293750A1 (en) * | 2002-10-17 | 2008-11-27 | Anna Helgadottir | Susceptibility Gene for Myocardial Infarction, Stroke, Paod and Methods of Treatment |
JP3447009B1 (en) * | 2002-10-29 | 2003-09-16 | 實 平垣 | Construct structure and method for producing the same |
JP2006517785A (en) | 2002-10-29 | 2006-08-03 | ジェネンテック・インコーポレーテッド | Novel compositions and methods for the treatment of immune related diseases |
EP1563100B1 (en) | 2002-11-01 | 2013-04-24 | Iris Molecular Diagnostics, Inc. | Displacement sandwich immuno-pcr |
AU2003295401B2 (en) | 2002-11-08 | 2010-04-29 | Genentech, Inc. | Compositions and methods for the treatment of natural killer cell related diseases |
US20050129711A1 (en) | 2002-11-14 | 2005-06-16 | Janakiraman Ramachandran | Incapacitated whole-cell immunogenic bacterial compositions produced by recombinant expression |
WO2004046330A2 (en) | 2002-11-15 | 2004-06-03 | Morphotek, Inc. | Methods of generating high-production of antibodies from hybridomas created by in vitro immunization |
WO2004047728A2 (en) | 2002-11-26 | 2004-06-10 | Genentech, Inc. | Compositions and methods for the treatment of immune related diseases |
US20040101860A1 (en) * | 2002-11-27 | 2004-05-27 | Jones Alison M. | Predicting animal performance |
US20040259226A1 (en) * | 2003-05-30 | 2004-12-23 | Robey W. Wade | Monitoring for and detecting microbes used in bioterrorism |
US7256327B2 (en) * | 2002-11-29 | 2007-08-14 | The University Of Hong Kong | Genetically modified plants expressing proteinase inhibitors, SaPIN2a or SaPIN2b, and methods of use thereof for the inhibition of trypsin- and chymotrypsin-like activities |
AU2003283217A1 (en) * | 2002-12-03 | 2004-06-23 | Aarhus Amt | Method for determing predisposition to manifestation of immune system related diseases |
AU2003285724A1 (en) * | 2002-12-31 | 2004-07-22 | Pharmacia & Upjohn Company Llc | Canine l-pbe sequences |
AU2003288649A1 (en) * | 2002-12-31 | 2004-07-22 | Pharmacia & Upjohn Company Llc | Canine cyp1a2 sequences |
WO2004057940A2 (en) * | 2002-12-31 | 2004-07-15 | Pharmacia & Upjohn Company Llc | Canine dioxin/aryl hydrocarbon receptor sequences |
US7560272B2 (en) * | 2003-01-04 | 2009-07-14 | Inverness Medical Switzerland Gmbh | Specimen collection and assay container |
EP1585815A4 (en) * | 2003-01-21 | 2006-02-22 | Bristol Myers Squibb Co | Polynucleotide encoding a novel acyl coenzyme a, monoacylglycerol acyltransferase-3 (mgat3), and uses thereof |
US7449321B2 (en) * | 2003-01-22 | 2008-11-11 | National University Of Singapore | Molecules, compositions, methods and kits for applications associated with flaviviruses |
AU2004209638B2 (en) | 2003-02-01 | 2011-02-03 | Tanox, Inc. | High affinity anti-human IgE antibodies |
US7335359B2 (en) | 2003-02-06 | 2008-02-26 | Tripep Ab | Glycosylated specificity exchangers |
WO2004069873A2 (en) * | 2003-02-06 | 2004-08-19 | Tripep Ab | Antigen/antibody or ligand/receptor glycosylated specificity exchangers |
WO2004071462A2 (en) * | 2003-02-12 | 2004-08-26 | Johns Hopkins University | Methods and compositions for treatment of viral infections based on tsg101-vps28 interaction |
US7157551B2 (en) * | 2003-02-14 | 2007-01-02 | Cephalon, Inc. | Compositions and methods for the detection and treatment of methylthioadenosine phosphorylase deficient cancers |
GB0304515D0 (en) * | 2003-02-27 | 2003-04-02 | Dakocytomation Denmark As | Standard |
US20040178714A1 (en) * | 2003-03-11 | 2004-09-16 | Pan Wun Fang | Decorative bulb of a series connected light string |
US20040185446A1 (en) * | 2003-03-18 | 2004-09-23 | Jones Alison M. | Cpn60 targets for quantification of microbial species |
US20040185434A1 (en) * | 2003-03-21 | 2004-09-23 | Robey W. Wade | Detecting microbial contamination in animal by-products |
US20040185454A1 (en) * | 2003-03-21 | 2004-09-23 | Jones Alison M. | Identification and quantification of microbial species in a sample |
WO2004087758A2 (en) * | 2003-03-26 | 2004-10-14 | Neopharm, Inc. | Il 13 receptor alpha 2 antibody and methods of use |
DK2360475T3 (en) * | 2003-03-27 | 2020-01-06 | Childrens Hospital Med Ct | Method and kit for detecting early onset of renal tubular cell damage |
JP2006525330A (en) * | 2003-04-16 | 2006-11-09 | ワイエス・ホールディングス・コーポレーション | Novel immunogenic composition for prevention and treatment of meningococcal disease |
US7321065B2 (en) * | 2003-04-18 | 2008-01-22 | The Regents Of The University Of California | Thyronamine derivatives and analogs and methods of use thereof |
US20060263813A1 (en) * | 2005-05-11 | 2006-11-23 | Expression Diagnostics, Inc. | Methods of monitoring functional status of transplants using gene panels |
US7892745B2 (en) * | 2003-04-24 | 2011-02-22 | Xdx, Inc. | Methods and compositions for diagnosing and monitoring transplant rejection |
US20070248978A1 (en) * | 2006-04-07 | 2007-10-25 | Expression Diagnostics, Inc. | Steroid responsive nucleic acid expression and prediction of disease activity |
KR100531760B1 (en) * | 2003-04-28 | 2005-11-29 | 대한민국(관리부서 : 농림부 국립수의과학검역원) | Method of Diagnosis of Foot and Mouth Disease and The Diagnotic kit |
US7892563B2 (en) * | 2003-05-20 | 2011-02-22 | Wyeth Holdings Corporation | Methods for treatment of severe acute respiratory syndrome (SARS) |
US20040241662A1 (en) * | 2003-05-30 | 2004-12-02 | Robey W. Wade | Detecting microbial contamination in grain and related products |
US20050250094A1 (en) * | 2003-05-30 | 2005-11-10 | Nanosphere, Inc. | Method for detecting analytes based on evanescent illumination and scatter-based detection of nanoparticle probe complexes |
EP1629014A2 (en) * | 2003-05-30 | 2006-03-01 | Genentech, Inc. | Polypeptides that bind an anti-tissue factor antibody and uses thereof |
US7405274B2 (en) | 2003-06-04 | 2008-07-29 | Fibrogen, Inc. | Connective tissue growth factor antibodies |
WO2004110384A2 (en) * | 2003-06-12 | 2004-12-23 | Vaxgen, Inc. | Hiv-1 envelope glycoproteins having unusual disulfide structure |
EP1636270B1 (en) | 2003-06-16 | 2016-07-20 | UCB Pharma S.A. | Antibodies specific for sclerostin and methods for increasing bone mineralization |
IL156495A0 (en) * | 2003-06-17 | 2004-01-04 | Prochon Biotech Ltd | Use of fgfr3 antagonists for treating t cell mediated diseases |
JP4750024B2 (en) | 2003-06-20 | 2011-08-17 | プロテイン サイエンシーズ コーポレイション | Vectors expressing SARS immunogens, compositions containing such vectors or expression products thereof, and methods and assays for their production and use |
US20050026194A1 (en) * | 2003-06-20 | 2005-02-03 | Tularik Inc. | Gene amplification and overexpression in cancer |
GB0315991D0 (en) * | 2003-07-08 | 2003-08-13 | Dakocytomation Denmark As | Standard |
KR100945327B1 (en) | 2003-07-08 | 2010-03-08 | 제넨테크, 인크. | Il-17a/f heterologous polypeptides and therapeutic uses thereof |
US20050014734A1 (en) * | 2003-07-18 | 2005-01-20 | Genovate Biotechnology Co., Ltd. | Modulation of interleukin-10 by DHEA |
ATE554108T1 (en) | 2003-07-25 | 2012-05-15 | Amgen Inc | PROCEDURES REGARDING LDCAM AND CRTAM |
EP1649028B1 (en) * | 2003-07-25 | 2012-08-22 | Genvec, Inc. | Adenoviral vector-based vaccines |
GB0317592D0 (en) * | 2003-07-26 | 2003-08-27 | Astrazeneca Ab | Method |
US20050106667A1 (en) | 2003-08-01 | 2005-05-19 | Genentech, Inc | Binding polypeptides with restricted diversity sequences |
NZ619746A (en) | 2003-08-06 | 2014-05-30 | Senomyx Inc | Novel flavors, flavor modifiers, tastants, taste enhancers, umami or sweet tastants, and/or enhancers and use thereof |
WO2005019258A2 (en) | 2003-08-11 | 2005-03-03 | Genentech, Inc. | Compositions and methods for the treatment of immune related diseases |
US20080233119A2 (en) | 2003-08-20 | 2008-09-25 | University Of Miami | Compositions and methods for treating inflammatory lung disease |
US20050048589A1 (en) * | 2003-08-25 | 2005-03-03 | Moncef Jendoubi | Lung cancer specific gene products: their coding sequence, their antibodies and their use in diagnostic, therapeutic and disease management of lung cancer |
US7517495B2 (en) * | 2003-08-25 | 2009-04-14 | Inverness Medical Switzerland Gmbh | Biological specimen collection and analysis system |
DK1663281T3 (en) | 2003-08-29 | 2014-03-17 | Dyax Corp | POLY-PEGYLED PROTEASE INHIBITORS |
US7604994B2 (en) * | 2003-09-03 | 2009-10-20 | Morphotek, Inc. | Genetically altered antibody-producing cell lines with improved antibody characteristics |
AU2004270721A1 (en) * | 2003-09-05 | 2005-03-17 | The Scripps Research Institute | Detection of cholesterol ozonation products |
EP1680518A2 (en) * | 2003-09-19 | 2006-07-19 | Decode Genetics EHF. | Inversion on chromosome 8p23 is a risk factor for anxiety disorders, depression and bipolar |
US20050214279A1 (en) * | 2003-09-19 | 2005-09-29 | Silverstein Samuel C | Methods for stimulating human leukocytes to kill bacteria, yeast and fungi in biofilms that have formed in/on prosthetic devices, catheters, tissues and organs in vivo |
US20050069958A1 (en) * | 2003-09-26 | 2005-03-31 | Mills Rhonda A. | Method for simultaneous evaluation of a sample containing a cellular target and a soluble analyte |
US20050069546A1 (en) | 2003-09-30 | 2005-03-31 | Yaron Ilan | Educated NKT cells and their uses in the treatment of immune-related disorders |
IL158287A0 (en) | 2003-10-07 | 2004-05-12 | Yeda Res & Dev | Antibodies to nik, their preparation and use |
EP2339024B1 (en) | 2003-10-21 | 2014-12-31 | Orion Genomics, LLC | Methods for quantitative determination of methylation density in a DNA locus |
ES2343965T3 (en) | 2003-11-25 | 2010-08-13 | The Government Of The United States, As Represented By The Secretary Of Health And Human Services | ANTI-CD22 ANTIBODIES AND MUTED IMMUNOCONGUJADOS. |
US20050118727A1 (en) * | 2003-12-01 | 2005-06-02 | Carsten Schelp | Conjugates and their use in detection methods |
WO2005062048A1 (en) * | 2003-12-01 | 2005-07-07 | Dade Behring Marburg Gmbh | Homogeneous detection method |
CA2550900A1 (en) | 2003-12-23 | 2005-07-07 | Mount Sinai Hospital | Methods for detecting markers associated with endometrial disease or phase |
PL1703893T3 (en) | 2003-12-23 | 2012-09-28 | Genentech Inc | Novel anti-il 13 antibodies and uses thereof |
US7150995B2 (en) * | 2004-01-16 | 2006-12-19 | Metrika, Inc. | Methods and systems for point of care bodily fluid analysis |
WO2005071058A2 (en) * | 2004-01-27 | 2005-08-04 | Compugen Ltd. | Methods and systems for annotating biomolecular sequences |
US20100216863A1 (en) * | 2004-01-30 | 2010-08-26 | Decode Genetics Ehf. | Susceptibility Gene for Myocardial Infarction, Stroke, and PAOD; Methods of Treatment |
US8158362B2 (en) * | 2005-03-30 | 2012-04-17 | Decode Genetics Ehf. | Methods of diagnosing susceptibility to myocardial infarction and screening for an LTA4H haplotype |
AU2005215017A1 (en) * | 2004-02-17 | 2005-09-01 | Cancervax Corporation | Method and composition for angiogenesis inhibition |
AU2005214382B2 (en) | 2004-02-19 | 2011-08-04 | Genentech, Inc. | CDR-repaired antibodies |
US7604956B2 (en) * | 2004-03-01 | 2009-10-20 | Biotraces, Inc. | Supersensitive immunoassays |
US7943334B2 (en) * | 2004-03-05 | 2011-05-17 | Prima Meat Packers, Ltd. | Method of detecting allergen |
US20050227370A1 (en) * | 2004-03-08 | 2005-10-13 | Ramel Urs A | Body fluid analyte meter & cartridge system for performing combined general chemical and specific binding assays |
ES2609395T5 (en) | 2004-03-12 | 2021-08-06 | Intercept Pharmaceuticals Inc | Fibrosis treatment using Fxr ligands |
US20050221408A1 (en) * | 2004-03-19 | 2005-10-06 | U.S. Genomics, Inc. | Compositions and methods for detection of single molecules |
US7794713B2 (en) * | 2004-04-07 | 2010-09-14 | Lpath, Inc. | Compositions and methods for the treatment and prevention of hyperproliferative diseases |
EP2207033B1 (en) | 2004-04-15 | 2014-06-18 | University of Florida Research Foundation, Inc. | Neural proteins as biomarkers for nervous system injury and other neural disorders |
BRPI0509419A (en) * | 2004-04-16 | 2007-09-04 | Genentech Inc | enzyme-linked immunosorbent assay method, antibodies, hybridoma and immunoassay kit |
WO2005115394A2 (en) * | 2004-04-20 | 2005-12-08 | New York University School Of Medicine | Prenyl-electrostatic switch, and methods of use |
CA2564769C (en) | 2004-04-23 | 2013-12-17 | Pharmacia & Upjohn Company Llc | Cellular permissivity factor for viruses, and uses thereof |
ES2389047T3 (en) | 2004-04-29 | 2012-10-22 | Otsuka Pharmaceutical Co., Ltd. | Specific antibodies against glycoprotein VI and production procedures for these antibodies |
EP1753449A4 (en) * | 2004-04-30 | 2009-09-23 | Corthera Inc | Methods and compositions for control of fetal growth via modulation of relaxin |
US20050272101A1 (en) * | 2004-06-07 | 2005-12-08 | Prasad Devarajan | Method for the early detection of renal injury |
US7939251B2 (en) | 2004-05-06 | 2011-05-10 | Roche Molecular Systems, Inc. | SENP1 as a marker for cancer |
MY148646A (en) | 2004-05-10 | 2013-05-15 | Abgenomics Cooperatief Ua | Anti-psgl-1 antibodies |
TWI454274B (en) | 2004-05-11 | 2014-10-01 | Abgenomics Cooperatief Ua | T-cell death-inducing epitopes |
AU2005246289A1 (en) * | 2004-05-15 | 2005-12-01 | Genentech, Inc. | Cross-screening system and methods for detecting a molecule having binding affinity for a target molecule |
US7504205B2 (en) * | 2004-05-17 | 2009-03-17 | The Burnham Institute | Uncharacterized ORF3 in SARS-coronavirus is a cyclic-AMP-dependent kinase and a target for SARS therapy |
US7604947B2 (en) * | 2004-06-09 | 2009-10-20 | Cornell Research Foundation, Inc. | Detection and modulation of cancer stem cells |
US20060040876A1 (en) | 2004-06-10 | 2006-02-23 | Rong-Hwa Lin | Modulation of peroxisome proliferator-activated receptors |
EP1766077B1 (en) | 2004-06-21 | 2012-03-28 | The Board Of Trustees Of The Leland Stanford Junior University | Genes and pathways differentially expressed in bipolar disorder and/or major depressive disorder |
US8034553B2 (en) | 2004-06-24 | 2011-10-11 | Kimberly-Clark Worldwide, Inc. | Biomarkers for wound healing |
US7973134B2 (en) * | 2004-07-07 | 2011-07-05 | Cell Signaling Technology, Inc. | Reagents for the detection of protein phosphorylation in anaplastic large cell lymphoma signaling pathways |
EP2287310B1 (en) | 2004-07-22 | 2015-05-06 | Five Prime Therapeutics, Inc. | Compositions and methods using MGD-CSF in disease treatment |
US7342093B2 (en) | 2004-07-23 | 2008-03-11 | University Of Massachusetts | Compounds that inhibit Hsp90 protein-protein interactions with IAP proteins |
US20060024744A1 (en) * | 2004-07-28 | 2006-02-02 | Mills Rhonda A | Methods for substantially simultaneous evaluation of a sample containing a cellular target and a soluble analyte |
US7510858B2 (en) * | 2004-08-02 | 2009-03-31 | Janssen Pharmaceutica N.V. | IRAK 1c splice variant and its use |
US7598080B2 (en) | 2004-08-20 | 2009-10-06 | Carl Deirmengian | Diagnostic assay for source of inflammation |
US7893197B2 (en) * | 2004-08-25 | 2011-02-22 | Janssen Pharmaceutica N.V. | Relaxin-3 chimeric polypeptides and their preparation and use |
WO2006039045A2 (en) * | 2004-09-01 | 2006-04-13 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Adenoviral vectors able to transduce apcs, potential use in immune response generation |
US7645575B2 (en) * | 2004-09-08 | 2010-01-12 | Xdx, Inc. | Genes useful for diagnosing and monitoring inflammation related disorders |
FI20041204A0 (en) | 2004-09-16 | 2004-09-16 | Riikka Lund | Methods for the utilization of new target genes associated with immune-mediated diseases |
GB0421639D0 (en) | 2004-09-29 | 2004-10-27 | Proteome Sciences Plc | Methods and compositions relating to alzheimer's disease |
US7935790B2 (en) * | 2004-10-04 | 2011-05-03 | Cell Singaling Technology, Inc. | Reagents for the detection of protein phosphorylation in T-cell receptor signaling pathways |
WO2006042002A2 (en) * | 2004-10-05 | 2006-04-20 | Oregon Health And Science University | Compositions and methods for treating disease |
CA2943949C (en) * | 2004-10-06 | 2020-03-31 | Mayo Foundation For Medical Education And Research | B7-h1 and methods of diagnosis, prognosis, and treatment of cancer |
US8969291B2 (en) | 2004-10-08 | 2015-03-03 | Enzo Therapeutics, Inc. | Methods for decreasing leptin levels or activity for treating inflammation |
WO2006047417A2 (en) | 2004-10-21 | 2006-05-04 | University Of Florida Research Foundation, Inc. | Detection of cannabinoid receptor biomarkers and uses thereof |
US20080176790A1 (en) | 2004-10-29 | 2008-07-24 | Defrees Shawn | Remodeling and Glycopegylation of Fibroblast Growth Factor (Fgf) |
EP1842226B2 (en) * | 2004-11-03 | 2014-07-02 | Iris International, Inc. | Homogeneous analyte detection |
EP2302078B1 (en) | 2004-11-03 | 2015-07-15 | Iris Molecular Diagnostics, Inc. | Microbubbles for affinity concentration |
WO2006048877A2 (en) * | 2004-11-04 | 2006-05-11 | Fibron Limited | Treatment of b-cell malignancies with fgfr3 inhibitors |
AU2005307765C1 (en) | 2004-11-16 | 2012-07-05 | Trustees Of Boston University | Roles for Dual Endothelin-1/Angiotensin II Receptor (DEAR) in hypertension and angiogenesis |
US20070207496A1 (en) * | 2004-11-19 | 2007-09-06 | Larsen Oeistein | Diagnostic control system |
CN101291683B (en) | 2004-11-24 | 2011-08-17 | 纽普罗研究有限公司 | Methods and compositions for treating conditions |
US7608277B2 (en) | 2004-12-01 | 2009-10-27 | Gene Therapy Systems, Inc. | Tuberculosis nucleic acids, polypeptides and immunogenic compositions |
PL1831699T3 (en) * | 2004-12-20 | 2010-04-30 | Antibodyshop As | Determination of neutrophil gelatinase-associated lipocalin (ngal) as a diagnostic marker for renal disorders |
US7807789B2 (en) * | 2004-12-21 | 2010-10-05 | Cell Signaling Technology, Inc. | Reagents for the detection of protein phosphorylation in EGFR-signaling pathways |
SG176509A1 (en) | 2004-12-22 | 2011-12-29 | Genentech Inc | Methods for producing soluble multi-membrane-spanning proteins |
CA2531616A1 (en) * | 2004-12-28 | 2006-06-28 | Kabushiki Kaisha Kobe Seiko Sho (Kobe Steel, Ltd.) | High strength thin steel sheet having high hydrogen embrittlement resisting property and high workability |
US8697674B2 (en) | 2004-12-29 | 2014-04-15 | Naturon, Inc. | Xanthurenic acid derivative pharmaceutical compositions and methods related thereto |
EP1831366A2 (en) | 2004-12-30 | 2007-09-12 | Agency for Science, Technology and Research | Chinese hamster apoptosis-related genes |
EP2153848A3 (en) | 2005-01-27 | 2010-07-21 | The Regents of the University of California | Therapeutic monoclonal antibodies that neutralize botulinium neurotoxins |
DE602006002809D1 (en) * | 2005-02-16 | 2008-10-30 | Dana Farber Cancer Inst Inc | METHOD FOR DETECTING AN OVARIAN CARCINOMA |
WO2006095348A2 (en) * | 2005-03-10 | 2006-09-14 | Hadasit Medical Research Services & Development Ltd. | Antigen specific lymphocytes, compositions thereof, and methods for isolation and preparation thereof |
EP1863531A1 (en) | 2005-03-19 | 2007-12-12 | Medical Research Council | Improvements in or relating to treatment and prevention of viral infections |
US20070092886A1 (en) * | 2005-03-22 | 2007-04-26 | Raymond Tabibiazar | Methods and compositions for diagnosis, monitoring and development of therapeutics for treatment of atherosclerotic disease |
RS59399B1 (en) | 2005-03-23 | 2019-11-29 | Genmab As | Antibodies against cd38 for treatment of multiple myeloma |
US8323645B2 (en) | 2005-03-24 | 2012-12-04 | Millennium Pharmaceuticals, Inc. | Antibodies that bind OV064 and methods of use therefor |
US20070037232A1 (en) * | 2005-03-31 | 2007-02-15 | Barasch Jonathan M | Detection of NGAL in chronic renal disease |
CA2635198C (en) | 2005-04-01 | 2019-11-12 | University Of Florida Research Foundation, Inc | Biomarkers of liver injury |
US8048638B2 (en) * | 2005-04-01 | 2011-11-01 | University Of Florida Research Foundation, Inc. | Biomarkers of liver injury |
DK2645106T3 (en) | 2005-04-04 | 2017-10-02 | Biogen Ma Inc | Methods for Evaluating an Immune Response to a Therapeutic Agent |
US9187546B2 (en) | 2005-04-08 | 2015-11-17 | Novo Nordisk A/S | Compositions and methods for the preparation of protease resistant human growth hormone glycosylation mutants |
MX2007012547A (en) | 2005-04-11 | 2008-03-11 | Savient Pharmaceuticals Inc | Variant forms of urate oxidase and use thereof. |
US20090099340A1 (en) * | 2007-10-12 | 2009-04-16 | Cell Signaling Technology, Inc. | Reagents for the detection of protein phosphorylation in carcinoma signaling pathways |
EP1877775A4 (en) * | 2005-05-02 | 2009-06-24 | Univ Missouri | Detection of carbohydrate biomarkers |
US7592429B2 (en) * | 2005-05-03 | 2009-09-22 | Ucb Sa | Sclerostin-binding antibody |
US8003108B2 (en) * | 2005-05-03 | 2011-08-23 | Amgen Inc. | Sclerostin epitopes |
WO2006125021A2 (en) * | 2005-05-16 | 2006-11-23 | Dana Farber Cancer Institute, Inc. | Fibrinogen alpha and hemoglobin polypeptides as cancer markers |
NZ563913A (en) | 2005-05-18 | 2010-03-26 | Decode Genetics Ehf | Markers for prostate cancer in LD Block A on chromosome 8q24.21 |
AU2006321289B2 (en) * | 2005-05-23 | 2011-12-08 | Phadia Ab | Two step lateral flow assay methods and devices |
US7968697B2 (en) * | 2005-05-25 | 2011-06-28 | Chrontech Pharma Ab | Hepatitis C virus non-structural NS3/4A fusion gene |
SI1907000T2 (en) | 2005-06-08 | 2020-07-31 | Dana-Farber Cancer Institute | Methods and compositions for the treatment of persistent HIV infections by inhibiting the programmed cell death 1 (PD-1) pathway |
BRPI0612301A2 (en) * | 2005-06-20 | 2009-01-27 | Decode Genetics Ehf | method for diagnosing a susceptibility to type ii diabetes in an individual, kit, and, method for assessing an individual for the likelihood of response to a tcf7l2 therapeutic agent |
WO2007008604A2 (en) * | 2005-07-08 | 2007-01-18 | Bristol-Myers Squibb Company | Single nucleotide polymorphisms associated with dose-dependent edema and methods of use thereof |
US7906297B2 (en) | 2005-07-20 | 2011-03-15 | Cell Signaling Technology, Inc. | Reagents for the detection of phosphorylated ATR kinase (Ser 428) and uses thereof |
WO2007019541A2 (en) * | 2005-08-08 | 2007-02-15 | Onconon, Llc. | Antibody compositions, methods for treating neoplastic disease and methods for regulating fertility |
US20070202512A1 (en) * | 2005-08-19 | 2007-08-30 | Bristol-Myers Squibb Company | Human single nucleotide polymorphisms associated with dose-dependent weight gain and methods of use thereof |
US20070128184A1 (en) | 2005-08-30 | 2007-06-07 | Eckhard Podack | Immunomodulating tumor necrosis factor receptor 25 (TNFR25) agonists, antagonists and immunotoxins |
WO2007027906A2 (en) * | 2005-08-31 | 2007-03-08 | Cell Signaling Technology, Inc. | Reagents for the detection of protein phosphorylation in leukemia signaling pathways |
EP1929003A4 (en) | 2005-08-31 | 2009-04-29 | Cell Signaling Technology Inc | Reagents for the detection of protein phosphorylation in carcinoma signaling pathways |
US20100151495A9 (en) * | 2005-08-31 | 2010-06-17 | Cell Signaling Technolgy, Inc. | Reagents for the detection of protein phosphorylation in carcinoma signaling pathways |
US8193328B2 (en) * | 2005-09-08 | 2012-06-05 | Philadelphia Health & Education Corporation | Identification of modulators of serine protease inhibitor Kazal and their use as anti-cancer and anti-viral agents |
AU2005336263A1 (en) * | 2005-09-09 | 2007-03-15 | Glycofi, Inc. | Immunoglobulin comprising predominantly a man7GlcNAc2, Man8GlcNAc2 glycoform |
US7611834B2 (en) * | 2005-09-30 | 2009-11-03 | Sandia Corporation | Methods and devices for protein assays |
IL172297A (en) | 2005-10-03 | 2016-03-31 | Compugen Ltd | Soluble vegfr-1 variants for diagnosis of preeclamsia |
AU2006302031A1 (en) | 2005-10-11 | 2007-04-19 | Tethys Bioscience, Inc. | Diabetes-associated markers and methods of use thereof |
US8119358B2 (en) | 2005-10-11 | 2012-02-21 | Tethys Bioscience, Inc. | Diabetes-related biomarkers and methods of use thereof |
US20080090304A1 (en) * | 2006-10-13 | 2008-04-17 | Barasch Jonathan Matthew | Diagnosis and monitoring of chronic renal disease using ngal |
US20080213274A1 (en) * | 2005-10-28 | 2008-09-04 | Sabbadini Roger A | Compositions and methods for the treatment and prevention of fibrotic, inflammatory, and neovascularization conditions of the eye |
US20090074720A1 (en) * | 2005-10-28 | 2009-03-19 | Sabbadini Roger A | Methods for decreasing immune response and treating immune conditions |
US20090155850A1 (en) * | 2005-10-28 | 2009-06-18 | The Florida International University Board Of Trustees | Horse:Human Chimeric Antibodies |
EP1948687A2 (en) * | 2005-10-31 | 2008-07-30 | Janssen Pharmaceutica N.V. | A polypeptide complex of trpm8 and calmodulin and its uses thereof |
EP2395012B8 (en) | 2005-11-02 | 2018-06-06 | Arbutus Biopharma Corporation | Modified siRNA molecules and uses thereof |
UA99591C2 (en) | 2005-11-04 | 2012-09-10 | Дженентек, Инк. | Use of complement pathway inhibitors to treat ocular diseases |
CA2628238A1 (en) | 2005-11-07 | 2007-05-18 | The Scripps Research Institute | Compositions and methods for controlling tissue factor signaling specificity |
US20070161089A1 (en) * | 2005-11-08 | 2007-07-12 | Genentech, Inc. | Method of Producing Pan-Specific Antibodies |
UA96139C2 (en) | 2005-11-08 | 2011-10-10 | Дженентек, Інк. | Anti-neuropilin-1 (nrp1) antibody |
EP2564864B8 (en) | 2005-11-12 | 2015-05-13 | The Board of Trustees of The Leland Stanford Junior University | FGF2-related methods for diagnosing and treating depression |
EP1952147A2 (en) | 2005-11-16 | 2008-08-06 | Novartis AG | Biomarkers for anti-nogo-a antibody treatment in spinal cord injury |
CN101360826B (en) | 2005-11-18 | 2014-04-30 | 格兰马克药品股份有限公司 | Anti-alpha2 integrin antibodies and their uses |
ES2409835T3 (en) | 2005-11-28 | 2013-06-28 | Zymogenetics, Inc. | IL-21 antagonists |
CA3046754A1 (en) | 2005-11-29 | 2007-06-07 | Cambridge Enterprise Limited | Markers for breast cancer including refsnp_id 3817198 |
US7822474B2 (en) * | 2005-11-30 | 2010-10-26 | Cedars-Sinai Medical Center | Methods for the prediction of arrhythmias and prevention of sudden cardiac death |
KR101453570B1 (en) | 2005-12-02 | 2014-10-22 | 제넨테크, 인크. | Compositions and methods for the treatment of diseases and disorders associated with cytokine signaling involving antibodies that bind to il-22 and il-22r |
US20070134814A1 (en) * | 2005-12-09 | 2007-06-14 | Kajander E O | Methods and compositions for the detection of calcifying nano-particles, identification and quantification of associated proteins thereon, and correlation to disease |
CA2634797A1 (en) | 2005-12-22 | 2007-07-05 | Abbott Laboratories | Methods and marker combinations for screening for predisposition to lung cancer |
US9347945B2 (en) | 2005-12-22 | 2016-05-24 | Abbott Molecular Inc. | Methods and marker combinations for screening for predisposition to lung cancer |
US20090215084A1 (en) * | 2006-01-05 | 2009-08-27 | Mayo Foundation For Medical Education And Research | B7-h1 and b7-h4 in cancer |
WO2007082144A2 (en) * | 2006-01-05 | 2007-07-19 | Mayo Foundation For Medical Education And Research | B7-h1 and survivin in cancer |
RU2520088C2 (en) | 2006-01-12 | 2014-06-20 | Алексион Фармасьютикалз, Инк. | Antibodies to ox-2/cd200 and their application |
WO2007084397A2 (en) * | 2006-01-12 | 2007-07-26 | Janssen Pharmaceutica N.V. | Processing of slpi by chymase |
CA2637267A1 (en) | 2006-01-16 | 2007-07-19 | Compugen Ltd. | Novel nucleotide and amino acid sequences, and methods of use thereof for diagnosis |
US20120208824A1 (en) | 2006-01-20 | 2012-08-16 | Cell Signaling Technology, Inc. | ROS Kinase in Lung Cancer |
EP3360965A1 (en) | 2006-01-20 | 2018-08-15 | Cell Signaling Technology, Inc. | Translocation and mutant ros kinase in human non-small cell lung carcinoma |
CA2642984A1 (en) * | 2006-02-22 | 2007-09-07 | The Texas A & M University System | Antibodies recognizing a highly expressed putative antigen of ca-mrsa and methods of use |
EP1991246B1 (en) | 2006-02-22 | 2013-09-11 | Zhenglun Zhu | Treatment of development-related disorders |
DK2676967T3 (en) | 2006-02-28 | 2019-09-16 | Biogen Ma Inc | Methods for treating inflammatory and autoimmune diseases with natalizumab |
MX2008011176A (en) | 2006-03-03 | 2008-09-10 | Elan Pharm Inc | Methods of treating inflammatory and autoimmune diseases with natalizumab. |
US8293500B2 (en) | 2006-03-22 | 2012-10-23 | Viral Logic Systems Technology Corp. | Methods for identifying polypeptide targets and uses thereof for treating immunological diseases |
US8129334B2 (en) | 2006-03-31 | 2012-03-06 | The Regents Of The University Of California | Methods and compositions for treating neurodegenerative disorders and Alzheimer'S disease and improving normal memory |
BRPI0709481A2 (en) * | 2006-04-07 | 2011-07-19 | Government Of The Us Secretary Dept Of Health And Human Services | isolated monoclonal antibody, isolated human monoclonal antibody, pharmaceutical composition, isolated recombinant anti-igf-i and anti-igf-ii antibody or antigen-binding fragment thereof, method for detecting factor i and factor ii of human insulin growth in a sample , method for detecting human insulin growth factor i in a sample, isolated nucleic acid, recombinant cell, host cell, method for preparing an antibody, method for preparing an antibody, method for treating neoplastic disease in a mammalian individual, method for to diagnose neoplastic disease in a mammal and method to classify a drug candidate compound |
PL2013225T3 (en) * | 2006-04-12 | 2015-06-30 | Crealta Pharmaceuticals Llc | Purification of proteins with cationic surfactant |
EP2447360A1 (en) | 2006-04-14 | 2012-05-02 | Cell Signaling Technology, Inc. | Gene defects and mutant ALK kinase in human solid tumors |
WO2007124361A2 (en) * | 2006-04-20 | 2007-11-01 | Mayo Foundation For Medical Education And Research | Soluble b7-h1 |
ES2640453T3 (en) | 2006-04-21 | 2017-11-03 | Senomyx, Inc. | Processes for preparing solid flavoring compositions |
WO2007127335A2 (en) * | 2006-04-27 | 2007-11-08 | Cell Signaling Technology, Inc. | Reagents for the detection of protein phosphorylation in atm and atr kinase signaling pathways |
EP2016097A2 (en) | 2006-05-04 | 2009-01-21 | Genentech, Inc. | Methods and compositions relating to zpa polypeptides |
US8790871B2 (en) * | 2006-05-09 | 2014-07-29 | Musc Foundation For Research Development | Detecting diastolic heart failure by protease and protease inhibitor plasma profiling |
JP2009537145A (en) * | 2006-05-15 | 2009-10-29 | バイラル ロジック システムズ テクノロジー コーポレーション | Compositions and methods associated with CD47 for treating immunological diseases and disorders |
US8377448B2 (en) * | 2006-05-15 | 2013-02-19 | The Board Of Trustees Of The Leland Standford Junior University | CD47 related compositions and methods for treating immunological diseases and disorders |
US7745584B2 (en) * | 2006-05-22 | 2010-06-29 | California Institute Of Technology | Antibodies to sulfated carbohydrates |
US20100196336A1 (en) | 2006-05-23 | 2010-08-05 | Dongsu Park | Modified dendritic cells having enhanced survival and immunogenicity and related compositions and methods |
EP1862538A1 (en) * | 2006-05-29 | 2007-12-05 | IMBA-Institut für Molekulare Biotechnologie GmbH | siRNA kinase and methods of use |
ES2379603T3 (en) | 2006-05-30 | 2012-04-27 | Antibodyshop A/S | Methods for rapid assessment of the severity of trauma |
US7862812B2 (en) * | 2006-05-31 | 2011-01-04 | Lpath, Inc. | Methods for decreasing immune response and treating immune conditions |
EP2924440A3 (en) | 2006-06-07 | 2016-03-09 | Health Diagnostic Laboratory, Inc. | Markers associated with arteriovascular events and methods of use thereof |
US8101721B2 (en) * | 2006-06-15 | 2012-01-24 | Fibron Ltd. | Antibodies blocking fibroblast growth factor receptor activation and methods of use thereof |
WO2007150069A2 (en) | 2006-06-23 | 2007-12-27 | Myriad Genetics, Inc. | Dpyd gene variants and use thereof |
US8304384B2 (en) | 2006-06-28 | 2012-11-06 | Yeda Research And Development Co., Ltd | Caspase-8 and inflammation, infection and wound healing |
US7572618B2 (en) | 2006-06-30 | 2009-08-11 | Bristol-Myers Squibb Company | Polynucleotides encoding novel PCSK9 variants |
US20080004410A1 (en) * | 2006-06-30 | 2008-01-03 | Yu-Chin Lai | Hydrophilic macromonomers having alpha,beta-conjugated carboxylic terminal group and medical devices incorporating same |
RU2009104460A (en) * | 2006-07-11 | 2010-08-20 | Маск Фаундейшн Фор Рисерч Дивелопмент (Us) | FORECASTING OF HEART FAILURE AFTER MYOCARDIAL INFARCTION BY PROTEASES AND PROTEAZ INHIBITORS |
MY150687A (en) | 2006-07-21 | 2014-02-28 | Femalon S P R L | Assay and kit for predicting implantation success in assisted fertilisation |
EP1882697B1 (en) | 2006-07-24 | 2010-04-21 | Institut Pasteur | Antibodies, antibody fragments and scFv binding to post-translationally modified neurotrophins |
EP2602624A1 (en) * | 2006-08-07 | 2013-06-12 | Antibodyshop A/S | Diagnostic test to exclude significant renal injury |
EP2053961A4 (en) * | 2006-08-09 | 2013-05-01 | Biogen Idec Inc | Method for distribution of a drug |
US7939636B2 (en) * | 2006-08-11 | 2011-05-10 | Cell Signaling Technology, Inc. | Reagents for the detection of protein phosphorylation in c-Src signaling pathways |
US7993832B2 (en) * | 2006-08-14 | 2011-08-09 | Xdx, Inc. | Methods and compositions for diagnosing and monitoring the status of transplant rejection and immune disorders |
US20090258442A1 (en) * | 2006-08-31 | 2009-10-15 | Cell Signaling Technology, Inc. | Reagents for the detection of protein phosphorylation in carcinoma signaling pathways |
US20100267052A1 (en) * | 2006-09-01 | 2010-10-21 | American Type Culture Collection | Compositions and methods for diagnosis and treatment of type 2 diabetes |
US7951776B2 (en) * | 2006-09-01 | 2011-05-31 | American Type Culture Collection | Methods for treatment of type 1 diabetes |
US20080300170A1 (en) * | 2006-09-01 | 2008-12-04 | Cohava Gelber | Compositions and methods for diagnosis and treatment for type 2 diabetes |
US20090203602A1 (en) * | 2006-09-01 | 2009-08-13 | Cohava Gelber | Compositions and methods for diagnosis and treatment of type 2 diabetes |
US7569396B1 (en) | 2006-09-08 | 2009-08-04 | Purplecow Llc | Caffeine detection using internally referenced competitive assays |
US20100190689A1 (en) | 2006-09-21 | 2010-07-29 | University Of Rochester | Compositions and methods related to protein displacement therapy for myotonic distrophy |
LT2081595T (en) | 2006-09-26 | 2019-07-10 | Genmab A/S | Anti-cd38 plus corticosteroids plus a non-corticosteroid chemotherapeutic for treating tumors |
SI2457929T1 (en) | 2006-10-04 | 2016-09-30 | Genentech, Inc. | ELISA for VEGF |
WO2008066626A2 (en) * | 2006-10-25 | 2008-06-05 | The Rockefeller University | METHODS FOR THE TREATMENT OF Aβ RELATED DISORDERS AND COMPOSITIONS THEREFOR |
CN101687031B (en) | 2006-10-27 | 2014-05-14 | 勒帕斯公司 | Compositions and methods for treating ocular diseases and conditions |
JP5795833B2 (en) * | 2006-10-27 | 2015-10-14 | エルパス・インコーポレイテッドLpath, Inc. | Compositions and methods for binding sphingosine-1-phosphate |
US8329399B2 (en) | 2006-10-27 | 2012-12-11 | Siu K W Michael | Endometrial biomarkers |
US20080125368A1 (en) * | 2006-10-31 | 2008-05-29 | Imperial Innovations Limited | Methods |
WO2008053486A1 (en) * | 2006-11-02 | 2008-05-08 | Sylvie Luria | Methods for screening for therapeutic molecules and use of the molecules therefrom |
AR063760A1 (en) | 2006-11-02 | 2009-02-18 | Genentech Inc | ANTI-FACTOR D HUMANIZED ANTIBODIES AND USES OF THE SAME |
WO2008140484A2 (en) * | 2006-11-09 | 2008-11-20 | Xdx, Inc. | Methods for diagnosing and monitoring the status of systemic lupus erythematosus |
US20100015665A1 (en) * | 2006-11-10 | 2010-01-21 | Ucb Pharma S.A. | Antibodies and diagnostics |
WO2008061013A2 (en) * | 2006-11-10 | 2008-05-22 | Amgen Inc. | Antibody-based diagnostics and therapeutics |
WO2008061130A2 (en) * | 2006-11-15 | 2008-05-22 | Ucp Biosciences, Inc. | An improved collecting and testing device and method of use |
US20100104511A1 (en) * | 2006-11-22 | 2010-04-29 | The Board Of Regents Of The University Of Texas System | Methods and compositions using chelator-antibody conjugates |
KR20090087486A (en) * | 2006-11-30 | 2009-08-17 | 디코드 제네틱스 이에이치에프 | Genetic susceptibility variants of type 2 diabetes mellitus |
US20110008347A1 (en) * | 2006-12-01 | 2011-01-13 | Agency For Science ,Technology And Research | Cancer-related protein kinases |
WO2008068780A2 (en) * | 2006-12-05 | 2008-06-12 | Decode Genetics Ehf. | Genetic markers for risk management of cardiac arrhythmia |
EP2099827B1 (en) | 2006-12-18 | 2018-11-21 | Genentech, Inc. | Antagonist anti-notch3 antibodies and their use in the prevention and treatment of notch3-related diseases |
US20090186034A1 (en) * | 2006-12-19 | 2009-07-23 | Genetech, Inc. | Gene expression markers for inflammatory bowel disease |
WO2008094370A2 (en) | 2006-12-22 | 2008-08-07 | University Of Utah Research Foundation | Method of detecting ocular diseases and pathologic conditions and treatment of same |
WO2008079322A1 (en) * | 2006-12-22 | 2008-07-03 | Beckman Coulter, Inc. | Methods, kits and materials for diagnosing disease states by measuring isoforms or proforms of myeloperoxidase |
AR064642A1 (en) * | 2006-12-22 | 2009-04-15 | Wyeth Corp | POLINUCLEOTIDE VECTOR THAT INCLUDES IT RECOMBINATING CELL THAT UNDERSTANDS THE VECTOR POLYPEPTIDE, ANTIBODY, COMPOSITION THAT UNDERSTANDS THE POLINUCLEOTIDE, VECTOR, RECOMBINATING CELL POLYPEPTIDE OR ANTIBODY, USE OF THE COMPOSITION AND A COMPOSITION AND A METHOD |
US20090142342A1 (en) * | 2006-12-27 | 2009-06-04 | Johns Hopkins University | B7-h4 receptor agonist compositions and methods for treating inflammation and auto-immune diseases |
JP5481199B2 (en) | 2006-12-27 | 2014-04-23 | ザ ジョンズ ホプキンス ユニバーシティー | Compositions and methods for treating inflammation and autoimmune diseases |
US7989173B2 (en) | 2006-12-27 | 2011-08-02 | The Johns Hopkins University | Detection and diagnosis of inflammatory disorders |
US8506499B2 (en) * | 2007-01-04 | 2013-08-13 | Musc Foundation For Research Development | Predicting atrial fibrillation recurrence by protease and protease inhibitor profiling |
US8930178B2 (en) | 2007-01-04 | 2015-01-06 | Children's Hospital Medical Center | Processing text with domain-specific spreading activation methods |
MX2009008104A (en) * | 2007-02-02 | 2009-08-07 | Amgen Inc | Hepcidin, hepcidin antagonists and methods of use. |
NZ579401A (en) | 2007-02-07 | 2012-03-30 | Decode Genetics Ehf | Genetic variants contributing to risk of prostate cancer |
SG178811A1 (en) * | 2007-02-21 | 2012-03-29 | Decode Genetics Ehf | Genetic susceptibility variants associated with cardiovascular disease |
US20090081659A1 (en) | 2007-03-07 | 2009-03-26 | Cell Signaling Technology, Inc. | Reagents for the detection of protein phosphorylation in carcinoma signaling pathways |
WO2008113363A1 (en) * | 2007-03-21 | 2008-09-25 | Bioporto Diagnostics A/S | Diagnostic test for renal injury |
US7960139B2 (en) | 2007-03-23 | 2011-06-14 | Academia Sinica | Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells |
EP1975184A3 (en) | 2007-03-26 | 2008-11-26 | Cell Signaling Technology, Inc. | Serine or threonine phosphorylation sites |
WO2008117314A2 (en) * | 2007-03-26 | 2008-10-02 | Decode Genetics Ehf | Genetic variants on chr2 and chr16 as markers for use in breast cancer risk assessment, diagnosis, prognosis and treatment |
US20090092631A1 (en) * | 2007-03-26 | 2009-04-09 | Tripep Ab | Glycosylated specificity exchangers that induce an antibody dependent cellular cytotoxicity (adcc) response |
WO2008118324A2 (en) | 2007-03-26 | 2008-10-02 | Macrogenics, Inc. | Composition and method of treating cancer with an anti-uroplakin ib antibody |
PL2140269T3 (en) | 2007-03-27 | 2014-07-31 | Immunovia Ab | Protein signature/markers for the detection of adenocarcinoma |
US20080238709A1 (en) * | 2007-03-28 | 2008-10-02 | Faramarz Vaziri | One-way communication apparatus with dynamic key generation |
EP2144935A2 (en) | 2007-03-29 | 2010-01-20 | Technion Research & Development Foundation Ltd. | Antibodies, methods and kits for diagnosing and treating melanoma |
EP2132339B1 (en) * | 2007-04-04 | 2011-03-09 | Chimera Biotec GmbH | Method for the detection of an analyte in biological matrix |
BRPI0810893A2 (en) * | 2007-04-11 | 2014-10-29 | Alcon Res Ltd | Use of TNF-alpha inhibitor to an antihistamine to treat allergic rhinitis and conjunctivitis, and pharmaceutical composition comprising said compounds. |
US20090182035A1 (en) * | 2007-04-11 | 2009-07-16 | Alcon Research, Ltd. | Use of a combination of olopatadine and cilomilast to treat non-infectious rhinitis and allergic conjunctivitis |
BRPI0810409A2 (en) | 2007-04-18 | 2015-02-18 | Thethys Bioscience Inc | DIABETES-RELATED BIOMARKERS AND METHODS OF USE |
EP1983002A3 (en) | 2007-04-19 | 2009-03-11 | Peter Hornbeck | Tyrosine phosphorylation sites and antibodies specific for them |
EP1983003A3 (en) | 2007-04-19 | 2009-03-11 | Peter Hornbeck | Tyrosine phosphorylation sites and antibodies specific for them |
US7977462B2 (en) | 2007-04-19 | 2011-07-12 | Cell Signaling Technology, Inc. | Tyrosine phosphorylation sites |
EP2139916A1 (en) | 2007-04-26 | 2010-01-06 | Opsona Therapeutics Limited | Toll-like receptor binding epitope and compositions for binding thereto |
US20090004677A1 (en) * | 2007-04-27 | 2009-01-01 | The Board Of Trustees Of The University Of Illinois | Quantitative determination of bcl10 |
CA2685875C (en) * | 2007-05-01 | 2015-10-06 | Hill's Pet Nutrition, Inc. | Methods and compositions for diagnosing osteoarthritis in a feline |
US20090053831A1 (en) | 2007-05-01 | 2009-02-26 | Cell Signaling Technology, Inc. | Tyrosine phosphorylation sites |
GB0709092D0 (en) * | 2007-05-11 | 2007-06-20 | Borrebaeck Carl | Diagnosis and method of disease |
WO2008141318A1 (en) * | 2007-05-14 | 2008-11-20 | Dr. Susan Love Research Foundation | Device for determining risk of developing breast cancer and method thereof |
EP2535425A1 (en) | 2007-05-25 | 2012-12-19 | Decode Genetics EHF. | Variantes génétiques sur les chr 10q26 utilisées comme marqueurs dans l'évaluation, le diagnostic, le pronostic et le traitement d'un risque de cancer du sein |
WO2008150841A1 (en) | 2007-05-30 | 2008-12-11 | Lpath, Inc. | Compositions and methods for binding lysophosphatidic acid |
US9163091B2 (en) * | 2007-05-30 | 2015-10-20 | Lpath, Inc. | Compositions and methods for binding lysophosphatidic acid |
US8697350B2 (en) * | 2007-06-04 | 2014-04-15 | Diagnoplex | Biomarker combinations for colorectal cancer |
BRPI0812400A2 (en) | 2007-06-05 | 2014-10-29 | Univ Yale | UNIT, HYBRIDOMA, PHARMACEUTICAL COMPOSITION, METHOD FOR IDENTIFYING A UNIT, ANTIBODY ISOLATED TO A SAME ANTIGEN CONNECTION UNIT, PEPTIDES MOLECULE, AND UNIT USE. |
PL2171090T3 (en) | 2007-06-08 | 2013-09-30 | Genentech Inc | Gene expression markers of tumor resistance to her2 inhibitor treatment |
US20100294665A1 (en) * | 2007-07-12 | 2010-11-25 | Richard Allen | Method and system for transferring and/or concentrating a sample |
EP2514762B1 (en) | 2007-07-13 | 2015-04-08 | The Johns Hopkins University | B7-DC variants |
EP2185593B1 (en) * | 2007-07-25 | 2017-12-13 | Alexion Pharmaceuticals, Inc. | Compositions for treating autoimmune disease |
CN101848724A (en) | 2007-08-03 | 2010-09-29 | 奥普索纳医疗有限公司 | The purposes of TRL-2 antagonist in treatment reperfusion injury and tissue injury |
EP2185195A2 (en) * | 2007-08-16 | 2010-05-19 | Tripep Ab | Immunogen platform |
CN111909273B (en) | 2007-08-29 | 2024-03-26 | 塞诺菲-安万特股份有限公司 | humanized anti-CXCR 5 antibodies, derivatives thereof and uses thereof |
PT2769729T (en) | 2007-09-04 | 2019-05-08 | Compugen Ltd | Polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics |
US20090111131A1 (en) * | 2007-09-13 | 2009-04-30 | Seth Fishman | Method of detecting protein losing enteropathy in animals |
CL2008002775A1 (en) | 2007-09-17 | 2008-11-07 | Amgen Inc | Use of a sclerostin binding agent to inhibit bone resorption. |
US8114681B2 (en) | 2007-10-05 | 2012-02-14 | Affymetrix, Inc. | Highly multiplexed particle-based assays |
WO2009047809A2 (en) * | 2007-10-12 | 2009-04-16 | Decode Genetics Ehf | Sequence variants for inferring human pigmentation patterns |
EP2050764A1 (en) | 2007-10-15 | 2009-04-22 | sanofi-aventis | Novel polyvalent bispecific antibody format and uses thereof |
EP3072963B1 (en) | 2007-10-18 | 2020-04-01 | Cell Signaling Technology, Inc. | Translocation and mutant ros kinase in human non-small cell lung carcinoma |
AU2008316811B2 (en) | 2007-10-23 | 2015-01-22 | The Cleveland Clinic Foundation | Oxidant resistant apolipoprotein A-1 and mimetic peptides |
US8361465B2 (en) * | 2007-10-26 | 2013-01-29 | Lpath, Inc. | Use of anti-sphingosine-1-phosphate antibodies in combination with chemotherapeutic agents |
PT2514436T (en) | 2007-11-07 | 2018-03-21 | Genentech Inc | Il-22 for use in treating microbial disorders |
BRPI0819262A2 (en) | 2007-11-08 | 2017-05-02 | Neogenix Oncology Inc | recombinant monoclonal antibodies and corresponding antigens for colon and pancreatic cancers |
EP2215481B2 (en) * | 2007-11-15 | 2017-01-18 | Bioporto Diagnostics A/S | Diagnostic use of individual molecular forms of a biomarker |
JP5580205B2 (en) | 2007-11-19 | 2014-08-27 | セレラ コーポレーション | Lung cancer markers and their use |
US20090203043A1 (en) | 2007-11-21 | 2009-08-13 | Peter Hornbeck | Protein phosphorylation by basophilic serine/threonine kinases in insulin signaling pathways |
US8912149B1 (en) | 2007-11-28 | 2014-12-16 | California Institute Of Technology | Glycosaminoglycan mimetics |
KR20110015409A (en) | 2007-11-29 | 2011-02-15 | 제넨테크, 인크. | Gene expression markers for inflammatory bowel disease |
US8697360B2 (en) | 2007-11-30 | 2014-04-15 | Decode Genetics Ehf. | Genetic variants on CHR 11Q and 6Q as markers for prostate and colorectal cancer predisposition |
CA2707026C (en) | 2007-12-07 | 2017-04-11 | Zymogenetics, Inc. | Anti-human il-21 monoclonal antibodies |
PL2231861T3 (en) | 2007-12-13 | 2015-04-30 | Philip Morris Products Sa | Transgenic plants modified for reduced cadmium transport, derivative products, and related methods |
CA2707400A1 (en) * | 2007-12-14 | 2009-06-25 | Amgen Inc. | Method for treating bone fracture with anti-sclerostin antibodies |
EP2238251B1 (en) | 2007-12-27 | 2015-02-11 | Protiva Biotherapeutics Inc. | Silencing of polo-like kinase expression using interfering rna |
DE202008000834U1 (en) | 2008-01-21 | 2008-05-29 | Chin, Li-Te | Composition and reagent for CTLA-4 and uses thereof |
JP5701064B2 (en) | 2008-01-25 | 2015-04-15 | アムジエン・インコーポレーテツド | Ferroportin antibody and method of use thereof |
AU2009208607B2 (en) * | 2008-01-31 | 2013-08-01 | Compugen Ltd. | Polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics |
CA2618163A1 (en) | 2008-02-07 | 2009-08-07 | K. W. Michael Siu | Head and neck cancer biomarkers |
AU2009213689B2 (en) | 2008-02-14 | 2014-11-20 | Decode Genetics Ehf. | Susceptibility variants for lung cancer |
CN103884840A (en) * | 2008-02-21 | 2014-06-25 | 艾瑞斯国际有限公司 | Method for early determination of recurrence after therapy for prostate cancer |
WO2009111315A2 (en) * | 2008-02-29 | 2009-09-11 | Mayo Foundation For Medical Education And Research | Methods for reducing granulomatous inflammation |
US20090220991A1 (en) * | 2008-02-29 | 2009-09-03 | Cell Signaling Technology, Inc. | Reagents for the detection of protein phosphorylation in leukemia signaling pathways |
AU2009258038A1 (en) | 2008-03-14 | 2009-12-17 | Eastern Virginia Medical School | Imaging mass spectrometry for improved prostate cancer diagnostics |
US8993231B2 (en) * | 2008-03-18 | 2015-03-31 | Marshall University Research Corporation | Methods for stem cell production and therapy |
EP2274450A2 (en) | 2008-04-01 | 2011-01-19 | Decode Genetics EHF | Susceptibility variants for peripheral arterial disease and abdominal aortic aneurysm |
EP3045475B1 (en) | 2008-04-02 | 2017-10-04 | MacroGenics, Inc. | Bcr-complex-specific antibodies and methods of using same |
US8802093B2 (en) | 2008-04-02 | 2014-08-12 | Macrogenics, Inc. | HER2/neu-specific antibodies and methods of using same |
HUE036780T2 (en) | 2008-04-09 | 2018-07-30 | Genentech Inc | Novel compositions and methods for the treatment of immune related diseases |
AU2009234389B2 (en) | 2008-04-10 | 2014-08-21 | Cell Signaling Technology, Inc. | Compositions and methods for detecting EGFR mutations in cancer |
CA2721380A1 (en) | 2008-04-15 | 2009-10-22 | Protiva Biotherapeutics, Inc. | Silencing of csn5 gene expression using interfering rna |
PL2279254T3 (en) | 2008-04-15 | 2017-11-30 | Protiva Biotherapeutics Inc. | Novel lipid formulations for nucleic acid delivery |
WO2009130588A2 (en) * | 2008-04-22 | 2009-10-29 | Tripep Ab | Immunogen platform |
KR101837329B1 (en) | 2008-04-25 | 2018-03-09 | 다이액스 코포레이션 | Antibodies against fcrn and use thereof |
CR20170001A (en) | 2008-04-28 | 2017-08-10 | Genentech Inc | ANTI FACTOR D HUMANIZED ANTIBODIES |
ES2487846T3 (en) | 2008-05-01 | 2014-08-25 | Amgen, Inc. | Anti-hepcindin antibodies and methods of use |
EP2116261A1 (en) | 2008-05-07 | 2009-11-11 | Institut Pasteur | Sub-region of a plasmodium protein with improved vaccine potential and medical uses thereof |
WO2009137664A1 (en) | 2008-05-07 | 2009-11-12 | Eutropics Pharmaceuticals, Inc. | Antibodies specific to heterodimers of bcl-2 family and uses thereof |
JP2010043063A (en) | 2008-05-09 | 2010-02-25 | Agency For Science Technology & Research | Diagnosis and treatment of kawasaki disease |
WO2009148896A2 (en) | 2008-05-29 | 2009-12-10 | Nuclea Biotechnologies, LLC | Anti-phospho-akt antibodies |
CA2726845C (en) | 2008-06-04 | 2017-09-26 | Macrogenics, Inc. | Antibodies with altered binding to fcrn and methods of using same |
JOP20190083A1 (en) | 2008-06-04 | 2017-06-16 | Amgen Inc | Fgf21 mutant fusion polypeptides and uses thereof |
US20110123542A1 (en) * | 2008-06-24 | 2011-05-26 | Hadasit Medical Research Services And Development Ltd. | Ccl20-specific antibodies for cancer therapy |
HUE032894T2 (en) | 2008-06-25 | 2017-11-28 | Esbatech Alcon Biomed Res Unit | Stable and soluble antibodies inhibiting vegf |
RU2567100C2 (en) * | 2008-06-25 | 2015-10-27 | ИЭсБиЭйТЕК, ЭН АЛЬКОН БАЙОМЕДИКАЛ РИСЕРЧ ЮНИТ ЭлЭлСи | STABLE AND SOLUBLE ANTIBODIES INHIBITING TNFα |
US20110182881A1 (en) * | 2008-06-26 | 2011-07-28 | Dana-Farber Cancer Institute, Inc. | Signature and determinants associated with metastasis and methods of use thereof |
CA2729012A1 (en) | 2008-06-27 | 2009-12-30 | Amgen Inc. | Ang-2 inhibition to treat multiple sclerosis |
US20110111419A1 (en) * | 2008-07-04 | 2011-05-12 | deCODE Geneties ehf. | Copy Number Variations Predictive of Risk of Schizophrenia |
US8951735B2 (en) | 2008-07-07 | 2015-02-10 | Decode Genetics Ehf. | Genetic variants for breast cancer risk assessment |
AU2009268659A1 (en) | 2008-07-08 | 2010-01-14 | Genomic Health, Inc. | Gene expression profiling for predicting the survivability of prostate cancer subjects |
WO2010009271A2 (en) | 2008-07-15 | 2010-01-21 | Academia Sinica | Glycan arrays on ptfe-like aluminum coated glass slides and related methods |
AU2009270682B2 (en) | 2008-07-17 | 2016-04-21 | Ikfe Lnstitut Fur Klinische Forschung Und Entwicklung Gmbh | Biomarkers for insulin resistance and beta-cell dysfunction |
EP2338051B1 (en) | 2008-07-17 | 2013-11-20 | IKFE Institut für klinische Forschung und Entwicklung GmbH | Biomarkers for cardiodiabetes |
US20100021472A1 (en) * | 2008-07-25 | 2010-01-28 | Geetha Srikrishna | Methods for diagnosing and treating cancer |
US8795981B2 (en) | 2008-08-08 | 2014-08-05 | Molecular Devices, Llc | Cell detection |
JP2011530306A (en) * | 2008-08-12 | 2011-12-22 | ディコーデ ジェネテクス イーエイチエフ | Genetic variation useful for risk assessment of thyroid cancer |
EP2329037B1 (en) * | 2008-08-15 | 2015-01-28 | Decode Genetics EHF | Genetic variants predictive of cancer risk |
CA2734892A1 (en) | 2008-08-18 | 2010-02-25 | Seoul National University Industry Foundation | Method for controlling cancer metastasis or cancer cell migration by modulating the cellular level of lysyl trna synthetase |
PE20110435A1 (en) | 2008-08-25 | 2011-07-20 | Amplimmune Inc | ANTAGONIST COMPOSITIONS OF PD-1 |
AU2009288289B2 (en) * | 2008-08-25 | 2012-11-08 | Amplimmune, Inc. | PD-1 antagonists and methods of use thereof |
BRPI0823049A2 (en) | 2008-09-07 | 2015-06-16 | Glyconex Inc | Anti-extended type 1 glycosphingolipid antibodies, derivatives thereof and use. |
WO2010030813A2 (en) | 2008-09-10 | 2010-03-18 | Genentech, Inc. | Methods for inhibiting ocular angiogenesis |
US20110236314A1 (en) | 2008-09-12 | 2011-09-29 | Cancer Research Initiatives Foundation | Method of detection and diagnosis of oral and nasopharyngeal cancers |
US8417011B2 (en) * | 2008-09-18 | 2013-04-09 | Molecular Devices (New Milton) Ltd. | Colony detection |
WO2010042815A2 (en) * | 2008-10-09 | 2010-04-15 | Duke University | Vhh antibody fragments for use in the detection and treatment of cancer |
MX341149B (en) | 2008-10-10 | 2016-08-09 | Amgen Inc | Fgf21 mutants and uses thereof. |
EP2349329A4 (en) | 2008-10-14 | 2012-10-31 | Dyax Corp | Use of igf-ii/igf-iie binding for the treatment and prevention of systemic sclerosis associated pulmonary fibrosis |
US8147847B2 (en) * | 2008-10-21 | 2012-04-03 | International Vaccine Institute | Shigella protein antigens and methods |
US8871202B2 (en) | 2008-10-24 | 2014-10-28 | Lpath, Inc. | Prevention and treatment of pain using antibodies to sphingosine-1-phosphate |
BRPI0921286B8 (en) | 2008-11-05 | 2022-10-25 | Wyeth Llc | MULTIPLE COMPONENT IMMUNOGENIC COMPOSITION FOR THE PREVENTION OF BETA-HEMOLYTIC STREPTOCOCCAL (BHS) DISEASE. |
CA2742802C (en) | 2008-11-10 | 2019-11-26 | Alexion Pharmaceuticals, Inc. | Methods and compositions for treating complement-associated disorders |
AT507604A1 (en) | 2008-11-19 | 2010-06-15 | Affiris Forschungs & Entwicklungs Gmbh | TREATMENT OF ATHEROSCLEROSIS |
DK2189539T4 (en) * | 2008-11-21 | 2018-09-17 | Chimera Biotec Gmbh | Conjugate complexes for analyte detection |
RU2011121042A (en) | 2008-11-26 | 2013-01-10 | Файв Прайм Терапеутикс, Инк. | COMPOSITIONS AND METHODS OF REGULATING EXPRESSION OF COLLAGEN AND ACT OF SMOOTH MUSCLES BY SERPINE2 |
WO2010061393A1 (en) | 2008-11-30 | 2010-06-03 | Compugen Ltd. | He4 variant nucleotide and amino acid sequences, and methods of use thereof |
AU2009323996A1 (en) | 2008-12-03 | 2011-07-07 | Institut Pasteur | Use of phenol-soluble modulins for vaccine development |
CA2743707A1 (en) | 2008-12-04 | 2010-06-10 | Pioneer Hi-Bred International, Inc. | Methods and compositions for enhanced yield by targeted expression of knotted1 |
WO2010064250A1 (en) | 2008-12-04 | 2010-06-10 | Yeda Research And Development Co. Ltd. | Compositions and methods for diagnosing and treating cancer and neurodegenerative diseases related to beclin-1 |
CA2782776A1 (en) | 2008-12-04 | 2010-06-10 | Ikfe Gmbh | Biomarkers for atherosclerosis |
CA2745492A1 (en) | 2008-12-08 | 2010-06-17 | Compugen Ltd. | A polyclonal or monoclonal antibody or antibody binding fragment that binds to a tmem154 polypeptide |
US20110118134A1 (en) | 2008-12-11 | 2011-05-19 | Ikfe Gmbh | Biomarkers for insulin sensitizer drug response |
US20100209350A1 (en) | 2008-12-30 | 2010-08-19 | Andreas Pfuetzner | Biomarkers for Adipose Tissue Activity |
WO2010079428A2 (en) | 2009-01-07 | 2010-07-15 | Ikfe Gmbh | Biomarkers for appetite regulation |
JPWO2010087131A1 (en) | 2009-01-28 | 2012-08-02 | 学校法人東海大学 | HIV replication inhibitor and use thereof |
EP2391653B8 (en) | 2009-01-28 | 2015-09-30 | Industrial Technology Research Institute | Biomarkers associated with nephropathy |
JP2012517238A (en) | 2009-02-11 | 2012-08-02 | カリス エムピーアイ インコーポレイテッド | Molecular profiling of tumors |
US20110014190A1 (en) | 2009-02-12 | 2011-01-20 | Human Genome Sciences, Inc. | Use of b lymphocyte stimulator protein antagonists to promote transplantation tolerance |
CA2744236C (en) | 2009-02-12 | 2021-03-16 | Cell Signaling Technology, Inc. | Mutant ros expression in human cancer |
PL2939683T3 (en) | 2009-02-16 | 2017-07-31 | Cerenis Therapeutics Holding Sa | Apolipoprotein A-I Mimics |
US20100248265A1 (en) * | 2009-02-27 | 2010-09-30 | The Salk Institute For Biological Studies | Compositions and methods for diagnosis and treatment of cancer |
US8772238B2 (en) | 2009-03-18 | 2014-07-08 | The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Use of ixolaris, a tissue factor inhibitor, for the treatment of cancer |
EP2233496A1 (en) | 2009-03-26 | 2010-09-29 | Ruhr-Universität Bochum | Fluorescent proteins |
CA2756760A1 (en) * | 2009-03-27 | 2010-11-04 | Gojo Industries, Inc. | Compositions and methods for screening and using compounds antagonizing spore-surface interactions |
WO2010112033A2 (en) | 2009-03-31 | 2010-10-07 | Østjysk Innovation A/S | Method for estimating the risk of having or developing multiple sclerosis using sequence polymorphisms in a specific region of chromosome x |
US8795963B2 (en) | 2009-04-03 | 2014-08-05 | Decode Genetics Ehf. | Genetic markers for risk management of atrial fibrillation and stroke |
AU2010246038A1 (en) | 2009-05-05 | 2011-12-01 | Amgen Inc. | FGF21 mutants and uses thereof |
SI3248610T1 (en) | 2009-05-05 | 2024-03-29 | Amgen Inc., | Fgf21 mutants and uses thereof |
US20110301093A1 (en) | 2009-05-06 | 2011-12-08 | Yeda Research And Development Co. Ltd. At The Weizmann Institute Of Science | Compositions and methods for diagnosing and treating cancer and neurodegenerative diseases related to beclin-1 |
EP2451975A4 (en) * | 2009-05-08 | 2013-08-14 | Decode Genetics Ehf | Genetic variants contributing to risk of prostate cancer |
WO2010148142A1 (en) | 2009-06-17 | 2010-12-23 | Amgen Inc. | Chimeric fgf19 polypeptides and uses thereof |
WO2010151823A1 (en) | 2009-06-25 | 2010-12-29 | Savient Pharmaceuticals Inc. | Methods and kits for predicting infusion reaction risk and antibody-mediated loss of response by monitoring serum uric acid during pegylated uricase therapy |
WO2011000805A1 (en) | 2009-06-29 | 2011-01-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Biomarkers of oocyte competency and method of use |
IL199618A0 (en) | 2009-06-29 | 2010-04-29 | Two To Biotech Ltd | Novel antibodies and their use in diagnostic methods |
EP2449114B9 (en) | 2009-07-01 | 2017-04-19 | Protiva Biotherapeutics Inc. | Novel lipid formulations for delivery of therapeutic agents to solid tumors |
IE20090514A1 (en) | 2009-07-06 | 2011-02-16 | Opsona Therapeutics Ltd | Humanised antibodies and uses therof |
WO2011004379A1 (en) | 2009-07-10 | 2011-01-13 | Tel Hashomer Medical Research Infrastructure And Services Ltd. | Compositions and methods for treating cancer |
AU2010269841A1 (en) | 2009-07-10 | 2012-02-23 | Decode Genetics Ehf | Genetic markers associated with risk of diabetes mellitus |
SG177699A1 (en) | 2009-07-20 | 2012-02-28 | Genentech Inc | Gene expression markers for crohn's disease |
US8716464B2 (en) | 2009-07-20 | 2014-05-06 | Thomas W. Geisbert | Compositions and methods for silencing Ebola virus gene expression |
US9493834B2 (en) | 2009-07-29 | 2016-11-15 | Pharnext | Method for detecting a panel of biomarkers |
IL200202A0 (en) | 2009-08-02 | 2010-05-31 | Orly Devary | Novel proteins |
US9499627B2 (en) | 2009-08-03 | 2016-11-22 | University Of Miami | Method for in vivo expansion of T regulatory cells |
US20120148604A1 (en) | 2009-08-20 | 2012-06-14 | Transposagen Biopharmaceuticals, Inc. | Trp inhibitors and uses thereof |
US20120183981A1 (en) * | 2009-08-28 | 2012-07-19 | Inova Diagnostics, Inc. | Methoed for detecting circulating cartilage oligomeric matrix protein in the diagnosis and monitoring of cirrhosis |
IN2012DN02753A (en) | 2009-08-31 | 2015-09-18 | Amplimmune Inc | |
DK2477652T3 (en) | 2009-09-16 | 2015-07-20 | Vaxart Inc | Immunization strategy for the prevention of infection H1Ni |
CA2775092A1 (en) | 2009-09-23 | 2011-03-31 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing genes expressed in cancer |
JP5885664B2 (en) | 2009-09-25 | 2016-03-15 | ゾーマ テクノロジー リミテッド | Screening method |
US8926976B2 (en) | 2009-09-25 | 2015-01-06 | Xoma Technology Ltd. | Modulators |
AU2010300421B2 (en) * | 2009-10-01 | 2014-01-23 | Alcon Research, Ltd. | Olopatadine compositions and uses thereof |
CA2776756A1 (en) | 2009-10-11 | 2011-04-14 | Biogen Idec Ma Inc. | Anti-vla-4 related assays |
EP2488659B1 (en) | 2009-10-15 | 2019-12-11 | Crescendo Bioscience, Inc. | Biomarkers and methods for measuring and monitoring inflammatory disease activity |
US20120263719A1 (en) | 2009-10-22 | 2012-10-18 | Yeda Research And Development Co., Ltd. | Compositions and methods for treating aspergillosis |
CN110054692A (en) | 2009-10-23 | 2019-07-26 | 米伦纽姆医药公司 | Anti- GCC antibody molecule and its compositions related and method |
WO2011056606A1 (en) * | 2009-10-26 | 2011-05-12 | Genentech, Inc. | Assays for detecting antibodies specific to therapeutic anti-ige antibodies and their use in anaphylaxis |
EP2494077A4 (en) | 2009-10-27 | 2013-08-21 | Caris Mpi Inc | Molecular profiling for personalized medicine |
JP2013509588A (en) | 2009-10-29 | 2013-03-14 | テシス バイオサイエンス, インコーポレイテッド | Protein biomarkers and lipid metabolite biomarkers provide consistent improvement for the prevention of type 2 diabetes |
EP2494483A2 (en) | 2009-10-29 | 2012-09-05 | Tethys Bioscience, Inc. | Method for determining risk of diabetes |
WO2011058367A2 (en) | 2009-11-13 | 2011-05-19 | Astrazeneca Ab | Diagnostic test for predicting responsiveness to treatment with poly(adp-ribose) polymerase (parp) inhibitor |
US8592151B2 (en) * | 2009-11-17 | 2013-11-26 | Musc Foundation For Research Development | Assessing left ventricular remodeling via temporal detection and measurement of microRNA in body fluids |
US9428586B2 (en) | 2009-12-01 | 2016-08-30 | Compugen Ltd | Heparanase splice variant |
US11377485B2 (en) | 2009-12-02 | 2022-07-05 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
US10087236B2 (en) | 2009-12-02 | 2018-10-02 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
AU2010326024A1 (en) * | 2009-12-02 | 2012-07-05 | Amgen Inc. | Binding proteins that bind to human FGFR1c, human beta-Klotho and both human FGFR1c and human beta-Klotho |
RU2707126C2 (en) | 2009-12-07 | 2019-11-22 | Пирис Аг | Human lipolocal 2 malletes (lcn2, hngal) with affinity for specific target |
UA109888C2 (en) * | 2009-12-07 | 2015-10-26 | ANTIBODY OR ANTIBODILITY ANTIBODY OR ITS BINDING TO THE β-CLOTE, FGF RECEPTORS AND THEIR COMPLEXES | |
EP2516995B1 (en) | 2009-12-22 | 2016-10-26 | Agency For Science, Technology And Research | Sers-based analyte detection |
HUE028629T2 (en) | 2009-12-23 | 2016-12-28 | Synimmune Gmbh | Anti-flt3 antibodies and methods of using the same |
ES2688093T3 (en) | 2010-01-06 | 2018-10-30 | Dyax Corp. | Plasma kallikrein binding proteins |
US11287423B2 (en) | 2010-01-11 | 2022-03-29 | Biogen Ma Inc. | Assay for JC virus antibodies |
DK3339865T5 (en) | 2010-01-11 | 2023-03-20 | Biogen Ma Inc | JC VIRUS ANTIBODIES ASSAY |
KR20130005264A (en) | 2010-01-11 | 2013-01-15 | 알렉시온 파마슈티칼스, 인코포레이티드 | Biomarkers of immunomodulatory effects in humans treated with anti-cd200 antibodies |
WO2011089211A1 (en) | 2010-01-22 | 2011-07-28 | Synimmune Gmbh | Anti-cd133 antibodies and methods of using the same |
CA2784919A1 (en) | 2010-01-26 | 2011-07-26 | Banyan Biomarkers, Inc. | Compositions and methods relating to argininosuccinate synthetase |
AU2011210362B2 (en) | 2010-01-27 | 2015-09-10 | Yeda Research And Development Co. Ltd. | Antibodies that inhibit metalloproteins |
US20130071408A1 (en) | 2010-02-01 | 2013-03-21 | Atul J. Butte | Methods for Diagnosis and Treatment of Non-Insulin Dependent Diabetes Mellitus |
TWI518325B (en) | 2010-02-04 | 2016-01-21 | 自治醫科大學 | Identification, assessment, and therapy of cancers with innate or acquired resistance to alk inhibitors |
JP4686639B1 (en) * | 2010-02-25 | 2011-05-25 | 田中貴金属工業株式会社 | Raw pork detection method and detection kit |
WO2011106738A2 (en) | 2010-02-25 | 2011-09-01 | Fred Hutchinson Cancer Research Center | Use of tcr clonotypes as biomarkers for disease |
US20110212088A1 (en) * | 2010-02-26 | 2011-09-01 | Sabbadini Roger A | Anti-paf antibodies |
EP2544688B1 (en) | 2010-03-02 | 2016-09-07 | President and Fellows of Harvard College | Methods and compositions for treatment of angelman syndrome |
US20110237000A1 (en) * | 2010-03-11 | 2011-09-29 | Agency For Science, Technology And Research | Method for detecting an analyte molecule |
CA3079122A1 (en) | 2010-03-26 | 2011-09-29 | Trustees Of Dartmouth College | Vista regulatory t cell mediator protein, vista binding agents and use thereof |
US10745467B2 (en) | 2010-03-26 | 2020-08-18 | The Trustees Of Dartmouth College | VISTA-Ig for treatment of autoimmune, allergic and inflammatory disorders |
US20150231215A1 (en) | 2012-06-22 | 2015-08-20 | Randolph J. Noelle | VISTA Antagonist and Methods of Use |
EP2556169B1 (en) | 2010-04-07 | 2018-02-14 | Imperial Innovations Limited | Methods for categorising cancer such as breast cancer |
WO2011130332A1 (en) | 2010-04-12 | 2011-10-20 | Academia Sinica | Glycan arrays for high throughput screening of viruses |
WO2011130417A2 (en) | 2010-04-15 | 2011-10-20 | Amgen Inc. | HUMAN FGF RECEPTOR AND β-KLOTHO BINDING PROTEINS |
US8785385B2 (en) | 2010-04-19 | 2014-07-22 | Research Development Foundation | RTEF-1 variants and uses thereof |
WO2011132086A2 (en) | 2010-04-21 | 2011-10-27 | MeMed Diagnostics, Ltd. | Signatures and determinants for distinguishing between a bacterial and viral infection and methods of use thereof |
DK3195880T3 (en) | 2010-05-14 | 2020-03-02 | Amgen Inc | Highly Concentrated Anti-Sclerostin Antibody Formulations |
US8623376B2 (en) | 2010-05-14 | 2014-01-07 | Baxter International Inc. | Chimeric OspA genes, proteins, and methods of use thereof |
EP2572197A4 (en) | 2010-05-18 | 2013-08-28 | Texas A & M Univ Sys | Method and composition for the diagnosis and monitoring of inflammatory diseases |
WO2011146725A1 (en) | 2010-05-19 | 2011-11-24 | Bayer Healthcare Llc | Biomarkers for a multikinase inhibitor |
WO2011145085A2 (en) | 2010-05-21 | 2011-11-24 | Procognia (Israel) Ltd | Novel antibodies and methods of use for the treatment and diagnosis of cancer |
WO2011161545A2 (en) | 2010-06-04 | 2011-12-29 | The Netherlands Cancer Institute | Non-hydrolyzable protein conjugates, methods and compositions related thereto |
WO2011156715A2 (en) | 2010-06-10 | 2011-12-15 | The Regents Of The University Of Michigan | Methods of treating metabolic disorders and cardiovascular diseases |
GB201009798D0 (en) | 2010-06-11 | 2010-07-21 | Immunovia Ab | Method,array and use thereof |
WO2011163401A2 (en) | 2010-06-22 | 2011-12-29 | Neogenix Oncology, Inc. | Colon and pancreas cancer specific antigens and antibodies |
JP2013538555A (en) | 2010-07-15 | 2013-10-17 | テクニオン リサーチ アンド ディベロップメント ファウンデーション リミテッド | An isolated high affinity entity with T cell receptor-like specificity for a natural complex of MHC class II and glutamate decarboxylase (GAD) autoantigenic peptide |
US20130189284A1 (en) | 2010-07-15 | 2013-07-25 | Technion Research & Development Foundation Ltd. | Antibodies with t-cell receptor like specificity towards native complexes of mhc class ii and diabetes-associated autoantigenic peptides |
CA2807440A1 (en) | 2010-08-04 | 2012-02-09 | Cizzle Biotechnology Limited | Methods and compounds for the diagnosis and treatment of cancer |
WO2012019132A2 (en) | 2010-08-06 | 2012-02-09 | Cell Signaling Technology, Inc. | Anaplastic lymphoma kinase in kidney cancer |
US8956859B1 (en) | 2010-08-13 | 2015-02-17 | Aviex Technologies Llc | Compositions and methods for determining successful immunization by one or more vaccines |
US9040464B2 (en) | 2010-08-16 | 2015-05-26 | Mount Sinai Hosptial | Markers of the male urogenital tract |
EP4050109A1 (en) | 2010-08-18 | 2022-08-31 | Fred Hutchinson Cancer Center | Agents for use in treating facioscapulohumeral dystrophy (fshd) |
US10088490B2 (en) | 2010-08-20 | 2018-10-02 | Siemens Healthcare Diagnostics Inc. | Assay for analytes using multiple receptors |
PL3246044T3 (en) | 2010-08-23 | 2021-08-23 | Wyeth Llc | Stable formulations of neisseria meningitidis rlp2086 antigens |
WO2012030738A2 (en) | 2010-08-30 | 2012-03-08 | Beckman Coulter, Inc. | Complex phosphoprotein activation profiles |
US9982304B2 (en) | 2010-09-03 | 2018-05-29 | The Johns Hopkins University | ARID1A and PPP2R1A mutations in cancer |
GB201014837D0 (en) | 2010-09-07 | 2010-10-20 | Immunovia Ab | Biomarker signatures and uses thereof |
ES2728282T3 (en) | 2010-09-10 | 2019-10-23 | Wyeth Llc | Non-lipidated variants of ORF2086 antigens from Neisseria meningitidis |
EP2616100B1 (en) | 2010-09-17 | 2016-08-31 | Compugen Ltd. | Compositions and methods for treatment of drug resistant multiple myeloma |
WO2012038744A2 (en) | 2010-09-22 | 2012-03-29 | Genome Research Limited | Detecting mutations |
EP2622091B1 (en) | 2010-09-23 | 2019-03-13 | Precision Biologics, Inc. | Colon and pancreas cancer peptidomimetics |
US8497138B2 (en) | 2010-09-30 | 2013-07-30 | Genetix Limited | Method for cell selection |
US9006458B2 (en) | 2010-10-12 | 2015-04-14 | Agency For Science, Technology And Research | Surface Enhanced Raman Spectroscopy (SERS) compounds and methods of their preparation |
EP2444084A1 (en) | 2010-10-21 | 2012-04-25 | Centro Nacional de Investigaciones Oncológicas (CNIO) | Use of PI3K inibitors for the treatment of obesity |
CA2815416A1 (en) | 2010-10-21 | 2012-04-26 | Vertex Pharmaceuticals Incorporated | Biomarkers for hcv infected patients |
AR083495A1 (en) | 2010-10-22 | 2013-02-27 | Esbatech Alcon Biomed Res Unit | STABLE AND SOLUBLE ANTIBODIES |
GB201018014D0 (en) | 2010-10-26 | 2010-12-08 | Senzagen Ab | Analytical methods and arrays for use in the same |
ES2688457T3 (en) | 2010-10-28 | 2018-11-02 | Yeda Research And Development Co. Ltd. | Methods of generating antibodies against metalloenzymes |
WO2012068355A2 (en) | 2010-11-18 | 2012-05-24 | Tufts Medical Center, Inc. | Treating aortic aneurysm by modulating toll-like receptors |
EA034057B1 (en) | 2010-11-23 | 2019-12-23 | Пантерикс, Инк. | Method of reducing duration of diarrhea caused by enteric infection |
US8992908B2 (en) | 2010-11-23 | 2015-03-31 | Alderbio Holdings Llc | Anti-IL-6 antibodies for the treatment of oral mucositis |
EP2477032A1 (en) | 2011-01-18 | 2012-07-18 | Baxter International Inc | Measurement of anti-amyloid antibodies in human blood |
JP2014507649A (en) | 2011-01-18 | 2014-03-27 | バクスター・インターナショナル・インコーポレイテッド | Measurement of anti-β-amyloid antibody in human blood |
AU2012212066A1 (en) | 2011-02-03 | 2013-08-15 | Alexion Pharmaceuticals, Inc. | Use of an anti-CD200 antibody for prolonging the survival of allografts |
FR2971258B1 (en) | 2011-02-09 | 2020-12-04 | Bio Rad Pasteur | COMBINATION OF BIOMARKERS FOR THE PROGNOSIS OF A RESPONSE OR NON-RESPONSE TO ANTI-HCV TREATMENT |
FR2971257B1 (en) | 2011-02-09 | 2020-12-04 | Bio Rad Pasteur | COMBINATION OF BIOMARKERS FOR THE PROGNOSIS OF A RESPONSE OR NON-RESPONSE TO ANTI-HCV TREATMENT |
FR2971256A1 (en) | 2011-02-09 | 2012-08-10 | Bio Rad Pasteur | COMBINATION OF BIOMARKERS FOR THE DETECTION AND EVALUATION OF A HEPATIC FIBROSIS |
BR112013020875A2 (en) | 2011-02-15 | 2019-09-24 | Immune Design Corp | method for inducing a specific immune response to an immunogen in an individual. |
US8658171B2 (en) | 2011-02-28 | 2014-02-25 | Livzon Mabpharm Inc. | Humanized anti-TNFα antibodies |
CN102675460B (en) | 2011-02-28 | 2015-08-19 | 珠海市丽珠单抗生物技术有限公司 | The humanized antibody of Tumor necrosis factorα |
JP2014509588A (en) | 2011-03-01 | 2014-04-21 | アムジエン・インコーポレーテツド | Bispecific binding agent |
GB201103726D0 (en) | 2011-03-04 | 2011-04-20 | Immunovia Ab | Method, array and use thereof |
WO2012125623A2 (en) | 2011-03-14 | 2012-09-20 | Ludwig Institute For Cancer Research Ltd. | Cleavage inhibitors of transforming growth factor beta type i receptor and uses thereof in cancer therapy |
US20130344074A1 (en) | 2011-03-16 | 2013-12-26 | Sanofi | Uses of a dual v region antibody-like protein |
SG10201701634PA (en) | 2011-03-25 | 2017-04-27 | Amgen Inc | Anti - sclerostin antibody crystals and formulations thereof |
JP2014513289A (en) | 2011-04-08 | 2014-05-29 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | Biomarker for predicting therapeutic response to IFNβ and use thereof |
NZ616304A (en) | 2011-04-08 | 2016-01-29 | Immune Design Corp | Immunogenic compositions and methods of using the compositions for inducing humoral and cellular immune responses |
US9150644B2 (en) | 2011-04-12 | 2015-10-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Human monoclonal antibodies that bind insulin-like growth factor (IGF) I and II |
EP2697256A1 (en) | 2011-04-15 | 2014-02-19 | Compugen Ltd. | Polypeptides and polynucleotides, and uses thereof for treatment of immune related disorders and cancer |
MX2013012284A (en) | 2011-04-29 | 2013-11-21 | Bristol Myers Squibb Co | Ip-10 antibody dosage escalation regimens. |
GB201114858D0 (en) | 2011-08-29 | 2011-10-12 | Nvip Pty Ltd | Anti-nerve growth factor antibodies and methods of using the same |
CA2834983C (en) | 2011-05-06 | 2020-11-17 | Nvip Pty Ltd | Anti-nerve growth factor antibodies and methods of preparing and using the same |
CA2835094C (en) | 2011-05-06 | 2020-12-22 | David Gearing | Anti-nerve growth factor antibodies and methods of preparing and using the same |
EP4026845A1 (en) | 2011-05-06 | 2022-07-13 | Zoetis Services LLC | Anti-nerve growth factor antibodies and methods of preparing and using the same |
JP6258194B2 (en) | 2011-05-06 | 2018-01-10 | ネックスヴェット オーストラリア プロプライエタリー リミテッド | Anti-nerve growth factor antibodies and methods of making and using them |
WO2012156825A1 (en) | 2011-05-17 | 2012-11-22 | Genoscience Pharma | Peptide-based hiv pre-integration complex inhibitors |
MX347514B (en) | 2011-05-25 | 2017-04-28 | Innate Pharma Sa | Anti-kir antibodies for the treatment of inflammatory disorders. |
CA2837527C (en) | 2011-06-02 | 2019-05-28 | Dyax Corp. | Fc receptor binding proteins |
CN103765212A (en) | 2011-06-27 | 2014-04-30 | 杰克逊实验室 | Methods and compositions for treatment of cancer and autoimmune disease |
AU2012277376B2 (en) | 2011-06-30 | 2016-11-24 | Compugen Ltd. | Polypeptides and uses thereof for treatment of autoimmune disorders and infection |
EP2734543B1 (en) | 2011-07-24 | 2018-10-03 | Carmel-Haifa University Economic Corp. | Lactoferrin fragments and use thereof |
EP2737318B1 (en) | 2011-07-27 | 2017-03-01 | Bio-Rad Innovations | A2m fragments and applications thereof |
MX2014001354A (en) | 2011-08-02 | 2014-10-14 | Pfizer | Crizotinib for use in the treatment of cancer. |
WO2013019817A1 (en) | 2011-08-03 | 2013-02-07 | Quidel Corporation | N-acetyl-d-glucosamine for enhanced specificity of strep a immunoassay |
ES2667554T3 (en) | 2011-08-04 | 2018-05-11 | Amgen Inc. | Method for the treatment of bone space defects |
EP2748192B2 (en) | 2011-08-23 | 2022-04-20 | Foundation Medicine, Inc. | Kif5b-ret fusion molecules and uses thereof |
JP2014526902A (en) | 2011-08-30 | 2014-10-09 | エヌヴィーアイピー プロプライエタリー リミテッド | Canine tumor necrosis factor antibody and method of use thereof |
WO2013043012A2 (en) * | 2011-09-22 | 2013-03-28 | Medicinal Bioconvergence Research Center | Novel use of leucyl trna synthetase |
WO2013045863A1 (en) | 2011-09-29 | 2013-04-04 | Institut Pasteur | Detection of e.coli strains of serotype 0104 |
EP2581384A1 (en) | 2011-10-11 | 2013-04-17 | Institut Pasteur | Products useful for the treatment of malignant neoplasms of the human nervous system |
KR102102862B1 (en) | 2011-10-14 | 2020-04-22 | 제넨테크, 인크. | ANTI-HtrA1 ANTIBODIES AND METHODS OF USE |
EP2769223A1 (en) | 2011-10-17 | 2014-08-27 | Westfälische Wilhelms-Universität Münster | Assessment of pml risk and methods based thereon |
CN105063186A (en) | 2011-11-10 | 2015-11-18 | 霍夫曼-拉罗奇有限公司 | Methods for treating, diagnosing and monitoring Alzheimer's disease |
WO2013071066A1 (en) | 2011-11-11 | 2013-05-16 | The Broad Institute, Inc. | Signatures associated with the response to cancer therapy |
EP3441142A1 (en) | 2011-11-16 | 2019-02-13 | Becton, Dickinson and Company | Methods and systems for detecting an analyte in a sample |
JP6000369B2 (en) | 2011-11-29 | 2016-09-28 | テレフレックス メディカル インコーポレイテッドTeleflex Medical Incorporated | Integrated allergy testing instrument |
US9554736B2 (en) | 2011-11-29 | 2017-01-31 | Teleflex Medical Incorporated | Device with integrated allergy testing |
EP3483288B1 (en) | 2011-11-30 | 2022-03-16 | Children's Hospital Medical Center | Personalized pain management and anesthesia: preemptive risk identification |
CA2857114A1 (en) | 2011-11-30 | 2013-06-06 | Genentech, Inc. | Erbb3 mutations in cancer |
EP2790687B1 (en) | 2011-12-16 | 2018-08-29 | Poseida Therapeutics, Inc. | Trpc4 modulators for use in the treatment or prevention of pain |
US9035039B2 (en) | 2011-12-22 | 2015-05-19 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing SMAD4 |
EP2794626B3 (en) | 2011-12-22 | 2020-08-05 | GlycoMimetics, Inc. | E-selectin antagonist compounds |
SG10201509629QA (en) | 2011-12-28 | 2015-12-30 | Amgen Inc | Method Of Treating Alveolar Bone Loss Through The Use Of Anti-Sclerostin Antibodies |
SG11201403756PA (en) | 2012-01-01 | 2014-11-27 | Qbi Entpr Ltd | Endo180-targeted particles for selective delivery of therapeutic and diagnostic agents |
AU2013209492B2 (en) | 2012-01-20 | 2018-02-08 | Genzyme Corporation | Anti-CXCR3 antibodies |
EP2807271B1 (en) | 2012-01-24 | 2018-08-22 | CD Diagnostics, Inc. | System for detecting infection in synovial fluid |
MX2014009289A (en) | 2012-02-01 | 2015-09-08 | Compugen Ltd | C10rf32 antibodies, and uses thereof for treatment of cancer. |
ES2679107T3 (en) | 2012-02-09 | 2018-08-22 | Memed Diagnostics Ltd. | Badges and determinants to diagnose infections and methods to use them |
BR112014020824B1 (en) | 2012-02-24 | 2022-10-04 | Protiva Biotherapeutics Inc | LIPID, LIPID PARTICLE AND PHARMACEUTICAL COMPOSITION |
EP3485906A1 (en) | 2012-03-09 | 2019-05-22 | Pfizer Inc | Neisseria meningitidis compositions and methods thereof |
SA115360586B1 (en) | 2012-03-09 | 2017-04-12 | فايزر انك | Neisseria meningitidis compositions and methods thereof |
US20150079100A1 (en) | 2012-03-23 | 2015-03-19 | Bristol-Myers Squibb Company | Methods of treatments using ctla-4 antibodies |
US9592289B2 (en) | 2012-03-26 | 2017-03-14 | Sanofi | Stable IgG4 based binding agent formulations |
CN104334583A (en) | 2012-03-28 | 2015-02-04 | 弗·哈夫曼-拉罗切有限公司 | Anti-HCMV idiotypic antibodies and uses thereof |
ES2529018T3 (en) | 2012-04-02 | 2015-02-16 | F. Hoffmann-La Roche Ag | Methods and use for the evaluation of the severity of chronic obstructive pulmonary disease (COPD) |
US10130714B2 (en) | 2012-04-14 | 2018-11-20 | Academia Sinica | Enhanced anti-influenza agents conjugated with anti-inflammatory activity |
DK2838998T3 (en) | 2012-04-18 | 2018-01-15 | Cell Signaling Technology Inc | EGFR AND ROS1 IN CANCER |
GB201207297D0 (en) | 2012-04-26 | 2012-06-06 | Senzagen Ab | Analytical methods and arrays for use in the same |
US9156915B2 (en) | 2012-04-26 | 2015-10-13 | Thomas Jefferson University | Anti-GCC antibody molecules |
WO2013170051A1 (en) | 2012-05-09 | 2013-11-14 | Advanced Animal Diagnostics, Inc. | Sample cartridge and sample stage |
JP6377054B2 (en) | 2012-05-11 | 2018-08-22 | リセット セラピューティークス, インコーポレイテッド | Carbazole-containing sulfonamides as cryptochrome modulators |
US20150126388A1 (en) | 2012-05-31 | 2015-05-07 | Nanyang Technological University | Surface enhanced raman spectroscopy (sers) marker conjugates and methods of their preparation |
US10155987B2 (en) | 2012-06-12 | 2018-12-18 | Dana-Farber Cancer Institute, Inc. | Methods of predicting resistance to JAK inhibitor therapy |
US9890215B2 (en) | 2012-06-22 | 2018-02-13 | King's College London | Vista modulators for diagnosis and treatment of cancer |
WO2013192504A1 (en) | 2012-06-22 | 2013-12-27 | The Trustees Of Dartmouth College | Novel vista-ig constructs and the use of vista-ig for treatment of autoimmune, allergic and inflammatory disorders |
JP6770312B2 (en) | 2012-07-05 | 2020-10-14 | ユセベ ファルマ ソシエテ アノニム | Treatment of bone diseases |
DE102012013888A1 (en) | 2012-07-09 | 2014-05-22 | Schebo Biotech Ag | Test kit (combi rapid test) for the synchronous detection of biomarkers in stool for the detection of pathological changes in the gastrointestinal tract, especially in the intestine |
DE202012012084U1 (en) | 2012-07-09 | 2013-04-15 | Schebo Biotech Ag | Test kit (combi rapid test) for the synchronous detection of biomarkers in stool for the detection of pathological changes in the gastrointestinal tract, especially in the intestine |
US9610324B2 (en) | 2012-07-11 | 2017-04-04 | Esperion Therapeutics, Inc. | Apolipoprotein mixtures |
WO2014015217A1 (en) | 2012-07-19 | 2014-01-23 | Vertex Pharmaceuticals Incorporated | Biomarkers for hcv infected patients |
EP2687850A1 (en) | 2012-07-19 | 2014-01-22 | Roche Diagniostics GmbH | Methods of stratifying for respiratory support therapy |
WO2014018375A1 (en) | 2012-07-23 | 2014-01-30 | Xenon Pharmaceuticals Inc. | Cyp8b1 and uses thereof in therapeutic and diagnostic methods |
PL2877206T3 (en) | 2012-07-27 | 2020-12-14 | Baxalta GmbH | Compositions comprising chimeric ospa molecules and methods of use thereof |
CA3163776A1 (en) | 2012-08-03 | 2014-02-06 | Foundation Medicine, Inc. | Human papilloma virus as predictor of cancer prognosis |
WO2014027959A1 (en) | 2012-08-14 | 2014-02-20 | Nanyang Technological University | Angiopoietin-like 4 antibody and a method of its use in cancer treatment |
US10036741B2 (en) | 2012-08-15 | 2018-07-31 | The Procter & Gamble Company | Systems, models and methods for identifying and evaluating skin-active agents effective for treating an array of skin disorders |
JP6302909B2 (en) | 2012-08-18 | 2018-03-28 | アカデミア シニカAcademia Sinica | Cell-permeable probes for sialidase identification and imaging |
US20140056901A1 (en) | 2012-08-21 | 2014-02-27 | The Institute For Molecular Medicine | Anti-tau antibodies and compositions for and methods of making and using in treatment, diagnosis and monitoring of tauopathies |
JP6368308B2 (en) | 2012-09-07 | 2018-08-01 | トラスティーズ・オブ・ダートマス・カレッジ | VISTA modulators for cancer diagnosis and treatment |
CN104662043B (en) | 2012-09-10 | 2019-10-18 | 明斯特大学 | For preventing, treating and diagnosing the method and compound of inflammatory conditions |
US10288626B2 (en) | 2012-09-14 | 2019-05-14 | University Of Kentucky Research Foundation | Secreted tumor-associated cytochrome as a blood-based biomarker for cancer |
US9618514B2 (en) | 2012-09-17 | 2017-04-11 | Agios Pharmaceuticals, Inc | Methods of evaluating patients using E-cadherin and vimentin |
WO2014047285A1 (en) | 2012-09-19 | 2014-03-27 | Paraskevi Giannakakou | Identifying taxane sensitivity in prostate cancer patients |
US11105809B2 (en) | 2012-10-09 | 2021-08-31 | Ramot At Tel-Aviv University Ltd. | Methods and kits for predicting prognosis of cancer using soluble mortalin in blood |
JP6348115B2 (en) | 2012-10-26 | 2018-06-27 | ザ ユニバーシティー オブ クイーンズランド | Use of endocytosis inhibitors and antibodies for cancer therapy |
KR20150087270A (en) | 2012-11-05 | 2015-07-29 | 프로나이 테라퓨틱스, 인코포레이티드 | Methods of using biomarkers for the treatment of cancer by modulation of bcl2 expression |
CA2890207A1 (en) | 2012-11-05 | 2014-05-08 | Foundation Medicine, Inc. | Novel ntrk1 fusion molecules and uses thereof |
ES2761951T3 (en) | 2012-11-21 | 2020-05-21 | Agios Pharmaceuticals Inc | Glutaminase inhibitors and methods of use |
UY35148A (en) | 2012-11-21 | 2014-05-30 | Amgen Inc | HETERODIMERIC IMMUNOGLOBULINS |
WO2014079011A1 (en) | 2012-11-22 | 2014-05-30 | Agios Pharmaceuticals, Inc. | Heterocyclic compounds for inhibiting glutaminase and their methods of use |
CA2891514C (en) | 2012-12-07 | 2020-08-25 | Glycomimetics, Inc. | Compounds, compositions and methods using e-selectin antagonists for mobilization of hematopoietic cells |
GB201223053D0 (en) | 2012-12-20 | 2013-02-06 | Medical Res Council | Receptor |
EP2938633B1 (en) | 2012-12-28 | 2018-02-07 | Precision Biologics, Inc. | Humanized monoclonal antibodies and methods of use for the diagnosis and treatment of colon and pancreas cancer |
ES2761575T3 (en) * | 2013-01-02 | 2020-05-20 | Qiagen Sciences Llc | Methods to predict the time to delivery in a pregnant woman |
KR102565827B1 (en) | 2013-01-09 | 2023-08-11 | 유니버시티 오브 마이애미 | Compositions and methods for the regulation of t regulatory cells using tl1a-ig fusion protein |
EP2945652B1 (en) | 2013-01-18 | 2021-07-07 | Foundation Medicine, Inc. | Methods of treating cholangiocarcinoma |
WO2014122166A1 (en) | 2013-02-06 | 2014-08-14 | Pieris Ag | Novel lipocalin-mutein assays for measuring hepcidin concentration |
WO2014136064A2 (en) | 2013-03-08 | 2014-09-12 | Pfizer Inc. | Immunogenic fusion polypeptides |
US9052314B2 (en) | 2013-03-14 | 2015-06-09 | Silver Lake Research Corporation | Biomarkers for detecting the presence of bacteria |
WO2014152656A1 (en) | 2013-03-14 | 2014-09-25 | Cheng Kasing | Test strip housing system |
US9302005B2 (en) | 2013-03-14 | 2016-04-05 | Mayo Foundation For Medical Education And Research | Methods and materials for treating cancer |
US9151747B1 (en) | 2013-03-14 | 2015-10-06 | Mercyhurst University | Sucralose antibody and immunoassay |
WO2014145797A2 (en) | 2013-03-15 | 2014-09-18 | Adair Charles | Method for treating eclampsia and preeclampsia |
PT2970980T (en) | 2013-03-15 | 2018-11-19 | Janssen Biotech Inc | Manufacturing methods to control c-terminal lysine, galactose and sialic acid content in recombinant proteins |
CA2903968A1 (en) | 2013-03-15 | 2014-09-18 | Westfaelische Wilhelms-Universitaet Muenster | Detection of acute renal allograft rejection |
EP2976094B1 (en) | 2013-03-21 | 2019-08-28 | The Regents of The University of Michigan | Methods of treating metabolic disorders |
GB201305940D0 (en) | 2013-04-02 | 2013-05-15 | Immunovia Ab | Methods and arrays for use in the same |
GB201306147D0 (en) | 2013-04-05 | 2013-05-22 | Univ Ha Il | Novel biomarker signature and uses thereof |
AR096203A1 (en) | 2013-05-06 | 2015-12-16 | Alnylam Pharmaceuticals Inc | DOSAGES AND METHODS FOR MANAGING NUCLEIC ACID MOLECULES FORMULATED IN LIPIDS |
EP3004334A4 (en) | 2013-05-28 | 2016-12-21 | Biogen Ma Inc | Method of assessing risk of pml |
WO2014195852A1 (en) | 2013-06-03 | 2014-12-11 | Glaxosmithkline Intellectual Property (No.2) Limited | Combinations of an anti-pd-l1 antibody and a mek inhibitor and/or a braf inhibitor |
EP3004882B1 (en) * | 2013-06-06 | 2018-03-21 | Koninklijke Philips N.V. | Reagents, methods and devices to prevent aggregation in particle based tests for the detection of multimeric target molecules |
US10086054B2 (en) | 2013-06-26 | 2018-10-02 | Academia Sinica | RM2 antigens and use thereof |
WO2014210564A1 (en) | 2013-06-27 | 2014-12-31 | Academia Sinica | Glycan conjugates and use thereof |
US10364277B2 (en) | 2013-07-01 | 2019-07-30 | Newsouth Innovations Pty Limited | Diagnosis and treatment of autoimmune diseases |
EP3022303B1 (en) | 2013-07-17 | 2023-11-01 | Foundation Medicine, Inc. | Methods of treating urothelial carcinomas |
US9770461B2 (en) | 2013-08-02 | 2017-09-26 | California Institute Of Technology | Tailored glycopolymers as anticoagulant heparin mimetics |
US10227370B2 (en) | 2013-08-02 | 2019-03-12 | California Institute Of Technology | Heparan sulfate/heparin mimetics with anti-chemokine and anti-inflammatory activity |
EP3674422A3 (en) | 2013-09-06 | 2020-09-16 | Labrador Diagnostics LLC | Systems and methods for detecting infectious diseases |
CA2923579C (en) | 2013-09-06 | 2023-09-05 | Academia Sinica | Human inkt cell activation using glycolipids with altered glycosyl groups |
KR20210002757A (en) | 2013-09-08 | 2021-01-08 | 화이자 인코포레이티드 | Neisseria meningitidis compositions and methods thereof |
WO2015036956A1 (en) | 2013-09-12 | 2015-03-19 | Institut National De La Sante Et De La Recherche Medicale | Method for in vitro quantifying allo-antibodies, auto-antibodies and/or therapeutic antibodies |
CN112552401B (en) | 2013-09-13 | 2023-08-25 | 广州百济神州生物制药有限公司 | anti-PD 1 antibodies and their use as therapeutic and diagnostic agents |
JP6546178B2 (en) | 2013-09-13 | 2019-07-17 | ジェネンテック, インコーポレイテッド | Compositions and methods for detecting and quantifying host cell proteins and recombinant polypeptide products in cell lines |
MY176026A (en) | 2013-09-13 | 2020-07-22 | Genentech Inc | Methods and composions comprising purified recombinant polypeptides |
WO2015050959A1 (en) | 2013-10-01 | 2015-04-09 | Yale University | Anti-kit antibodies and methods of use thereof |
WO2015050663A1 (en) | 2013-10-01 | 2015-04-09 | Mayo Foundation For Medical Education And Research | Methods for treating cancer in patients with elevated levels of bim |
WO2015051302A1 (en) | 2013-10-04 | 2015-04-09 | Aptose Biosciences Inc. | Compositions and methods for treating cancers |
WO2015063604A2 (en) | 2013-11-01 | 2015-05-07 | Imberti Luisa | BIOMARKERS PREDICTIVE OF THERAPEUTIC RESPONSIVENESS TO IFNβ AND USES THEREOF |
GB201319878D0 (en) | 2013-11-11 | 2013-12-25 | Immunovia Ab | Method, Array and use thereof |
CN105940115B (en) | 2013-11-15 | 2021-07-06 | 巴斯德研究所 | Molecular marker of plasmodium falciparum artemisinin resistance |
EP3071217A2 (en) | 2013-11-18 | 2016-09-28 | Westfälische Wilhelms-Universität Münster | Methods, peptides and antibodies for preventing, treating and diagnosing an inflammatory condition |
NZ759287A (en) | 2013-12-02 | 2022-10-28 | Baylor College Medicine | Identification of a new polypeptide hormone for maintenance of optimal body weight and blood glucose |
US9309314B2 (en) | 2013-12-03 | 2016-04-12 | Agency For Science, Technology And Research (A*Star) | Polypeptides, nucleic acids and uses thereof |
GB201322094D0 (en) | 2013-12-13 | 2014-01-29 | Electrophoretics Ltd | Methods and compositions relating to alzheimers disease |
EP3083670A2 (en) | 2013-12-17 | 2016-10-26 | Westfälische Wilhelms-Universität Münster | Means and methods for treating a pruritus-like skin-disease |
EP2960252A1 (en) | 2014-06-26 | 2015-12-30 | Institut Pasteur | Phospholipase for treatment of immunosuppression |
US11014987B2 (en) | 2013-12-24 | 2021-05-25 | Janssen Pharmaceutics Nv | Anti-vista antibodies and fragments, uses thereof, and methods of identifying same |
SI3712174T1 (en) | 2013-12-24 | 2022-06-30 | Janssen Pharmaceutica Nv | Anti-vista antibodies and fragments |
WO2015175340A1 (en) | 2014-05-13 | 2015-11-19 | Bavarian Nordic, Inc. | Combination therapy for treating cancer with a poxvirus expressing a tumor antigen and a monoclonal antibody against tim-3 |
EP3091982B1 (en) | 2014-01-09 | 2019-04-17 | Intra-Cellular Therapies, Inc. | Organic compounds |
EP4101461A1 (en) | 2014-01-09 | 2022-12-14 | Hadasit Medical Research Services and Development Ltd. | Improved cell compositions and methods for cancer therapy |
CA2937123A1 (en) | 2014-01-16 | 2015-07-23 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
US10150818B2 (en) | 2014-01-16 | 2018-12-11 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
CA2936805C (en) | 2014-01-17 | 2024-02-20 | Minomic International Ltd. | Cell surface prostate cancer antigen for diagnosis |
US20160030459A1 (en) | 2014-01-21 | 2016-02-04 | Immune Design Corp. | Compositions and methods for treating allergic conditions |
AU2015218365A1 (en) | 2014-02-14 | 2016-09-01 | Immune Design Corp. | Immunotherapy of cancer through combination of local and systemic immune stimulation |
GB201403115D0 (en) | 2014-02-21 | 2014-04-09 | Qbd Qs Ip Ltd | Red blood cell detection |
CA2940422A1 (en) | 2014-02-24 | 2015-08-27 | Children's Hospital Medical Center | Methods and compositions for personalized pain management |
US10955422B2 (en) | 2014-02-27 | 2021-03-23 | Biogen Ma, Inc. | Method of assessing risk of PML |
WO2015143340A1 (en) | 2014-03-21 | 2015-09-24 | Agios Pharmaceuticals, Inc. | Compounds and their methods of use |
CN106415244B (en) | 2014-03-27 | 2020-04-24 | 中央研究院 | Reactive marker compounds and uses thereof |
RU2016137179A (en) | 2014-03-31 | 2018-05-07 | Дебиофарм Интернэшнл Са | FGFR HYBRID PROTEINS |
CA2943821A1 (en) | 2014-04-02 | 2015-10-08 | Crescendo Bioscience | Biomarkers and methods for measuring and monitoring juvenile idiopathic arthritis activity |
TWI690521B (en) | 2014-04-07 | 2020-04-11 | 美商同步製藥公司 | Carbazole-containing amides, carbamates, and ureas as cryptochrome modulators |
US9176113B1 (en) | 2014-04-11 | 2015-11-03 | Synapdx Corporation | Methods and systems for determining autism spectrum disorder risk |
EP3134439B1 (en) | 2014-04-21 | 2018-12-26 | Millennium Pharmaceuticals, Inc. | Anti-psyk antibody molecules and use of same for syk-targeted therapy |
US10247729B2 (en) | 2014-05-05 | 2019-04-02 | Microbplex, Inc. | Media elaborated with newly synthesized antibodies (MENSA) and uses thereof |
WO2015169884A2 (en) | 2014-05-07 | 2015-11-12 | Westfaelische Wilhelms-Universitaet Muenster | Compounds and methods for the treatment of itch |
WO2015172083A1 (en) | 2014-05-08 | 2015-11-12 | Biogen Ma Inc. | Dimethylfumarate and prodrugs for treatment of multiple sclerosis |
US20170269075A1 (en) | 2014-05-12 | 2017-09-21 | Biogen Ma Inc. | Biomarkers predictive of lupus progression and uses thereof |
WO2015179654A1 (en) | 2014-05-22 | 2015-11-26 | Mayo Foundation For Medical Education And Research | Distinguishing antagonistic and agonistic anti b7-h1 antibodies |
EP3149036A4 (en) | 2014-05-27 | 2017-12-27 | Academia Sinica | Anti-cd20 glycoantibodies and uses thereof |
TWI717319B (en) | 2014-05-27 | 2021-02-01 | 中央研究院 | Fucosidase from bacteroides and methods using the same |
EP4116329A1 (en) | 2014-05-27 | 2023-01-11 | Academia Sinica | Anti-her2 glycoantibodies and uses thereof |
US10118969B2 (en) | 2014-05-27 | 2018-11-06 | Academia Sinica | Compositions and methods relating to universal glycoforms for enhanced antibody efficacy |
TWI732738B (en) | 2014-05-28 | 2021-07-11 | 中央研究院 | Anti-tnf-alpha glycoantibodies and uses thereof |
GB201410226D0 (en) | 2014-06-09 | 2014-07-23 | Immunovia Ab | Methods and arrays for use in the same |
CA2950771A1 (en) | 2014-06-10 | 2015-12-17 | Crescendo Bioscience | Biomarkers and methods for measuring and monitoring axial spondyloarthritis disease activity |
WO2015191881A2 (en) | 2014-06-11 | 2015-12-17 | Green Kathy A | Use of vista agonists and antagonists to suppress or enhance humoral immunity |
SG11201610630RA (en) | 2014-06-25 | 2017-01-27 | Tel Hashomer Medical Res Infrastructure & Services Ltd | Identification of cancer stem cell markers and use of same for diagnosis and treatment |
FR3023003B1 (en) | 2014-06-27 | 2016-07-15 | Bio-Rad Innovations | SYNERGISTIC COMBINATION OF BIOMARKERS FOR THE DETECTION AND EVALUATION OF A HEPATIC FIBROSIS |
AU2015289773A1 (en) | 2014-07-15 | 2017-02-02 | Immune Design Corp. | Prime-boost regimens with a TLR4 agonist adjuvant and a lentiviral vector |
US10517875B2 (en) | 2014-07-23 | 2019-12-31 | Mayo Foundation for Medical Engineering and Research | Targeting DNA-PKcs and B7-H1 to treat cancer |
CN113846062A (en) | 2014-07-25 | 2021-12-28 | 赛拉福柯蒂斯公司 | Lentiviral vectors for regulated expression of chimeric antigen receptor molecules |
EP3177738B1 (en) | 2014-08-08 | 2019-10-09 | Children's Hospital Medical Center | Diagnostic method for distinguishing forms of esophageal eosinophilia |
EP3180621B1 (en) | 2014-08-14 | 2020-04-01 | Memed Diagnostics Ltd. | Computational analysis of biological data using manifold and a hyperplane |
WO2016026978A1 (en) | 2014-08-22 | 2016-02-25 | Universite Nice Sophia Antipolis | Methods and pharmaceutical compositions for treating drug addiction |
CA2960712A1 (en) | 2014-09-08 | 2016-03-17 | Academia Sinica | Human inkt cell activation using glycolipids |
EP3204777A1 (en) | 2014-10-08 | 2017-08-16 | Novartis AG | Biomarkers predictive of therapeutic responsiveness to chimeric antigen receptor therapy and uses thereof |
JP6767374B2 (en) | 2014-10-20 | 2020-10-14 | ジェン−プローブ・インコーポレーテッド | Red blood cell lysing solution |
US9107906B1 (en) | 2014-10-28 | 2015-08-18 | Adma Biologics, Inc. | Compositions and methods for the treatment of immunodeficiency |
EP3221340A1 (en) | 2014-11-19 | 2017-09-27 | Koninklijke Philips N.V. | Diagnostic method employing hnl |
AU2015357463B2 (en) | 2014-12-05 | 2021-10-07 | Immunext, Inc. | Identification of VSIG8 as the putative vista receptor and its use thereof to produce vista/VSIG8 modulators |
MA41142A (en) | 2014-12-12 | 2017-10-17 | Amgen Inc | ANTI-SCLEROSTINE ANTIBODIES AND THE USE OF THEM TO TREAT BONE CONDITIONS AS PART OF THE TREATMENT PROTOCOL |
US9975965B2 (en) | 2015-01-16 | 2018-05-22 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
US10495645B2 (en) | 2015-01-16 | 2019-12-03 | Academia Sinica | Cancer markers and methods of use thereof |
CA2972072A1 (en) | 2015-01-24 | 2016-07-28 | Academia Sinica | Novel glycan conjugates and methods of use thereof |
WO2016123329A2 (en) | 2015-01-28 | 2016-08-04 | Genentech, Inc. | Gene expression markers and treatment of multiple sclerosis |
MX2017010705A (en) | 2015-02-19 | 2017-12-04 | Pfizer | Neisseria meningitidis compositions and methods thereof. |
US10073098B2 (en) | 2015-03-06 | 2018-09-11 | Genentech, Inc. | Ultrapurified DsbA and DsbC and methods of making and using the same |
WO2016149537A1 (en) | 2015-03-17 | 2016-09-22 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Bank vole prion protein as a broad-spectrum substrate for rt-quic-based detection and discrimination of prion strains |
GB201504432D0 (en) | 2015-03-17 | 2015-04-29 | Electrophoretics Ltd | Materials and methods for diagnosis and treatment of alzheimers disease |
US11279768B1 (en) | 2015-04-03 | 2022-03-22 | Precision Biologics, Inc. | Anti-cancer antibodies, combination therapies, and uses thereof |
US9758575B2 (en) | 2015-04-06 | 2017-09-12 | Yung Shin Pharmaceutical Industrial Co. Ltd. | Antibodies which specifically bind to canine vascular endothelial growth factor and uses thereof |
EP3285811A1 (en) | 2015-04-21 | 2018-02-28 | Institut Gustave Roussy | Therapeutic methods, products and compositions inhibiting znf555 |
SG11201708334RA (en) | 2015-05-04 | 2017-11-29 | Pieris Pharmaceuticals Gmbh | Anti-cancer fusion polypeptide |
WO2016178154A1 (en) | 2015-05-04 | 2016-11-10 | Westfälische Wilhelms-Universität Münster | Means and methods for diagnosing and treating inflammatory disorders |
EP3294280A1 (en) | 2015-05-11 | 2018-03-21 | Yeda Research and Development Co., Ltd. | Citrin inhibitors for the treatment of cancer |
CN107614525B (en) | 2015-05-22 | 2021-07-06 | 华辉安健(北京)生物科技有限公司 | Anti pre-S1 HBV antibodies |
NL2014935B1 (en) | 2015-06-08 | 2017-02-03 | Applied Immune Tech Ltd | T cell receptor like antibodies having fine specificity. |
CA2990360C (en) | 2015-06-24 | 2024-02-13 | Janssen Pharmaceutica Nv | Anti-vista antibodies and fragments |
HUE056054T2 (en) | 2015-08-25 | 2022-02-28 | Prothena Biosciences Ltd | Methods for detecting phosphorylated alpha-synuclein |
WO2017040342A1 (en) | 2015-08-28 | 2017-03-09 | Genentech, Inc. | Anti-hypusine antibodies and uses thereof |
US11747346B2 (en) | 2015-09-03 | 2023-09-05 | Novartis Ag | Biomarkers predictive of cytokine release syndrome |
GB201516801D0 (en) | 2015-09-22 | 2015-11-04 | Immunovia Ab | Method, array and use thereof |
RU2763916C2 (en) | 2015-09-23 | 2022-01-11 | Дженентек, Инк. | Optimized options of anti-vegf antibodies |
EP3356832A4 (en) | 2015-09-29 | 2019-06-19 | Sasso, Eric | Biomarkers and methods for assessing psoriatic arthritis disease activity |
WO2017058999A2 (en) | 2015-09-29 | 2017-04-06 | Crescendo Bioscience | Biomarkers and methods for assessing response to inflammatory disease therapy withdrawal |
CA3000697A1 (en) | 2015-10-01 | 2017-04-06 | Amgen Inc. | Treatment of bile acid disorders |
AU2016340125B2 (en) | 2015-10-15 | 2021-12-09 | Inbios International, Inc. Disabled | Multiplexed lateral flow assay systems and methods for their use |
IL295097A (en) | 2015-10-30 | 2022-09-01 | Genentech Inc | Anti-htra1 antibodies and methods of use thereof |
AU2016343937B2 (en) | 2015-10-30 | 2023-01-19 | Exact Sciences Corporation | Multiplex amplification detection assay and isolation and detection of DNA from plasma |
WO2017075045A2 (en) | 2015-10-30 | 2017-05-04 | Mayo Foundation For Medical Education And Research | Antibodies to b7-h1 |
EP3370724A2 (en) | 2015-11-03 | 2018-09-12 | GlycoMimetics, Inc. | Antibodies for targeting cancer stem cells and treating aggressive cancers |
CN108350077A (en) | 2015-11-03 | 2018-07-31 | 糖模拟物有限公司 | Generate monoclonal antibody, the method and composition of candidate stem cell and the method using the antibody and candidate stem cell |
GB201520258D0 (en) | 2015-11-17 | 2015-12-30 | Academisch Ziekenhuis Leiden | Modulation of ciliogenesis |
US10816549B2 (en) | 2015-12-15 | 2020-10-27 | Case Western Reserve University | Epithelial cancer evaluation using beta defensin |
WO2017123401A1 (en) | 2016-01-13 | 2017-07-20 | Children's Hospital Medical Center | Compositions and methods for treating allergic inflammatory conditions |
EP3410849B1 (en) | 2016-02-05 | 2023-07-05 | Institut Pasteur | Use of inhibitors of adam12 as adjuvants in tumor therapies |
JP2019509993A (en) | 2016-02-12 | 2019-04-11 | ヤンセン ファーマシューティカ エヌブイ | Anti-VISTA (B7H5) antibody |
US11725247B2 (en) | 2016-02-29 | 2023-08-15 | Foundation Medicine, Inc. | Methods of treating cancer |
CA3016170A1 (en) | 2016-03-08 | 2017-09-14 | Academia Sinica | Methods for modular synthesis of n-glycans and arrays thereof |
GB201604124D0 (en) | 2016-03-10 | 2016-04-27 | Ucb Biopharma Sprl | Pharmaceutical formulation |
CN109715802A (en) | 2016-03-18 | 2019-05-03 | 卡里斯科学公司 | Oligonucleotide probe and application thereof |
GB201700138D0 (en) | 2017-01-05 | 2017-02-22 | Senzagen Ab | Analytical methods and arrays for use in the same |
ES2934349T3 (en) | 2016-03-23 | 2023-02-21 | Senzagen Ab | Analysis procedures and matrices for their use in them |
WO2017175058A1 (en) | 2016-04-07 | 2017-10-12 | Janssen Pharmaceutica Nv | Anti-vista antibodies and fragments, uses thereof, and methods of identifying same |
CA3020848A1 (en) | 2016-04-15 | 2017-10-19 | Janssen Pharmaceuticals, Inc. | Anti-human vista antibodies and use thereof |
EP3446127A4 (en) | 2016-04-20 | 2020-01-22 | Crescendo Bioscience, Inc. | Biomarkers and methods for assessing response to inflammatory disease therapy |
DE202017007130U1 (en) | 2016-04-27 | 2019-08-29 | Gen-Probe Inc. | Lysis reagent for blood cells |
GB201608192D0 (en) | 2016-05-10 | 2016-06-22 | Immunovia Ab | Method, array and use thereof |
WO2017205686A1 (en) | 2016-05-25 | 2017-11-30 | Caris Science, Inc. | Oligonucleotide probes and uses thereof |
GB201609950D0 (en) | 2016-06-07 | 2016-07-20 | Immunovia Ab | Biomarkers signatures and uses thereof |
GB201609951D0 (en) | 2016-06-07 | 2016-07-20 | Immunovia Ab | Biomarkers signatures and uses thereof |
EP3264087B1 (en) | 2016-06-27 | 2020-04-22 | Chimera Biotec GmbH | Method and device for quantification of target molecules |
US11125744B2 (en) | 2016-06-30 | 2021-09-21 | Siemens Healthineers Nederland B.V. | Device, system and method for detecting an analyte in a body fluid sample containing a plurality of cells |
US11340223B2 (en) | 2016-07-10 | 2022-05-24 | Memed Diagnostics Ltd. | Early diagnosis of infections |
EP3482200B1 (en) | 2016-07-10 | 2022-05-04 | Memed Diagnostics Ltd. | Protein signatures for distinguishing between bacterial and viral infections |
US11832801B2 (en) | 2016-07-11 | 2023-12-05 | Arizona Board Of Regents On Behalf Of Arizona State University | Sweat as a biofluid for analysis and disease identification |
WO2018029690A1 (en) | 2016-08-10 | 2018-02-15 | Memed Diagnostics Ltd. | System and method for analysis of biological data |
EP3497237B1 (en) | 2016-08-10 | 2022-05-04 | Institut Pasteur | Methods and reagents for detecting piperaquine-resistant plasmodium falciparum malaria |
TWI739887B (en) | 2016-08-19 | 2021-09-21 | 英屬開曼群島商百濟神州有限公司 | Treatment cancers using a combination comprising btk inhibitors |
CA3034057A1 (en) | 2016-08-22 | 2018-03-01 | CHO Pharma Inc. | Antibodies, binding fragments, and methods of use |
JP6968872B2 (en) | 2016-08-26 | 2021-11-17 | ベイジーン リミテッド | Anti-Tim-3 antibody |
WO2018045162A1 (en) | 2016-09-01 | 2018-03-08 | Biogen Ma Inc. | Biomarkers predictive of primary progressive multiple sclerosis and uses thereof |
JP2020501506A (en) | 2016-09-07 | 2020-01-23 | イッサム リサーチ デベロップメント カンパニー オブ ザ ヘブリュー ユニバーシティー オブ エルサレム エルティーディー. | Anti-NKp46 antibody and therapeutic use thereof |
WO2018075408A1 (en) | 2016-10-17 | 2018-04-26 | Alexion Pharmaceuticals, Inc. | Methods of treating acute myeloid leukemia (aml) with combinations of anti-cd200 antibodies, cytarabine, and daunorubicin |
WO2018102594A1 (en) | 2016-12-01 | 2018-06-07 | Alexion Pharmaceuticals, Inc. | Methods of treating solid tumors with anti-cd200 antibodies |
US10935555B2 (en) | 2016-12-22 | 2021-03-02 | Qiagen Sciences, Llc | Determining candidate for induction of labor |
US10656164B2 (en) | 2016-12-22 | 2020-05-19 | Qiagen Sciences, Llc | Screening asymptomatic pregnant woman for preterm birth |
WO2018136553A1 (en) | 2017-01-18 | 2018-07-26 | Genentech, Inc. | Idiotypic antibodies against anti-pd-l1 antibodies and uses thereof |
EP3571309A4 (en) | 2017-01-20 | 2020-11-25 | Children's Hospital Medical Center | Methods and compositions relating to oprm1 dna methylation for personalized pain management |
IL303108B1 (en) | 2017-01-31 | 2024-03-01 | Pfizer | Neisseria meningitidis compositions and methods thereof |
GB201701572D0 (en) | 2017-01-31 | 2017-03-15 | Immunovia Ab | Methods, arrays and uses thereof |
WO2018148180A2 (en) | 2017-02-07 | 2018-08-16 | Immune Design Corp. | Materials and methods for identifying and treating cancer patients |
US11061026B2 (en) * | 2017-02-17 | 2021-07-13 | MFB Fertility, Inc. | System of evaluating corpus luteum function by recurrently evaluating progesterone non-serum bodily fluids on multiple days |
US10259865B2 (en) | 2017-03-15 | 2019-04-16 | Adma Biologics, Inc. | Anti-pneumococcal hyperimmune globulin for the treatment and prevention of pneumococcal infection |
GB201706464D0 (en) | 2017-04-24 | 2017-06-07 | Senzagen Ab | Analytical methods and arrays for use in the same |
AU2018258263A1 (en) | 2017-04-24 | 2019-10-24 | Genentech, Inc. | ErbB2/Her2 mutations in the transmembrane or juxtamembrane domain |
WO2018202471A1 (en) | 2017-05-02 | 2018-11-08 | Bayer Aktiengesellschaft | Tmem16a modulation for diagnostic or therapeutic use in pulmonary hypertension (ph) |
JP7470268B2 (en) | 2017-09-14 | 2024-04-18 | ラボラトリー・コーポレイション・オブ・アメリカ・ホールディングス | Biomarkers and methods for assessing risk of myocardial infarction and serious infections in patients with rheumatoid arthritis - Patents.com |
GB201715445D0 (en) | 2017-09-25 | 2017-11-08 | Senzagen Ab | Novel cell line and uses thereof |
WO2019067403A2 (en) | 2017-09-26 | 2019-04-04 | Sanford Burnham Prebys Medical Discovery Institute | Compositions and methods for assessing painful demyelinating and nondemyelinating diseases |
US11761963B2 (en) | 2017-09-27 | 2023-09-19 | Alexion Pharmaceuticals, Inc. | Biomarker signature for predicting tumor response to anti-CD200 therapy |
EP3697809A1 (en) | 2017-10-20 | 2020-08-26 | Institut Curie | Dap10/12 based cars adapted for rush |
EP3704153A2 (en) | 2017-11-02 | 2020-09-09 | Bayer Aktiengesellschaft | Bispecific antibodies binding alk-1 and bmpr-2 |
AU2018364630A1 (en) | 2017-11-09 | 2020-05-21 | Pinteon Therapeutics Inc. | Methods and compositions for the generation and use of humanized conformation-specific phosphorylated tau antibodies |
WO2019126133A1 (en) | 2017-12-20 | 2019-06-27 | Alexion Pharmaceuticals, Inc. | Liquid formulations of anti-cd200 antibodies |
US11802154B2 (en) | 2017-12-20 | 2023-10-31 | Alexion Pharmaceuticals, Inc. | Humanized anti-CD200 antibodies and uses thereof |
EP3727459A2 (en) | 2017-12-21 | 2020-10-28 | Friedrich-Alexander-Universität Erlangen-Nürnberg | Immunotoxin conjugates for use in therapy |
US11572405B2 (en) | 2018-01-12 | 2023-02-07 | Bristol-Myers Squibb Company | Combination therapy with anti-IL-8 antibodies and anti-PD-1 antibodies for treating cancer |
US11834487B2 (en) | 2018-02-12 | 2023-12-05 | Hadasit Medical Research Services & Development Ltd. | Modulation of SLAMF6 splice variants for cancer therapy |
US11859250B1 (en) | 2018-02-23 | 2024-01-02 | Children's Hospital Medical Center | Methods for treating eosinophilic esophagitis |
EP3530282A1 (en) | 2018-02-27 | 2019-08-28 | Diaccurate | Therapeutic methods |
EP3775900A1 (en) | 2018-03-26 | 2021-02-17 | Alexion Pharmaceuticals, Inc. | High throughput method for measuring the protease activity of complement c3 convertase |
CA3093457A1 (en) | 2018-03-30 | 2019-10-03 | Amgen Inc. | C-terminal antibody variants |
CN112334485A (en) | 2018-04-06 | 2021-02-05 | 百进生物科技公司 | Anti-tetraspanin 33agents and compositions thereof and methods of making and using |
WO2019237119A1 (en) | 2018-06-08 | 2019-12-12 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | New compositions and detection methods for onchocerca volvulus infection |
AU2019310039A1 (en) | 2018-07-23 | 2021-02-18 | Enclear Therapies, Inc. | Methods of treating neurological disorders |
CN113164557A (en) | 2018-07-23 | 2021-07-23 | 因柯利尔疗法公司 | Methods of treating neurological disorders |
WO2020043693A1 (en) | 2018-08-29 | 2020-03-05 | Westfälische Wilhelms-Universität Münster | Diagnosis of multiple sclerosis |
JP2022501374A (en) | 2018-09-21 | 2022-01-06 | プレジデント アンド フェローズ オブ ハーバード カレッジ | Methods and Compositions for Treating Diabetes, as well as Methods for Concentrating mRNA Encoding Secretory Proteins |
EP3856343A1 (en) | 2018-09-25 | 2021-08-04 | Biolegend, Inc. | Anti-tlr9 agents and compositions and methods for making and using the same |
DE102018124022A1 (en) | 2018-09-28 | 2020-04-02 | Rheinisch-Westfälische Technische Hochschule (Rwth) Aachen | HYALURONIC ACID STABILIZER |
CA3113818A1 (en) | 2018-10-05 | 2020-04-09 | Bavarian Nordic A/S | Combination therapy for treating cancer with an intravenous administration of a recombinant mva and an immune checkpoint antagonist or agonist |
WO2020077286A1 (en) | 2018-10-12 | 2020-04-16 | Quidel Corporation | Extraction reagent for use in an assay for detection of group a streptococcus |
WO2020081493A1 (en) | 2018-10-16 | 2020-04-23 | Molecular Templates, Inc. | Pd-l1 binding proteins |
BR112021009856A8 (en) | 2018-11-20 | 2021-09-08 | Bavarian Nordic As | Therapy for treating cancer with an intratumoral and/or intravenous administration of a recombinant mva encoding 4-1bbl (cd137l) and/or cd40l |
WO2020113237A1 (en) | 2018-11-30 | 2020-06-04 | Caris Mpi, Inc. | Next-generation molecular profiling |
US20220098310A1 (en) | 2018-12-06 | 2022-03-31 | Alexion Pharmaceuticals, Inc. | Anti-alk2 antibodies and uses thereof |
JP2022515843A (en) | 2019-01-03 | 2022-02-22 | センソシェン アクティエ ボラーグ | Analytical method and array for use in it |
EP3917571A4 (en) | 2019-01-31 | 2022-10-12 | Agency For Science, Technology And Research | Cnx/erp57 inhibitor for use in the treatment or prevention of cancer |
EP3693063A1 (en) | 2019-02-06 | 2020-08-12 | Diaccurate | Methods and compositions for treating cancer |
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AU2020223293A1 (en) | 2019-02-15 | 2021-08-19 | Integral Molecular, Inc. | Claudin 6 antibodies and uses thereof |
WO2020168024A1 (en) | 2019-02-15 | 2020-08-20 | Integral Molecular, Inc. | Antibodies comprising a common light chain and uses thereof |
WO2020176637A1 (en) | 2019-02-26 | 2020-09-03 | Pantheryx, Inc. | Compositions for management of disorders of the gastrointestinal tract |
GB201904472D0 (en) | 2019-03-29 | 2019-05-15 | Immunovia Ab | Methods, arrays and uses thereof |
WO2020210634A1 (en) | 2019-04-11 | 2020-10-15 | Enclear Therapies, Inc. | Methods of amelioration of cerebrospinal fluid and devices and systems therefor |
GB2598520A (en) | 2019-05-28 | 2022-03-02 | Univ Shanghai Tech | Composition and methods to treat ectodermal dysplasia 2, Clouston type |
WO2020261281A1 (en) | 2019-06-27 | 2020-12-30 | Ramot At Tel-Aviv University Ltd. | Semaphorin 3a antibodies and uses thereof |
US20220386594A1 (en) | 2019-11-11 | 2022-12-08 | Ibi-Ag Innovative Bio Insecticides Ltd. | Insect control nanobodies and uses thereof |
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EP4069865A4 (en) | 2019-12-02 | 2023-12-20 | Caris MPI, Inc. | Pan-cancer platinum response predictor |
CN115298213A (en) | 2019-12-19 | 2022-11-04 | 奎多公司 | Monoclonal antibody fusion |
CN115427447A (en) | 2020-01-17 | 2022-12-02 | 百进生物科技公司 | anti-TLR 7 agents and compositions and methods of making and using the same |
US11815513B2 (en) | 2020-04-01 | 2023-11-14 | Institut Pasteur | Severe acute respiratory syndrome (SARS)-associated coronavirus diagnostics |
US20210311054A1 (en) | 2020-04-01 | 2021-10-07 | Institut Pasteur | Severe acute respiratory syndrome (sars) - associated coronavirus diagnostics |
WO2021209824A1 (en) | 2020-04-17 | 2021-10-21 | Institut Pasteur | Methods and products for serological analysis of sars-cov-2 infection |
EP4143237A1 (en) | 2020-04-30 | 2023-03-08 | Genentech, Inc. | Kras specific antibodies and uses thereof |
WO2021239666A1 (en) | 2020-05-26 | 2021-12-02 | Diaccurate | Therapeutic methods |
CA3182473A1 (en) | 2020-06-01 | 2021-12-09 | Genentech, Inc. | Methods for making extracellular vesicles and uses thereof |
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WO2022093640A1 (en) | 2020-10-30 | 2022-05-05 | BioLegend, Inc. | Anti-nkg2c agents and compositions and methods for making and using the same |
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WO2023144798A1 (en) | 2022-01-31 | 2023-08-03 | Genevant Sciences Gmbh | Ionizable cationic lipids for lipid nanoparticles |
WO2023192478A1 (en) | 2022-04-01 | 2023-10-05 | Bristol-Myers Squibb Company | Combination therapy with anti-il-8 antibodies and anti-pd-1 antibodies for treating cancer |
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WO2024052922A1 (en) | 2022-09-11 | 2024-03-14 | Yeda Research And Development Co. Ltd. | Anti-klk4 antibodies and uses thereof |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3654090A (en) * | 1968-09-24 | 1972-04-04 | Organon | Method for the determination of antigens and antibodies |
NL154600B (en) * | 1971-02-10 | 1977-09-15 | Organon Nv | METHOD FOR THE DETERMINATION AND DETERMINATION OF SPECIFIC BINDING PROTEINS AND THEIR CORRESPONDING BINDABLE SUBSTANCES. |
US3867517A (en) * | 1971-12-21 | 1975-02-18 | Abbott Lab | Direct radioimmunoassay for antigens and their antibodies |
US4016043A (en) * | 1975-09-04 | 1977-04-05 | Akzona Incorporated | Enzymatic immunological method for the determination of antigens and antibodies |
JPS5347518A (en) * | 1976-10-07 | 1978-04-28 | Mochida Pharm Co Ltd | Immunologically measuring method |
US4098876A (en) * | 1976-10-26 | 1978-07-04 | Corning Glass Works | Reverse sandwich immunoassay |
NL185309C (en) * | 1980-07-28 | 1990-03-01 | Akzo Nv | METHOD FOR DETERMINING ANTIGENS USING TWO OR MORE MONOCLONAL ANTIBODIES AND IMMUNE REAGENTS. |
US4376110A (en) * | 1980-08-04 | 1983-03-08 | Hybritech, Incorporated | Immunometric assays using monoclonal antibodies |
-
1980
- 1980-08-04 US US06/175,133 patent/US4376110A/en not_active Expired - Lifetime
-
1981
- 1981-07-29 IT IT8123231A patent/IT1225944B/en active
- 1981-07-31 CA CA000382964A patent/CA1281640C/en not_active Expired - Lifetime
- 1981-08-04 JP JP56122347A patent/JPS57118159A/en active Granted
- 1981-08-04 BE BE0/205580A patent/BE889855A/en not_active IP Right Cessation
-
1991
- 1991-12-09 JP JP3324583A patent/JPH0587816A/en active Pending
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JPS57118159A (en) | 1982-07-22 |
IT1225944B (en) | 1990-12-10 |
JPH0587816A (en) | 1993-04-06 |
JPH0421818B2 (en) | 1992-04-14 |
BE889855A (en) | 1982-02-04 |
IT8123231A0 (en) | 1981-07-29 |
US4376110A (en) | 1983-03-08 |
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