CA2322792A1 - Polypeptides homologous to vegf and bmp1 - Google Patents

Polypeptides homologous to vegf and bmp1 Download PDF

Info

Publication number
CA2322792A1
CA2322792A1 CA002322792A CA2322792A CA2322792A1 CA 2322792 A1 CA2322792 A1 CA 2322792A1 CA 002322792 A CA002322792 A CA 002322792A CA 2322792 A CA2322792 A CA 2322792A CA 2322792 A1 CA2322792 A1 CA 2322792A1
Authority
CA
Canada
Prior art keywords
polypeptide
vegf
cell
antibody
growth factor
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002322792A
Other languages
French (fr)
Other versions
CA2322792C (en
Inventor
Napoleone Ferrara
Sophia S. Kuo
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Genentech Inc
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US09/040,220 external-priority patent/US6391311B1/en
Application filed by Individual filed Critical Individual
Publication of CA2322792A1 publication Critical patent/CA2322792A1/en
Application granted granted Critical
Publication of CA2322792C publication Critical patent/CA2322792C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2799/00—Uses of viruses
    • C12N2799/02—Uses of viruses as vector
    • C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
    • C12N2799/026—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a baculovirus

Abstract

The present invention involves the identification and preparation of vascular endothelial growth factor-E (VEGF-E). VEGF-E is a novel polypeptide related to vascular endothelial growth factor (VEGF) and bone morphogenetic protein 1. VEGF-E has homology to VEGF including conservation of the amino acids required for activity of VEGF. VEGF-E can be useful in wound repair, as well as in the generation and regeneration of tissue.

Claims (33)

1. An isolated nucleic acid comprising a nucleotide sequence encoding a vascular endothelial cell growth factor-E (VEGF-E) polypeptide comprising amino acid residues 1 through 345 of Figure 2 (SEQ ID NO:2).
2. The nucleic acid of claim 1 comprising the sequence of nucleotides 259 through 1293 of Figure 1 (SEQ ID NO:1), or its complement.
3. An isolated nucleic acid comprising a nucleotide sequence which hybridizes under stringent conditions to the nucleotide sequence of claim 1.
4. A vector comprising the nucleic acid of claim 1.
5. A host cell comprising the nucleic acid of claim 1.
6. The host cell of claim 5, wherein said cell is a Chinese Hamster Ovary cell, an insect cell, an E. coli cell, or a yeast cell.
7. The host cell of claim 6 that is a baculovirus-infected insect cell.
8. A process for producing a vascular endothelial cell growth factor-E (VEGF-E) polypeptide comprising culturing the host cell of claim 5 under conditions suitable for expression of the VEGF-E
polypeptide and recovering the VEGF-E polypeptide from the cell culture.
9. A polypeptide produced by the process of claim 8.
10. A VEGF-E polypeptide comprising amino acid residues 1 through 345 of Figure 2 (SEQ ID NO:2).
11. A VEGF-E polypeptide selected from the group consisting of:

(a) a polypeptide comprising amino acid residues 1 through 345 of Figure 2 (SEQ ID NO:2); and (b) a polypeptide fragment of (a), wherein said fragment is biologically active.
12. A VEGF-E polypeptide encoded by the nucleotide sequence insert of ATCC deposit No. 209653.
13. A chimeric polypeptide comprising the polypeptide of claim 10 fused to a heterologous amino acid sequence.
14. The chimeric polypeptide of claim 13, wherein said heterologous amino acid sequence is an epitope tag sequence or a Fc region of an immunoglobulin.
15. A composition comprising the polypeptide of claim 10 in admixture with a carrier.
16. The composition of claim 15 comprising a therapeutically effective amount of the polypeptide, wherein the carrier is a pharmaceutically acceptable carrier.
17. A pharmaceutical product comprising:
(a) the composition of claim 15;
(b) a container containing said composition; and (c) a label affixed to said container, or a package insert included in said pharmaceutical product, referring to the use of said VEGF-E polypeptide in the treatment of a cardiovascular or endothelial disorder.
18. A method for treating a cardiovascular or endothelial disorder in a mammal comprising administering to the mammal an effective amount of the composition of claim 15.
19. The method of claim 18 wherein the disorder is cardiac hypertrophy, trauma, or a bone-related disorder.
20. The method of claim 19 wherein said cardiac hypertrophy is characterized by the presence of an elevated level of PGF2e.
21. The method of claim 19 wherein said cardiac hypertrophy has been induced by myocardial infarction.
22. The method of claim 21 wherein said VEGF-E polypeptide administration is initiated within 48 hours following myocardial infarction.
23. A method for diagnosing a disease or a susceptibility to a disease related to a mutation in a nucleic acid sequence encoding vascular endothelial cell growth factor-E (VEGF-E) comprising:
(a) isolating a nucleic acid sequence encoding VEGF-E from a sample derived from a host; and (b) determining a mutation in the nucleic acid sequence encoding VEGF-E.
24. A method of diagnosing cardiovascular and endothelial disorders in a mammal comprising detecting the level of expression of a gene encoding a vascular endothelial cell growth factor-E
(VEGF-E) polypeptide (a) in a test sample of tissue cells obtained from the mammal, and (b) in a control sample of known normal tissue cells of the same cell type, wherein a higher or lower expression level in the test sample indicates the presence of a cardiovascular or endothelial dysfunction in the mammal from which the test tissue cells were obtained.
25. A method for identifying an agonist to a vascular endothelial cell growth factor-E (VEGF-E) polypeptide comprising:
(a) contacting cells and a candidate compound under conditions that allow the polypeptide to stimulate proliferation of the cells; and (b) measuring the extent to which cell proliferation is inhibited by the compound.
26. An agonist to a VEGF-E polypeptide identified by the method of claim 25.
27. A method for identifying a compound that inhibits the expression or activity of a vascular endothelial cell growth factor-E (VEGF-E) polypeptide, comprising:

(a) contacting a candidate compound with the polypeptide under conditions and for a time sufficient to allow the compound and polypeptide to interact; and (b) measuring the extent to which the compound interacts with the polypeptide.
28. A compound identified by the method of claim 27.
29. An isolated antibody that binds a vascular endothelial cell growth factor-E (VEGF-E) polypeptide.
30. The antibody of claim 29 that is a monoclonal antibody.
31. A method for determining the presence of a vascular endothelial cell growth factor-E (VEGF-E) polypeptide comprising exposing a cell suspected of containing the VEGF-E polypeptide to the antibody of claim 29 and determining binding of said antibody to said cell.
32. A method of diagnosing cardiovascular, endothelial, or angiogenic disorders in a mammal comprising (a) contacting the antibody of claim 29 with a test sample of tissue cells obtained from the mammal, and (b) detecting the formation of a complex between the anti-VEGF-E antibody and the VEGF-E polypeptide in the test sample.
33. An article of manufacture, comprising:
a container:
a label on the container; and a composition comprising the antibody of claim 29 contained within the container; wherein the label on the container indicates instructions for using the antibody in a therapeutic method or diagnostic method.
CA2322792A 1998-03-17 1999-03-10 Polypeptides homologous to vegf and bmp1 Expired - Lifetime CA2322792C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US09/040,220 1998-03-17
US09/040,220 US6391311B1 (en) 1998-03-17 1998-03-17 Polypeptides having homology to vascular endothelial cell growth factor and bone morphogenetic protein 1
US18421698A 1998-11-02 1998-11-02
US09/184,216 1998-11-02
PCT/US1999/005190 WO1999047677A2 (en) 1998-03-17 1999-03-10 Polypeptides homologous to vegf and bmp1

Publications (2)

Publication Number Publication Date
CA2322792A1 true CA2322792A1 (en) 1999-09-23
CA2322792C CA2322792C (en) 2010-09-14

Family

ID=26716852

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2322792A Expired - Lifetime CA2322792C (en) 1998-03-17 1999-03-10 Polypeptides homologous to vegf and bmp1

Country Status (14)

Country Link
US (11) US6455283B1 (en)
EP (2) EP1064382B1 (en)
JP (3) JP4532733B2 (en)
AT (1) ATE405651T1 (en)
AU (1) AU758353B2 (en)
CA (1) CA2322792C (en)
CY (2) CY1108500T1 (en)
DE (1) DE69939374D1 (en)
DK (2) DK1064382T3 (en)
ES (2) ES2389387T3 (en)
HK (1) HK1125853A1 (en)
IL (5) IL138488A0 (en)
PT (1) PT2016951E (en)
WO (1) WO1999047677A2 (en)

Families Citing this family (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE344322T1 (en) 1998-02-13 2006-11-15 Koester Hubert USE OF RIBOZYMES TO DETERMINE THE FUNCTION OF GENES
CA2349562A1 (en) * 1998-03-06 1999-09-10 Crosscart, Inc. Soft tissue xenografts
DK1064382T3 (en) 1998-03-17 2008-12-08 Genentech Inc Homologous polypeptides for VEGF and BMP1
EP0984063A3 (en) * 1998-08-31 2000-08-16 Eli Lilly And Company VEGF Related gene and protein
US6432673B1 (en) 1998-12-07 2002-08-13 Zymogenetics, Inc. Growth factor homolog ZVEGF3
US6663870B2 (en) * 1998-12-07 2003-12-16 Zymogenetics, Inc. Methods for promoting growth of bone using zvegf3
DK1137773T3 (en) * 1998-12-07 2008-12-08 Zymogenetics Inc Liquid Factor Homolog ZVEGF3
US6783953B1 (en) 1998-12-22 2004-08-31 Janssen Pharmaceutica N.V. Vascular endothelial growth factor-X
DK1141293T3 (en) * 1998-12-22 2007-11-12 Janssen Pharmaceutica Nv Vascular endothelial growth factor-X
EP1710299A3 (en) * 1998-12-30 2007-01-10 Millennium Pharmaceuticals, Inc. Secreted proteins and nucleic acids encoding them
JP2004516227A (en) * 1999-03-08 2004-06-03 ジェネンテック・インコーポレーテッド Compositions and methods for treating immune-related diseases
AU3737500A (en) * 1999-03-12 2000-09-28 Genentech Inc. Method of preventing the death of retinal neurons and treating ocular diseases
WO2000059940A2 (en) * 1999-04-06 2000-10-12 Eli Lilly And Company Platelet-derived growth factor related gene and protein
US6630142B2 (en) * 1999-05-03 2003-10-07 Zymogenetics, Inc. Method of treating fibroproliferative disorders
EP1222279A2 (en) * 1999-10-07 2002-07-17 Curagen Corporation Growth factor polypeptides and nucleic acids encoding same
WO2001028586A1 (en) * 1999-10-21 2001-04-26 Zymogenetics, Inc. Method of treating fibrosis
US6893637B1 (en) 1999-10-21 2005-05-17 Zymogenetics, Inc. Method of treating fibrosis
AU1430601A (en) * 1999-11-02 2001-05-14 Eli Lilly And Company Methods of using lp8, a pdgf-related protein, to treat musculoskeletal disorders
EP1564292A1 (en) * 2000-01-19 2005-08-17 Parkash S. Gill Pharmaceutical compositions and methods of treatment based on VEGF antisense oligonucleotides
US7141607B1 (en) 2000-03-10 2006-11-28 Insite Vision Incorporated Methods and compositions for treating and inhibiting retinal neovascularization
WO2001072132A1 (en) * 2000-03-28 2001-10-04 Ludwig Institute For Cancer Research Non-human transgenic animals expressing platelet-derived growth factor c (pdgf-c) and uses thereof
GB0008269D0 (en) * 2000-04-05 2000-05-24 Astrazeneca Ab Combination chemotherapy
US20070111935A1 (en) * 2000-04-06 2007-05-17 Franco Wayne P Combination growth factor therapy and cell therapy for treatment of acute and chronic diseases of the organs
CA2405291A1 (en) * 2000-04-06 2001-10-18 Wayne P. Franco Methods of using growth factors for treating heart disease
US7166280B2 (en) * 2000-04-06 2007-01-23 Franco Wayne P Combination growth factor therapy and cell therapy for treatment of acute and chronic heart disease
US20050277576A1 (en) * 2000-04-06 2005-12-15 Franco Wayne P Combination growth factor therapy and cell therapy for treatment of acute and chronic diseases of the organs
ES2372809T3 (en) 2000-04-12 2012-01-26 Vib Vzw USE OF VEGF 165 AND HOMOLOGISTS TO TREAT NEURONE DISORDERS.
AU6595301A (en) * 2000-05-12 2001-11-20 Vlaams Interuniv Inst Biotech Use of inhibitors of placental growth factor for the treatment of pathological angiogenesis, pathological arteriogenesis, inflammation, tumour formation and/or vascular leakage
EP1311277A4 (en) * 2000-07-18 2004-08-25 Joslin Diabetes Center Inc Methods of modulating fibrosis
US20020091082A1 (en) * 2000-09-13 2002-07-11 Aiello Lloyd P. Methods of modulating symptoms of hypertension
JPWO2002033094A1 (en) * 2000-10-19 2004-10-21 協和醗酵工業株式会社 Antibodies that inhibit VPLF activity
AU2884102A (en) 2000-12-07 2002-06-18 Sangamo Biosciences Inc Regulation of angiogenesis with zinc finger proteins
US7067317B2 (en) 2000-12-07 2006-06-27 Sangamo Biosciences, Inc. Regulation of angiogenesis with zinc finger proteins
US20020141970A1 (en) * 2001-03-05 2002-10-03 Pettit Dean K. Stable aqueous solutions of granulocyte macrophage colony-stimulating factor
CN100391534C (en) * 2001-03-09 2008-06-04 詹森药业有限公司 Modulation of smooth muscle cell proliferation
US6913762B2 (en) * 2001-04-25 2005-07-05 Mayo Foundation For Medical Education And Research Stent having non-woven framework containing cells
US7981863B2 (en) 2001-09-19 2011-07-19 Neuronova Ab Treatment of Parkinson's disease with PDGF
US20030153524A1 (en) * 2001-12-11 2003-08-14 Hinton David R. Methods for inhibiting ocular processes
WO2003092665A2 (en) * 2002-05-02 2003-11-13 Massachusetts Eye And Ear Infirmary Ocular drug delivery systems and use thereof
WO2003094617A2 (en) * 2002-05-06 2003-11-20 Genentech, Inc. Use of vegf for treating bone defects
AU2003245935A1 (en) * 2002-06-13 2003-12-31 Novuspharma S.P.A. Derivatives of chromen-2-one as inhibitors of vegf production in mammalian cells
US20040052161A1 (en) * 2002-09-17 2004-03-18 Steven Liao Mechanical clock having wireless manipulation and adjustment function
ES2305541T3 (en) 2002-11-16 2008-11-01 Dade Behring Marburg Gmbh SCD40L, PAPP-A AND PLACENTARY GROWTH FACTOR (PIGF) AS COMBINATIONS OF BIOCHEMICAL MARKERS IN CARDIOVASCULAR DISEASES.
US20090155266A1 (en) * 2004-01-16 2009-06-18 Yale University Methods and Compositions Relating to Vascular Endothelial Growth Factor and TH2 Mediated Inflammatory Diseases
WO2005087177A2 (en) * 2004-03-05 2005-09-22 Ludwig Institute For Cancer Research Chimeric anti-vegf-d antibodies and humanized anti-vegf-d antibodies and methods of using same
WO2005087812A1 (en) * 2004-03-05 2005-09-22 Ludwig Institute For Cancer Research Multivalent antibody materials and methods for vegf/pdgf family of growth factors
US8415315B2 (en) 2004-05-06 2013-04-09 University Of Central Florida Research Foundation, Inc. Methods and compositions for inhibiting the proliferation of cancer cells
ATE478678T1 (en) 2004-05-27 2010-09-15 Vib Vzw TREATMENT OF AMYOTROHPER LATERAL SCLERosis
US20060045902A1 (en) * 2004-09-01 2006-03-02 Serbousek Jon C Polymeric wrap for in vivo delivery of osteoinductive formulations
DE102004051847B4 (en) * 2004-10-25 2008-09-18 Dade Behring Marburg Gmbh Ratio of PIGF and Flt-1 as a prognostic parameter in cardiovascular diseases
WO2006099698A2 (en) 2005-03-24 2006-09-28 Thromb-X N.V. Novel anti-plgf antibody
ES2363758T3 (en) 2005-08-15 2011-08-16 Vegenics Pty Ltd MODIFIED VEGF AND PDGF WITH IMPROVED ANGIOGENIC PROPERTIES.
EP2548579B1 (en) 2006-05-17 2015-09-02 The Ludwig Institute for Cancer Research Targeting VEGF-B regulation of fatty acid transporters to modulate human diseases
ES2354922B1 (en) 2009-09-02 2012-02-07 Fundacion Institut De Recerca De L'hospital Universitari Vall D'hebron MARKERS FOR THE SELECTION OF PERSONALIZED THERAPIES FOR THE TREATMENT OF THE C�? NCER.
TW201302793A (en) 2010-09-03 2013-01-16 Glaxo Group Ltd Novel antigen binding proteins
EA018848B1 (en) * 2010-10-20 2013-11-29 Вадим Юльевич ШАНИН Immunologically active substance, process for preparing same, bioprobe based thereon, method for diagnostics of health state using bioprobe, pharmaceutical composition and method of treatment using pharmaceutical composition
DK2785739T3 (en) 2011-12-01 2017-07-03 Thrombogenics Nv IMPROVING THE RESULT OF TREASURE CULECTOMY
MX2014012843A (en) 2012-04-24 2017-01-23 Thrombogenics Nv Anti-pdgf-c antibodies.
CN104768567B (en) * 2012-05-18 2017-07-11 奥塔哥创业有限公司 Therapeutic alliance and composition for wound healing
WO2014159813A1 (en) 2013-03-13 2014-10-02 Moderna Therapeutics, Inc. Long-lived polynucleotide molecules
CN105713095B (en) * 2016-03-14 2021-05-07 南京安吉生物科技有限公司 Multifunctional fusion polypeptide and preparation method and application thereof
KR101943081B1 (en) 2017-08-31 2019-01-29 (주)케어젠 Peptides Having Activity for Wrinkle Relief and Uses Thereof

Family Cites Families (122)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2035733A (en) * 1935-06-10 1936-03-31 Marathon Electric Mfg Fan motor mounting
US2813673A (en) * 1953-07-09 1957-11-19 Gilbert Co A C Tiltable oscillating fan
US2765977A (en) * 1954-10-13 1956-10-09 Morrison Hackley Electric ventilating fans
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
US4179337A (en) 1973-07-20 1979-12-18 Davis Frank F Non-immunogenic polypeptides
US4263428A (en) 1978-03-24 1981-04-21 The Regents Of The University Of California Bis-anthracycline nucleic acid function inhibitors and improved method for administering the same
JPS6023084B2 (en) 1979-07-11 1985-06-05 味の素株式会社 blood substitute
US4399216A (en) 1980-02-25 1983-08-16 The Trustees Of Columbia University Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
ZA811368B (en) 1980-03-24 1982-04-28 Genentech Inc Bacterial polypedtide expression employing tryptophan promoter-operator
US4376110A (en) 1980-08-04 1983-03-08 Hybritech, Incorporated Immunometric assays using monoclonal antibodies
DE3169595D1 (en) 1980-11-10 1985-05-02 Gersonde Klaus Method of preparing lipid vesicles by ultrasonic treatment, the use of this method and apparatus for its application
IE52535B1 (en) 1981-02-16 1987-12-09 Ici Plc Continuous release pharmaceutical compositions
US4873191A (en) 1981-06-12 1989-10-10 Ohio University Genetic transformation of zygotes
US4485045A (en) 1981-07-06 1984-11-27 Research Corporation Synthetic phosphatidyl cholines useful in forming liposomes
NZ201705A (en) 1981-08-31 1986-03-14 Genentech Inc Recombinant dna method for production of hepatitis b surface antigen in yeast
US4568243A (en) * 1981-10-08 1986-02-04 Barry Wright Corporation Vibration isolating seal for mounting fans and blowers
US4640835A (en) 1981-10-30 1987-02-03 Nippon Chemiphar Company, Ltd. Plasminogen activator derivatives
JPS58118008A (en) 1982-01-06 1983-07-13 Nec Corp Data processor
DE3374837D1 (en) 1982-02-17 1988-01-21 Ciba Geigy Ag Lipids in the aqueous phase
DE3218121A1 (en) 1982-05-14 1983-11-17 Leskovar, Peter, Dr.-Ing., 8000 München Pharmaceutical compositions for tumour treatment
EP0102324A3 (en) 1982-07-29 1984-11-07 Ciba-Geigy Ag Lipids and surfactants in an aqueous medium
US4870009A (en) 1982-11-22 1989-09-26 The Salk Institute For Biological Studies Method of obtaining gene product through the generation of transgenic animals
AU2353384A (en) 1983-01-19 1984-07-26 Genentech Inc. Amplification in eukaryotic host cells
US4713339A (en) 1983-01-19 1987-12-15 Genentech, Inc. Polycistronic expression vector construction
US4816567A (en) * 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4675187A (en) 1983-05-16 1987-06-23 Bristol-Myers Company BBM-1675, a new antibiotic complex
US4544545A (en) 1983-06-20 1985-10-01 Trustees University Of Massachusetts Liposomes containing modified cholesterol for organ targeting
HUT35524A (en) 1983-08-02 1985-07-29 Hoechst Ag Process for preparing pharmaceutical compositions containing regulatory /regulative/ peptides providing for the retarded release of the active substance
ATE159858T1 (en) 1983-09-26 1997-11-15 Ehrenfeld Udo AGENT AND PRODUCT FOR THE DIAGNOSIS AND THERAPY OF TUMORS AND FOR THE TREATMENT OF WEAKNESSES OF THE CELLULAR AND HUMORAL IMMUNE DEFENSE
US4615885A (en) 1983-11-01 1986-10-07 Terumo Kabushiki Kaisha Pharmaceutical composition containing urokinase
US4496689A (en) 1983-12-27 1985-01-29 Miles Laboratories, Inc. Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer
US4736866B1 (en) 1984-06-22 1988-04-12 Transgenic non-human mammals
EP0206448B1 (en) 1985-06-19 1990-11-14 Ajinomoto Co., Inc. Hemoglobin combined with a poly(alkylene oxide)
US4676980A (en) 1985-09-23 1987-06-30 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Target specific cross-linked heteroantibodies
US4703152A (en) * 1985-12-11 1987-10-27 Holmes Products Corp. Tiltable and adjustably oscillatable portable electric heater/fan
AU597574B2 (en) 1986-03-07 1990-06-07 Massachusetts Institute Of Technology Method for enhancing glycoprotein stability
US4791192A (en) 1986-06-26 1988-12-13 Takeda Chemical Industries, Ltd. Chemically modified protein with polyethyleneglycol
US5543394A (en) 1986-07-01 1996-08-06 Genetics Institute, Inc. Bone morphogenetic protein 5(BMP-5) compositions
IL83003A (en) 1986-07-01 1995-07-31 Genetics Inst Osteoinductive factors
US5013649A (en) 1986-07-01 1991-05-07 Genetics Institute, Inc. DNA sequences encoding osteoinductive products
US5631142A (en) 1986-07-01 1997-05-20 Genetics Institute, Inc. Compositions comprising bone morphogenetic protein-2 (BMP-2)
US5106748A (en) 1986-07-01 1992-04-21 Genetics Institute, Inc. Dna sequences encoding 5 proteins
US4877864A (en) 1987-03-26 1989-10-31 Genetics Institute, Inc. Osteoinductive factors
US4850804A (en) * 1986-07-07 1989-07-25 Tatung Company Of America, Inc. Portable electric fan having a universally adjustable mounting
ATE76311T1 (en) 1986-08-19 1992-06-15 Genentech Inc DEVICE AND DISPERSION FOR INTRAPULMONARY DELIVERY OF POLYPEPTIDE GROWTH SUBSTANCES AND CYTOKINES.
EP0266032A1 (en) 1986-08-29 1988-05-04 Beecham Group Plc Modified fibrinolytic enzyme
US5010182A (en) 1987-07-28 1991-04-23 Chiron Corporation DNA constructs containing a Kluyveromyces alpha factor leader sequence for directing secretion of heterologous polypeptides
EP0308936B1 (en) 1987-09-23 1994-07-06 Bristol-Myers Squibb Company Antibody heteroconjugates for the killing of HIV-infected cells
GB8724885D0 (en) 1987-10-23 1987-11-25 Binns M M Fowlpox virus promotors
US4892538A (en) 1987-11-17 1990-01-09 Brown University Research Foundation In vivo delivery of neurotransmitters by implanted, encapsulated cells
US5283187A (en) 1987-11-17 1994-02-01 Brown University Research Foundation Cell culture-containing tubular capsule produced by co-extrusion
WO1989006692A1 (en) 1988-01-12 1989-07-27 Genentech, Inc. Method of treating tumor cells by inhibiting growth factor receptor function
AU4005289A (en) 1988-08-25 1990-03-01 Smithkline Beecham Corporation Recombinant saccharomyces
US5240848A (en) 1988-11-21 1993-08-31 Monsanto Company Dna sequences encoding human vascular permeability factor having 189 amino acids
US5147638A (en) 1988-12-30 1992-09-15 Oklahoma Medical Research Foundation Inhibition of tumor growth by blockade of the protein C system
FR2646437B1 (en) 1989-04-28 1991-08-30 Transgene Sa NOVEL DNA SEQUENCES, THEIR APPLICATION AS A SEQUENCE ENCODING A SIGNAL PEPTIDE FOR THE SECRETION OF MATURE PROTEINS BY RECOMBINANT YEASTS, EXPRESSION CASSETTES, PROCESSED YEASTS AND PROCESS FOR PREPARING THE SAME
US5332671A (en) 1989-05-12 1994-07-26 Genetech, Inc. Production of vascular endothelial cell growth factor and DNA encoding same
ATE144793T1 (en) 1989-06-29 1996-11-15 Medarex Inc BISPECIFIC REAGENTS FOR AIDS THERAPY
CA2020729A1 (en) 1989-07-19 1991-01-20 Michael C. Kiefer Bone morphogenetic protein
CA2024629C (en) 1989-09-06 2001-07-24 Taiheiyo Cement Corporation Xenopus laevis bone morphogenic protein, dna encoding same and use thereof
US5013556A (en) 1989-10-20 1991-05-07 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5126323A (en) 1989-11-16 1992-06-30 Genetics Institute, Inc. Homogeneous purified k-fgf and compositions containing the same
USD325435S (en) * 1990-09-24 1992-04-14 Vornado Air Circulation Systems, Inc. Fan support base
US5206161A (en) 1991-02-01 1993-04-27 Genentech, Inc. Human plasma carboxypeptidase B
WO1992020373A1 (en) 1991-05-14 1992-11-26 Repligen Corporation Heteroconjugate antibodies for treatment of hiv infection
US5382569A (en) 1991-05-16 1995-01-17 Warner-Lambert Company Endotherlin antagonists
DE69233254T2 (en) 1991-06-14 2004-09-16 Genentech, Inc., South San Francisco Humanized Heregulin antibody
WO1993000432A1 (en) 1991-06-25 1993-01-07 Genetics Institute, Inc. Bmp-9 compositions
WO1993008829A1 (en) 1991-11-04 1993-05-13 The Regents Of The University Of California Compositions that mediate killing of hiv-infected cells
US5296769A (en) * 1992-01-24 1994-03-22 Electrolux Corporation Air guide assembly for an electric motor and methods of making
CA2134773A1 (en) 1992-06-04 1993-12-09 Robert J. Debs Methods and compositions for in vivo gene therapy
GB9214857D0 (en) 1992-07-13 1992-08-26 Medical Res Council Human nucleic acid fragments and their use
HU225646B1 (en) * 1992-10-28 2007-05-29 Genentech Inc Hvegf receptors as vascular endothelial cell growth factor antagonists
DE122004000036I1 (en) 1992-11-13 2005-07-07 Biogen Idec Inc Therapeutic use of chimeric and labeled antibodies to human B lymphocyte limited differentiation antigen for the treatment of B-cell lymphoma.
US5310313A (en) * 1992-11-23 1994-05-10 Chen C H Swinging type of electric fan
PT616812E (en) 1993-03-24 2000-04-28 Berlex Biosciences COMBINATION OF ANTI-HORMONAL COMPOUNDS AND LIGACATION MOLECULES IN CANCER TREATMENT
ATE522621T1 (en) 1993-04-05 2011-09-15 Univ Utah Res Found DIAGNOSIS AND TREATMENT OF WILLIAMS SYNDROME
US5637480A (en) 1993-05-12 1997-06-10 Genetics Institute, Inc. DNA molecules encoding bone morphogenetic protein-10
US5641756A (en) * 1993-07-27 1997-06-24 Hybridon, Inc. Modified VEGF oligonucleotides
PT716610E (en) 1993-08-26 2006-08-31 Genetics Inst Llc MORPHOGENETIC PROTEINS OF BONES FOR HUMANS TO BE USED IN NEURAL REGENERATION
US5773223A (en) 1993-09-02 1998-06-30 Chiron Corporation Endothelin B1, (ETB1) receptor polypeptide and its encoding nucleic acid methods, and uses thereof
US5399677A (en) 1993-12-07 1995-03-21 Genetics Institute, Inc. Mutants of bone morphogenetic proteins
ATE319823T1 (en) 1993-12-07 2006-03-15 Inst Genetics Llc BMP-12, BMP-13 AND TENDON-INDUCING COMPOSITIONS CONTAINING SAME
CA2188017C (en) 1994-04-25 2010-09-28 Joffre Baker Cardiotrophin and uses therefor
US5454419A (en) 1994-09-19 1995-10-03 Polybore, Inc. Method for lining a casing
US5681746A (en) 1994-12-30 1997-10-28 Chiron Viagene, Inc. Retroviral delivery of full length factor VIII
IL117645A (en) 1995-03-30 2005-08-31 Genentech Inc Vascular endothelial cell growth factor antagonists for use as medicaments in the treatment of age-related macular degeneration
US5518370A (en) * 1995-04-03 1996-05-21 Duracraft Corporation Portable electric fan with swivel mount
SG68529A1 (en) 1995-05-25 1999-11-16 Univ Singapore The use of des-aspartate-angiotensin i (agr-val-tyr-ile-his-pro-phe-his-leu) as an anti-cardiac hypertrophic agent
CN1217027A (en) * 1996-02-28 1999-05-19 拜尔公司 Parapoxviruses contg. foreign DNA, their prodn. and their use in vacciens
US6458939B1 (en) 1996-03-15 2002-10-01 Millennium Pharmaceuticals, Inc. Compositions and methods for the diagnosis, prevention, and treatment of neoplastic cell growth and proliferation
DK0912734T3 (en) * 1996-07-12 2011-02-07 Genentech Inc Chimeric heteromultimer adhesives
AU3783497A (en) 1996-08-09 1998-03-06 Yamanouchi Pharmaceutical Co., Ltd. Metabotropic glutamate receptor agonists
ES2390107T3 (en) * 1996-08-23 2012-11-06 Vegenics Pty Ltd Recombinant vascular endothelial cell growth factor-D (VEGF-D)
WO1999046281A2 (en) 1998-03-10 1999-09-16 Genentech, Inc. Novel polypeptides and nucleic acids encoding the same
IL132239A0 (en) 1997-04-07 2001-03-19 Genentech Inc Humanized antibodies and methods for forming humanized antibodies
USD398983S (en) * 1997-08-08 1998-09-29 Vornado Air Circulation Systems, Inc. Fan
US6391311B1 (en) * 1998-03-17 2002-05-21 Genentech, Inc. Polypeptides having homology to vascular endothelial cell growth factor and bone morphogenetic protein 1
WO1999037671A1 (en) 1998-01-27 1999-07-29 Eli Lilly And Company Vegf related gene and protein
DK1064382T3 (en) * 1998-03-17 2008-12-08 Genentech Inc Homologous polypeptides for VEGF and BMP1
CA2334075A1 (en) 1998-07-15 2000-01-27 Human Genome Sciences, Inc. Bone morphogenic protein
WO2000018212A2 (en) 1998-09-30 2000-04-06 Ludwig Institute For Cancer Research Platelet-derived growth factor c, dna coding therefor, and uses thereof
JP2003524383A (en) 1998-10-28 2003-08-19 インサイト・ファーマスーティカルズ・インコーポレイテッド Growth factor-related molecules
US20030027998A1 (en) * 1998-10-30 2003-02-06 Holtzman Douglas A. Novel genes encoding proteins having prognostic, diagnostic, preventive, therapeutic, and other uses
AU771751C (en) 1998-12-01 2006-04-06 Genentech Inc. Promotion or inhibition of angiogenesis and cardiovascularization
DK1137773T3 (en) 1998-12-07 2008-12-08 Zymogenetics Inc Liquid Factor Homolog ZVEGF3
US6432673B1 (en) * 1998-12-07 2002-08-13 Zymogenetics, Inc. Growth factor homolog ZVEGF3
DK1141293T3 (en) 1998-12-22 2007-11-12 Janssen Pharmaceutica Nv Vascular endothelial growth factor-X
EP1710299A3 (en) 1998-12-30 2007-01-10 Millennium Pharmaceuticals, Inc. Secreted proteins and nucleic acids encoding them
US6155782A (en) * 1999-02-01 2000-12-05 Hsu; Chin-Tien Portable fan
JP2004516227A (en) 1999-03-08 2004-06-03 ジェネンテック・インコーポレーテッド Compositions and methods for treating immune-related diseases
WO2000059940A2 (en) 1999-04-06 2000-10-12 Eli Lilly And Company Platelet-derived growth factor related gene and protein
MXPA01011158A (en) 1999-05-03 2004-06-03 Zymogenetics Inc Growth factor homolog zvegf4.
US6321034B2 (en) * 1999-12-06 2001-11-20 The Holmes Group, Inc. Pivotable heater
WO2003068155A2 (en) * 2002-02-12 2003-08-21 Vanderbilt University Inhibition of vegf receptor signaling reverses tumor resistance to radiotherapy
BR0201397B1 (en) * 2002-04-19 2011-10-18 Mounting arrangement for a cooler fan.
US6830433B2 (en) * 2002-08-05 2004-12-14 Kaz, Inc. Tower fan
US7059826B2 (en) * 2003-07-25 2006-06-13 Lasko Holdings, Inc. Multi-directional air circulating fan
US20050128698A1 (en) * 2003-12-10 2005-06-16 Huang Cheng Y. Cooling fan
WO2005087812A1 (en) * 2004-03-05 2005-09-22 Ludwig Institute For Cancer Research Multivalent antibody materials and methods for vegf/pdgf family of growth factors
US7088913B1 (en) * 2004-06-28 2006-08-08 Jcs/Thg, Llc Baseboard/upright heater assembly
CN2835669Y (en) * 2005-09-16 2006-11-08 霍树添 Air blowing mechanism of post type electric fan

Also Published As

Publication number Publication date
JP4532733B2 (en) 2010-08-25
US6455283B1 (en) 2002-09-24
US20080095773A1 (en) 2008-04-24
CY1113126T1 (en) 2016-04-13
US20100331251A1 (en) 2010-12-30
EP1064382A2 (en) 2001-01-03
AU3075099A (en) 1999-10-11
US20090264370A9 (en) 2009-10-22
ES2389387T3 (en) 2012-10-25
US20040235740A1 (en) 2004-11-25
JP2004515201A (en) 2004-05-27
US20080299119A1 (en) 2008-12-04
US6620784B1 (en) 2003-09-16
IL189572A0 (en) 2009-02-11
WO1999047677A2 (en) 1999-09-23
EP1064382B1 (en) 2008-08-20
US20030113870A1 (en) 2003-06-19
JP2010001292A (en) 2010-01-07
JP2013224300A (en) 2013-10-31
CA2322792C (en) 2010-09-14
IL138488A0 (en) 2001-10-31
US20090012003A1 (en) 2009-01-08
US20070031929A1 (en) 2007-02-08
DK2016951T3 (en) 2012-09-24
JP5473441B2 (en) 2014-04-16
EP2016951B1 (en) 2012-06-27
IL189573A0 (en) 2009-02-11
DE69939374D1 (en) 2008-10-02
ATE405651T1 (en) 2008-09-15
CY1108500T1 (en) 2014-04-09
US7494977B2 (en) 2009-02-24
WO1999047677A3 (en) 1999-11-11
AU758353B2 (en) 2003-03-20
IL138488A (en) 2008-06-05
US7371377B2 (en) 2008-05-13
US7575879B2 (en) 2009-08-18
ES2313778T3 (en) 2009-03-01
US20040219640A1 (en) 2004-11-04
DK1064382T3 (en) 2008-12-08
HK1125853A1 (en) 2009-08-21
IL189572A (en) 2013-01-31
JP5931801B2 (en) 2016-06-08
US20110319327A1 (en) 2011-12-29
AU758353C (en) 1999-10-11
IL189571A0 (en) 2009-02-11
PT2016951E (en) 2012-09-27
EP2016951A1 (en) 2009-01-21

Similar Documents

Publication Publication Date Title
CA2322792A1 (en) Polypeptides homologous to vegf and bmp1
Nabi et al. Identification of B16-F1 melanoma autocrine motility-like factor receptor
Aota et al. Characterization of regions of fibronectin besides the arginine-glycine-aspartic acid sequence required for adhesive function of the cell-binding domain using site-directed mutagenesis
US7097986B2 (en) Antibodies to truncated VEGF-D and uses thereof
CA2479476A1 (en) Compositions and methods for the treatment of tumor
CA2225189A1 (en) Canine factor viii gene, protein and methods of use
CA2222279A1 (en) Hypoxia inducible factor-1 and method of use
US7163795B2 (en) Methods and compositions for pearl oyster cultivation
CA2302808A1 (en) 50 human secreted proteins
CA2323776A1 (en) Cytokine receptor common gamma chain like
EP0514481B1 (en) Merosin, nucleic acids encoding, fragments and uses thereof
US5872231A (en) Nucleic acids encoding merosin
WO1995008628A9 (en) Nucleic acids encoding merosin, merosin fragments and uses thereof
AU2002361467A1 (en) Methods and compositions for pearl oyster cultivation
US6974688B2 (en) Human smooth muscle myosin heavy chain
US5591831A (en) Solubilization and purification of the active gastrin releasing peptide receptor
US5624905A (en) Merosin fragments and uses thereof
CA2386141A1 (en) A novel polypeptide and gene encoding the same
CA2323572A1 (en) Vertebrate patched-2 protein
CA2240607A1 (en) Novel vascular smooth muscle cell growth factor
JP2002526075A5 (en)
CA2421339A1 (en) Novel polypeptides and nucleic acids encoding the same
WO2000012551A1 (en) HUMAN LATENT TRANSFORMING GROWTH FACTOR-β BINDING PROTEIN 3
JPH1149701A (en) Anticancer agent
JP2002537812A5 (en)

Legal Events

Date Code Title Description
EEER Examination request
MKEX Expiry

Effective date: 20190311