WO2002072605A2 - Expression technology for proteins containing a hybrid isotype antibody moiety - Google Patents
Expression technology for proteins containing a hybrid isotype antibody moiety Download PDFInfo
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- WO2002072605A2 WO2002072605A2 PCT/US2002/007011 US0207011W WO02072605A2 WO 2002072605 A2 WO2002072605 A2 WO 2002072605A2 US 0207011 W US0207011 W US 0207011W WO 02072605 A2 WO02072605 A2 WO 02072605A2
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- fusion protein
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/53—Hinge
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cell Biology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
Claims
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
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ES02717581T ES2393733T3 (en) | 2001-03-07 | 2002-03-07 | Expression technology for proteins that contain a hybrid isotype antibody fraction |
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BR0207854-6A BR0207854A (en) | 2001-03-07 | 2002-03-07 | Expression technology for proteins containing a hybrid isotype antibody moiety |
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US7790415B2 (en) | 2000-02-11 | 2010-09-07 | Merck Patent Gmbh | Enhancing the circulating half-life of antibody-based fusion proteins |
US7820155B2 (en) | 2005-12-30 | 2010-10-26 | Merck Patent Gmbh | Methods of treating cancer comprising administering an interleukin-6 antibody variable region |
US7829084B2 (en) | 2001-01-17 | 2010-11-09 | Trubion Pharmaceuticals, Inc. | Binding constructs and methods for use thereof |
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US7955590B2 (en) | 1999-07-21 | 2011-06-07 | Merck Patent Gmbh | Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
WO2011064758A3 (en) * | 2009-11-30 | 2011-08-04 | Pfizer Limited | Fusion proteins of immunoglobulin fc and interferon- alpha |
EP2409991A1 (en) * | 2009-03-19 | 2012-01-25 | Chugai Seiyaku Kabushiki Kaisha | Antibody constant region variant |
US8106161B2 (en) | 2001-01-17 | 2012-01-31 | Emergent Product Development Seattle, Llc | Binding domain-immunoglobulin fusion proteins |
US8222016B2 (en) | 2007-06-29 | 2012-07-17 | Daiichi Sankyo Company, Limited | Recombinant C-terminal α-amidating enzyme derivative |
US8333966B2 (en) | 2008-04-11 | 2012-12-18 | Emergent Product Development Seattle, Llc | CD37 immunotherapeutics and uses thereof |
US8409577B2 (en) | 2006-06-12 | 2013-04-02 | Emergent Product Development Seattle, Llc | Single chain multivalent binding proteins with effector function |
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Families Citing this family (90)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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US8518403B2 (en) * | 2004-07-16 | 2013-08-27 | Amgen Research (Munich) Gmbh | Expression-enhanced polypeptides |
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WO2007024743A2 (en) * | 2005-08-19 | 2007-03-01 | Centocor, Inc. | Proteolysis resistant antibody preparations |
US20070104689A1 (en) * | 2005-09-27 | 2007-05-10 | Merck Patent Gmbh | Compositions and methods for treating tumors presenting survivin antigens |
WO2007067828A2 (en) * | 2005-10-24 | 2007-06-14 | Centocor, Inc. | Glp-2 mimetibodies, polypeptides, compositions, methods and uses |
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PT1966238E (en) | 2005-12-30 | 2012-07-31 | Merck Patent Gmbh | Interleukin-12p40 variants with improved stability |
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KR100949982B1 (en) * | 2006-03-30 | 2010-03-29 | 엘지전자 주식회사 | A method and apparatus for decoding/encoding a video signal |
JP2009542592A (en) * | 2006-07-06 | 2009-12-03 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | Compositions and methods for enhancing the effectiveness of an IL-2-mediated immune response |
NZ581395A (en) * | 2007-05-14 | 2012-08-31 | Biogen Idec Inc | Single-chain fc (scfc) regions, binding polypeptides comprising same, and methods related thereto |
JP5168538B2 (en) * | 2007-05-24 | 2013-03-21 | アボットジャパン株式会社 | Antibody-antibody conjugates and application to diagnostic antibodies |
CN101990439A (en) * | 2007-07-06 | 2011-03-23 | 特鲁比昂药品公司 | Binding peptides having a c-terminally disposed specific binding domain |
BRPI0821110B8 (en) | 2007-12-05 | 2021-05-25 | Chugai Pharmaceutical Co Ltd | anti-nr10/il31ra neutralizing antibody, pharmaceutical composition comprising said antibody and use thereof |
US8557243B2 (en) * | 2008-01-03 | 2013-10-15 | The Scripps Research Institute | EFGR antibodies comprising modular recognition domains |
AU2008346734A1 (en) * | 2008-01-03 | 2009-07-16 | The Scripps Research Institute | Antibody targeting through a modular recognition domain |
US8454960B2 (en) * | 2008-01-03 | 2013-06-04 | The Scripps Research Institute | Multispecific antibody targeting and multivalency through modular recognition domains |
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US8557242B2 (en) * | 2008-01-03 | 2013-10-15 | The Scripps Research Institute | ERBB2 antibodies comprising modular recognition domains |
CA2759333A1 (en) | 2009-04-22 | 2010-10-28 | Merck Patent Gmbh | Antibody fusion proteins with modified fcrn binding sites |
BR112012010252A2 (en) * | 2009-10-29 | 2016-12-06 | Janssen Biotech Inc | antibody glycosylation variants |
CN101870735B (en) * | 2010-06-02 | 2013-06-12 | 北京精益泰翔技术发展有限公司 | High-glycosylation erythropoietin immune fusion protein |
WO2012009705A1 (en) | 2010-07-15 | 2012-01-19 | Zyngenia, Inc. | Ang-2 binding complexes and uses thereof |
US8883134B2 (en) | 2010-10-20 | 2014-11-11 | Handok Pharmaceuticals, Inc. | Human interleukin-1 receptor antagonist—hybrid Fc fusion protein |
EP3626739A1 (en) | 2011-06-24 | 2020-03-25 | Stephen D. Gillies | Light chain immunoglobulin fusion proteins and methods of use thereof |
CN103857700A (en) * | 2011-08-26 | 2014-06-11 | 梅里麦克制药股份有限公司 | Tandem FC bispecific antibodies |
WO2013049254A1 (en) * | 2011-09-26 | 2013-04-04 | Jn Biosciences Llc | Hybrid constant regions |
US9382319B2 (en) | 2011-09-26 | 2016-07-05 | Jn Biosciences Llc | Hybrid constant regions |
US9809641B2 (en) | 2012-04-23 | 2017-11-07 | Nrl Pharma, Inc. | Lactoferrin fusion protein and method for preparation thereof |
EP2708556B1 (en) | 2012-09-12 | 2018-11-07 | Samsung Electronics Co., Ltd | Pharmaceutical composition for the use in a combination therapy for prevention or treatment of c-met or angiogenesis factor induced diseases |
US20160009824A1 (en) | 2013-03-15 | 2016-01-14 | Merck Patent Gmbh | Tetravalent bispecific antibodies |
EA201890895A1 (en) | 2013-03-15 | 2019-02-28 | Зинджения, Инк. | MULTIVALENT AND MONOVALENT MULTIS-SPECIFIC COMPLEXES AND THEIR APPLICATION |
US20150038682A1 (en) * | 2013-08-02 | 2015-02-05 | Jn Biosciences Llc | Antibodies or fusion proteins multimerized via homomultimerizing peptide |
JP6623353B2 (en) | 2013-09-13 | 2019-12-25 | ベイジーン スウィッツァーランド ゲーエムベーハー | Anti-PD-1 antibodies and their use for therapy and diagnosis |
US9717715B2 (en) | 2013-11-15 | 2017-08-01 | Samsung Electronics Co., Ltd. | Method of combination therapy using an anti-C-Met antibody |
DK3105246T3 (en) | 2014-02-10 | 2021-06-14 | Merck Patent Gmbh | Targeted TGF-beta inhibition |
JP6851200B2 (en) | 2014-03-05 | 2021-03-31 | ユーシービー バイオファルマ エスアールエル | Multimeric Fc protein |
SG11201608194VA (en) * | 2014-04-03 | 2016-10-28 | Igm Biosciences Inc | Modified j-chain |
JP6526189B2 (en) | 2014-07-03 | 2019-06-05 | ベイジーン リミテッド | Anti-PD-L1 antibodies and their use for therapy and diagnosis |
BR112017001385B1 (en) | 2014-07-22 | 2023-12-05 | Cb Therapeutics, Inc. | ISOLATED ANTIBODY OR FRAGMENT THEREOF THAT BINDS PD-1, USE OF IT, COMPOSITION, ISOLATED POLYNUCLEOTIDE AND EXPRESSION VECTOR |
KR102476226B1 (en) | 2014-08-05 | 2022-12-12 | 아폴로믹스 인코포레이티드 | Anti-pd-l1 antibodies |
HUE043038T2 (en) | 2014-08-11 | 2019-07-29 | Delinia Inc | Modified il-2 variants that selectively activate regulatory t cells for the treatment of autoimmune diseases |
CN107810202A (en) | 2015-02-17 | 2018-03-16 | 韩美药品株式会社 | Protamine zine insulin or insulin analog compound |
EP3878857A1 (en) * | 2015-04-22 | 2021-09-15 | Biogen MA Inc. | Novel hybrid actriib ligand trap proteins for treating muscle wasting diseases |
WO2017004083A1 (en) * | 2015-06-29 | 2017-01-05 | The Regents Of The University Of California | Methods of producing nucleic acid libraries and compositions and kits for practicing same |
US10618978B2 (en) | 2015-09-30 | 2020-04-14 | Igm Biosciences, Inc. | Binding molecules with modified J-chain |
ES2819870T3 (en) | 2015-09-30 | 2021-04-19 | Igm Biosciences Inc | Modified J-chain binding molecules |
US20180271998A1 (en) | 2015-12-04 | 2018-09-27 | Merrimack Pharmaceuticals, Inc. | Disulfide-stabilized fabs |
US20170204154A1 (en) | 2016-01-20 | 2017-07-20 | Delinia, Inc. | Molecules that selectively activate regulatory t cells for the treatment of autoimmune diseases |
CN109475536B (en) | 2016-07-05 | 2022-05-27 | 百济神州有限公司 | Combination of a PD-l antagonist and a RAF inhibitor for the treatment of cancer |
KR20230125859A (en) | 2016-08-12 | 2023-08-29 | 메르크 파텐트 게엠베하 | Combination therapy for cancer |
AU2017313085A1 (en) | 2016-08-19 | 2019-03-14 | Beigene Switzerland Gmbh | Use of a combination comprising a Btk inhibitor for treating cancers |
JP7142915B2 (en) | 2016-10-28 | 2022-09-28 | 株式会社S&Kバイオファーマ | Lactoferrin/albumin fusion protein and method for producing same |
EA201991142A1 (en) | 2016-11-08 | 2019-10-31 | OPTIONS IL-2 FOR TREATMENT OF AUTOIMMUNE DISEASES | |
US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
CN110461847B (en) | 2017-01-25 | 2022-06-07 | 百济神州有限公司 | Crystalline forms of (S) -7- (1- (but-2-alkynoyl) piperidin-4-yl) -2- (4-phenoxyphenyl) -4,5,6, 7-tetrahydropyrazolo [1,5-a ] pyrimidine-3-carboxamide, preparation and use thereof |
CA3066518A1 (en) | 2017-06-26 | 2019-01-03 | Beigene, Ltd. | Immunotherapy for hepatocellular carcinoma |
EP3650539A4 (en) * | 2017-07-07 | 2021-08-18 | Hanmi Pharm. Co., Ltd. | Novel therapeutic enzyme fusion protein and use thereof |
WO2019108795A1 (en) | 2017-11-29 | 2019-06-06 | Beigene Switzerland Gmbh | Treatment of indolent or aggressive b-cell lymphomas using a combination comprising btk inhibitors |
CR20200392A (en) | 2018-03-09 | 2020-11-17 | Agenus Inc | Anti-cd73 antibodies and methods of use thereof |
EP3873612A2 (en) | 2018-11-01 | 2021-09-08 | Merck Patent GmbH | Methods of administering anti-tim-3 antibodies |
CA3117429A1 (en) | 2018-11-01 | 2020-05-07 | Merck Patent Gmbh | Anti-tim-3 antibodies |
US20220056135A1 (en) | 2018-12-21 | 2022-02-24 | Ose Immunotherapeutics | Bifunctional anti-pd-1/sirpa molecule |
US20220025050A1 (en) | 2018-12-21 | 2022-01-27 | Ose Immunotherapeutics | Bifunctional molecule directed against human pd-1 |
CN113614109A (en) | 2018-12-21 | 2021-11-05 | Ose免疫疗法公司 | Bifunctional anti-PD-1/IL-7 molecules |
DK3883966T3 (en) | 2018-12-21 | 2023-10-16 | Ose Immunotherapeutics | HUMANIZED ANTI-HUMAN PD-1 ANTIBODY |
WO2020165374A1 (en) | 2019-02-14 | 2020-08-20 | Ose Immunotherapeutics | Bifunctional molecule comprising il-15ra |
CA3224182A1 (en) * | 2021-06-17 | 2022-12-22 | Fapon Biotech Inc. | Chimeric immunoglobulin |
US20230190799A1 (en) * | 2021-07-21 | 2023-06-22 | City Of Hope | Chimeric antigen receptor t cells targeting cea and anti-cea-il2 immunocytokines for cancer therapy |
WO2023076927A1 (en) * | 2021-10-27 | 2023-05-04 | Anwita Biosciences, Inc. | Il-2 fusion proteins, pharmaceutical compositions, and therapeutic applications |
CN114835810B (en) * | 2022-03-31 | 2024-01-05 | 浙江特瑞思药业股份有限公司 | anti-PD-1 nano antibody and application thereof |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1991004329A1 (en) * | 1989-09-20 | 1991-04-04 | Abbott Laboratories | Method of producing fusion proteins |
WO1991013166A1 (en) * | 1990-03-02 | 1991-09-05 | Abbott Biotech, Inc. | Antibody constructs with enhanced binding affinity |
WO1999043713A1 (en) * | 1998-02-25 | 1999-09-02 | Lexigen Pharmaceuticals Corporation | Enhancing the circulating half-life of antibody-based fusion proteins |
WO2000069913A1 (en) * | 1999-05-19 | 2000-11-23 | Lexigen Pharmaceuticals Corp. | EXPRESSION AND EXPORT OF INTERFERON-ALPHA PROTEINS AS Fc FUSION PROTEINS |
Family Cites Families (186)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US81664A (en) * | 1868-09-01 | Island | ||
US193570A (en) * | 1877-07-24 | Improvement in washing-boards | ||
US3529A (en) * | 1844-04-10 | yvolfe | ||
US105294A (en) * | 1870-07-12 | Erasmus w | ||
US147311A (en) * | 1874-02-10 | Improvement in electric telegraphs | ||
US192222A (en) * | 1877-06-19 | Improvement in watches | ||
US166877A (en) * | 1875-08-17 | Improvement in electric lights | ||
US44423A (en) * | 1864-09-27 | Improved screw for music-stools | ||
US12789A (en) * | 1855-05-01 | Office | ||
US49227A (en) * | 1865-08-08 | Improvement in construction of railway trains and cars | ||
US53539A (en) * | 1866-03-27 | Improvement in revolving fire-arms | ||
US4196265A (en) | 1977-06-15 | 1980-04-01 | The Wistar Institute | Method of producing antibodies |
US4522811A (en) * | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
US4469797A (en) | 1982-09-23 | 1984-09-04 | Miles Laboratories, Inc. | Digoxigenin immunogens, antibodies, labeled conjugates, and related derivatives |
US4737462A (en) * | 1982-10-19 | 1988-04-12 | Cetus Corporation | Structural genes, plasmids and transformed cells for producing cysteine depleted muteins of interferon-β |
US4966843A (en) * | 1982-11-01 | 1990-10-30 | Cetus Corporation | Expression of interferon genes in Chinese hamster ovary cells |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4703008A (en) | 1983-12-13 | 1987-10-27 | Kiren-Amgen, Inc. | DNA sequences encoding erythropoietin |
NZ210501A (en) | 1983-12-13 | 1991-08-27 | Kirin Amgen Inc | Erythropoietin produced by procaryotic or eucaryotic expression of an exogenous dna sequence |
KR850004274A (en) | 1983-12-13 | 1985-07-11 | 원본미기재 | Method for preparing erythropoietin |
US5082658A (en) * | 1984-01-16 | 1992-01-21 | Genentech, Inc. | Gamma interferon-interleukin-2 synergism |
EP0158198A1 (en) | 1984-03-29 | 1985-10-16 | Takeda Chemical Industries, Ltd. | DNA and use thereof |
US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
US4667016A (en) * | 1985-06-20 | 1987-05-19 | Kirin-Amgen, Inc. | Erythropoietin purification |
US4690915A (en) | 1985-08-08 | 1987-09-01 | The United States Of America As Represented By The Department Of Health And Human Services | Adoptive immunotherapy as a treatment modality in humans |
US5679543A (en) | 1985-08-29 | 1997-10-21 | Genencor International, Inc. | DNA sequences, vectors and fusion polypeptides to increase secretion of desired polypeptides from filamentous fungi |
US5643565A (en) | 1985-09-20 | 1997-07-01 | Chiron Corporation | Human IL-2 as a vaccine adjuvant |
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 |
US4935233A (en) | 1985-12-02 | 1990-06-19 | G. D. Searle And Company | Covalently linked polypeptide cell modulators |
DE3712985A1 (en) | 1987-04-16 | 1988-11-03 | Hoechst Ag | BIFUNCTIONAL PROTEINS |
US5359035A (en) | 1985-12-21 | 1994-10-25 | Hoechst Aktiengesellschaft | Bifunctional proteins including interleukin-2 (IL-2) and granuloctyte macrophage colony stimulating factor (GM-CSF) |
EP0237019A3 (en) | 1986-03-14 | 1988-03-09 | Toray Industries, Inc. | Interferon conjugate and production thereof using recombinant gene |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
DK173067B1 (en) | 1986-06-27 | 1999-12-13 | Univ Washington | Human erythropoietin gene, method of expression thereof in transfected cell lines, the transfected cell lines |
US4894227A (en) | 1986-08-01 | 1990-01-16 | Cetus Corporation | Composition of immunotoxins with interleukin-2 |
US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
US5508031A (en) | 1986-11-21 | 1996-04-16 | Cetus Oncology Corporation | Method for treating biological damage using a free-radial scavenger and interleukin-2 |
US4732683A (en) * | 1986-12-02 | 1988-03-22 | Biospectrum, Inc. | Purification method for alpha interferon |
US5019368A (en) | 1989-02-23 | 1991-05-28 | Cancer Biologics, Inc. | Detection of necrotic malignant tissue and associated therapy |
EP0307434B2 (en) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
ATE120761T1 (en) | 1987-05-21 | 1995-04-15 | Creative Biomolecules Inc | MULTIFUNCTIONAL PROTEINS WITH PREDEFINED TARGET. |
US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
US5091513A (en) * | 1987-05-21 | 1992-02-25 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
EP0294703B1 (en) | 1987-06-10 | 1995-05-10 | Dana-Farber Cancer Institute, Inc. | Bifunctional antibody constructs and method for selectively destroying cell populations |
US5064646A (en) | 1988-08-02 | 1991-11-12 | The University Of Maryland | Novel infectious bursal disease virus |
PH26813A (en) | 1987-09-02 | 1992-11-05 | Ciba Geigy Ag | Conjugates of cytokines with immunoglobulins |
GB8720833D0 (en) * | 1987-09-04 | 1987-10-14 | Celltech Ltd | Recombinant dna product |
US5677425A (en) * | 1987-09-04 | 1997-10-14 | Celltech Therapeutics Limited | Recombinant antibody |
CA1338518C (en) | 1987-09-23 | 1996-08-13 | Joyce M. Zarling | Antibody heteroconjugates for the killing of hiv-infected cells |
NZ226414A (en) | 1987-10-02 | 1992-07-28 | Genentech Inc | Cd4 peptide adhesion variants and their preparation and use |
ZA888978B (en) | 1987-12-04 | 1990-07-25 | Du Pont | Immobilized interleukin 2 and interleukin 2 containing a carboxylterminal extension |
WO1989006692A1 (en) | 1988-01-12 | 1989-07-27 | Genentech, Inc. | Method of treating tumor cells by inhibiting growth factor receptor function |
CA1341588C (en) | 1988-01-26 | 2009-01-06 | Michel Revel | Human ifn-beta2/i1-6, its purification and use |
US5120525A (en) | 1988-03-29 | 1992-06-09 | Immunomedics, Inc. | Radiolabeled antibody cytotoxic therapy of cancer |
US4975369A (en) | 1988-04-21 | 1990-12-04 | Eli Lilly And Company | Recombinant and chimeric KS1/4 antibodies directed against a human adenocarcinoma antigen |
IT1217724B (en) | 1988-05-26 | 1990-03-30 | Ist Naz Ric Sul Cancro | SPECIFIC MONOCLONAL ANTIBODY FOR A SEQUENCE OF FIBRONETIN EXPRESSED IN TRANSFORMED HYBRID CELLS ACCORDING TO SUCH ANTIBODY AND USE OF THE MONOCLONAL ANTIBODY FOR THE DIAGNOSIS OF TUMORS |
IE62463B1 (en) | 1988-07-07 | 1995-02-08 | Res Dev Foundation | Immunoconjugates for cancer diagnosis and therapy |
US5601819A (en) * | 1988-08-11 | 1997-02-11 | The General Hospital Corporation | Bispecific antibodies for selective immune regulation and for selective immune cell binding |
US5457038A (en) | 1988-11-10 | 1995-10-10 | Genetics Institute, Inc. | Natural killer stimulatory factor |
US5242824A (en) | 1988-12-22 | 1993-09-07 | Oncogen | Monoclonal antibody to human carcinomas |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5116964A (en) | 1989-02-23 | 1992-05-26 | Genentech, Inc. | Hybrid immunoglobulins |
US5225538A (en) | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
US5166322A (en) | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
IE63847B1 (en) | 1989-05-05 | 1995-06-14 | Res Dev Foundation | A novel antibody delivery system for biological response modifiers |
US6291158B1 (en) | 1989-05-16 | 2001-09-18 | Scripps Research Institute | Method for tapping the immunological repertoire |
US5399346A (en) * | 1989-06-14 | 1995-03-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gene therapy |
EP0406857B1 (en) | 1989-07-07 | 1995-05-24 | Takeda Chemical Industries, Ltd. | Proteins and production thereof |
US5073627A (en) | 1989-08-22 | 1991-12-17 | Immunex Corporation | Fusion proteins comprising GM-CSF and IL-3 |
JP2983629B2 (en) | 1989-10-13 | 1999-11-29 | キリン―アムジエン・インコーポレイテツド | Erythropoietin isoform |
US5856298A (en) | 1989-10-13 | 1999-01-05 | Amgen Inc. | Erythropoietin isoforms |
ATE369383T1 (en) | 1989-12-22 | 2007-08-15 | Hoffmann La Roche | MONOCLONAL ANTIBODIES SPECIFIC TO THE CYTOTOXIC LYMPHOCYTE MATURATION FACTOR |
US5314995A (en) | 1990-01-22 | 1994-05-24 | Oncogen | Therapeutic interleukin-2-antibody based fusion proteins |
US5349053A (en) | 1990-06-01 | 1994-09-20 | Protein Design Labs, Inc. | Chimeric ligand/immunoglobulin molecules and their uses |
US7253264B1 (en) | 1990-06-28 | 2007-08-07 | Sanofi-Arentideutschland GmbH | Immunoglobulin fusion proteins, their production and use |
US5770429A (en) * | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5650150A (en) | 1990-11-09 | 1997-07-22 | Gillies; Stephen D. | Recombinant antibody cytokine fusion proteins |
US5709859A (en) | 1991-01-24 | 1998-01-20 | Bristol-Myers Squibb Company | Mixed specificity fusion proteins |
US6072039A (en) | 1991-04-19 | 2000-06-06 | Rohm And Haas Company | Hybrid polypeptide comparing a biotinylated avidin binding polypeptide fused to a polypeptide of interest |
EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
US5199942A (en) | 1991-06-07 | 1993-04-06 | Immunex Corporation | Method for improving autologous transplantation |
DE69227693T2 (en) | 1991-08-30 | 1999-07-22 | Hutchinson Fred Cancer Res | HYBRID CYTOKINE |
US20020037558A1 (en) | 1991-10-23 | 2002-03-28 | Kin-Ming Lo | E.coli produced immunoglobulin constructs |
US5277375A (en) * | 1991-12-04 | 1994-01-11 | The Procter & Gamble Company | Spindle for use with compressed core wound paper products |
US6627615B1 (en) | 1991-12-17 | 2003-09-30 | The Regents Of The University Of California | Methods and compositions for in vivo gene therapy |
EP0633929B1 (en) | 1992-04-01 | 2004-03-03 | The Rockefeller University | METHOD FOR $i(IN VITRO) PROLIFERATION OF DENDRITIC CELL PRECURSORS AND THEIR USE TO PRODUCE IMMUNOGENS |
WO1993024135A1 (en) * | 1992-05-26 | 1993-12-09 | Immunex Corporation | Novel cytokine that binds cd30 |
IL105914A0 (en) | 1992-06-04 | 1993-10-20 | Univ California | Methods and compositions for in vivo gene therapy |
US5614184A (en) * | 1992-07-28 | 1997-03-25 | New England Deaconess Hospital | Recombinant human erythropoietin mutants and therapeutic methods employing them |
CA2142007C (en) | 1992-08-11 | 2007-10-30 | Robert Glen Urban | Immunomodulatory peptides |
DE4228839A1 (en) | 1992-08-29 | 1994-03-03 | Behringwerke Ag | Methods for the detection and determination of mediators |
US5837821A (en) | 1992-11-04 | 1998-11-17 | City Of Hope | Antibody construct |
EP1757694A3 (en) | 1992-11-05 | 2008-02-27 | Sloan Kettering Institute For Cancer Research | Prostate-specific membrane antigen |
US5738849A (en) | 1992-11-24 | 1998-04-14 | G. D. Searle & Co. | Interleukin-3 (IL-3) variant fusion proteins, their recombinant production, and therapeutic compositions comprising them |
US5543297A (en) | 1992-12-22 | 1996-08-06 | Merck Frosst Canada, Inc. | Human cyclooxygenase-2 cDNA and assays for evaluating cyclooxygenase-2 activity |
US6096331A (en) | 1993-02-22 | 2000-08-01 | Vivorx Pharmaceuticals, Inc. | Methods and compositions useful for administration of chemotherapeutic agents |
KR960701988A (en) * | 1993-04-20 | 1996-03-28 | 윌리엄 에스. 로빈슨 | METHODS AND MATERIALS FOR TREATMENT OF INDIVIDUALS INFECTED WITH INTRACELLULAR IN-FECTIOUS AGENTS |
US5759551A (en) | 1993-04-27 | 1998-06-02 | United Biomedical, Inc. | Immunogenic LHRH peptide constructs and synthetic universal immune stimulators for vaccines |
JPH08509614A (en) | 1993-04-29 | 1996-10-15 | アボツト・ラボラトリーズ | Erythropoietin analog compositions and methods |
US5554512A (en) | 1993-05-24 | 1996-09-10 | Immunex Corporation | Ligands for flt3 receptors |
CA2125763C (en) | 1993-07-02 | 2007-08-28 | Maurice Kent Gately | P40 homodimer of interleukin-12 |
US5609876A (en) * | 1993-08-09 | 1997-03-11 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Peptide vaccines and associated methods for protection against feline leukemia virus |
IL192290A0 (en) | 1993-08-17 | 2008-12-29 | Kirin Amgen Inc | Erythropoietin analogs |
EP0758390B1 (en) | 1994-04-26 | 2007-02-28 | The Children's Medical Center Corporation | Angiostatin and method of use for inhibition of angiogenesis |
US5837682A (en) | 1996-03-08 | 1998-11-17 | The Children's Medical Center Corporation | Angiostatin fragments and method of use |
US5639725A (en) | 1994-04-26 | 1997-06-17 | Children's Hospital Medical Center Corp. | Angiostatin protein |
CU22615A1 (en) | 1994-06-30 | 2000-02-10 | Centro Inmunologia Molecular | PROCEDURE FOR OBTAINING LESS IMMUNOGENIC MONOCLONAL ANTIBODIES. MONOCLONAL ANTIBODIES OBTAINED |
US6429199B1 (en) | 1994-07-15 | 2002-08-06 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules for activating dendritic cells |
US6309853B1 (en) | 1994-08-17 | 2001-10-30 | The Rockfeller University | Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof |
US5888773A (en) * | 1994-08-17 | 1999-03-30 | The United States Of America As Represented By The Department Of Health And Human Services | Method of producing single-chain Fv molecules |
US5541087A (en) | 1994-09-14 | 1996-07-30 | Fuji Immunopharmaceuticals Corporation | Expression and export technology of proteins as immunofusins |
ES2167391T3 (en) | 1994-09-16 | 2002-05-16 | Merck Patent Gmbh | IMMUNOCONJUGADOS II. |
JP3429578B2 (en) * | 1994-10-31 | 2003-07-22 | オリンパス光学工業株式会社 | Small rear focus zoom lens |
US6485726B1 (en) | 1995-01-17 | 2002-11-26 | The Brigham And Women's Hospital, Inc. | Receptor specific transepithelial transport of therapeutics |
US6086875A (en) | 1995-01-17 | 2000-07-11 | The Brigham And Women's Hospital, Inc. | Receptor specific transepithelial transport of immunogens |
US5691309A (en) | 1995-01-31 | 1997-11-25 | Eli Lilly And Company | Anti-obesity proteins |
US5552524A (en) | 1995-01-31 | 1996-09-03 | Eli Lilly And Company | Anti-obesity proteins |
US5891680A (en) | 1995-02-08 | 1999-04-06 | Whitehead Institute For Biomedical Research | Bioactive fusion proteins comprising the p35 and p40 subunits of IL-12 |
JP3342873B2 (en) | 1995-03-10 | 2002-11-11 | ジェネンテク・インコーポレイテッド | Receptor activation by gas6 |
US5719266A (en) | 1995-03-17 | 1998-02-17 | Eli Lilly And Company | Anti-obesity proteins |
US6281010B1 (en) * | 1995-06-05 | 2001-08-28 | The Trustees Of The University Of Pennsylvania | Adenovirus gene therapy vehicle and cell line |
JPH11508895A (en) | 1995-06-30 | 1999-08-03 | イーライ・リリー・アンド・カンパニー | How to treat diabetes |
US6406689B1 (en) | 1995-10-03 | 2002-06-18 | Frank W. Falkenberg | Compositions and methods for treatment of tumors and metastatic diseases |
US5854205A (en) | 1995-10-23 | 1998-12-29 | The Children's Medical Center Corporation | Therapeutic antiangiogenic compositions and methods |
US6620413B1 (en) * | 1995-12-27 | 2003-09-16 | Genentech, Inc. | OB protein-polymer chimeras |
US6080409A (en) | 1995-12-28 | 2000-06-27 | Dendreon Corporation | Immunostimulatory method |
US5723125A (en) | 1995-12-28 | 1998-03-03 | Tanox Biosystems, Inc. | Hybrid with interferon-alpha and an immunoglobulin Fc linked through a non-immunogenic peptide |
US6750334B1 (en) * | 1996-02-02 | 2004-06-15 | Repligen Corporation | CTLA4-immunoglobulin fusion proteins having modified effector functions and uses therefor |
CA2205757C (en) | 1996-05-30 | 2006-01-24 | F. Hoffmann-La Roche Ag | Pyridazinone derivatives and their use as inhibitors of prostaglandin g/h synthase i and ii(cox i and ii) |
US5922685A (en) | 1996-06-05 | 1999-07-13 | Powderject Vaccines, Inc. | IL-12 gene therapy of tumors |
ES2176574T3 (en) * | 1996-09-03 | 2002-12-01 | Gsf Forschungszentrum Umwelt | USE OF BI AND TRIESPECIFIC ANTIBODIES FOR INDUCTION OF TUMOR IMMUNITY. |
US5994104A (en) | 1996-11-08 | 1999-11-30 | Royal Free Hospital School Of Medicine | Interleukin-12 fusion protein |
US6100387A (en) | 1997-02-28 | 2000-08-08 | Genetics Institute, Inc. | Chimeric polypeptides containing chemokine domains |
US6277375B1 (en) | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
ES2187954T3 (en) | 1997-04-11 | 2003-06-16 | Searle & Co | ANTI-INTEGRINE ANTIBODIES AVB3 ANTAGONISTS. |
AU8182298A (en) * | 1997-07-10 | 1999-02-08 | Beth Israel Deaconess Medical Center | Recombinant erythropoietin / immunoglobulin fusion proteins |
DE69824039T2 (en) | 1997-12-08 | 2005-08-18 | Lexigen Pharmaceuticals Corp., Lexington | HETERODIMARY FUSION PROTEINS FOR THE USE OF TARGETED IMMUNOTHERAPY AND GENERAL IMMUNE REGION |
US20030105294A1 (en) | 1998-02-25 | 2003-06-05 | Stephen Gillies | Enhancing the circulating half life of antibody-based fusion proteins |
PL343462A1 (en) | 1998-04-15 | 2001-08-13 | Lexigen Pharm Corp | Enhancement of antibody-cytokine fusion protein mediated immune responses by co-administration with angiogenesis inhibitor |
RU2217168C2 (en) * | 1998-04-17 | 2003-11-27 | Лексиген Фармасьютикэлс Корпорейшн | Enhancement of immune response mediated by proteins fused of antibody and cytokine by means of combined administration of prostaglandin inhibitor |
AU3655899A (en) * | 1998-04-20 | 1999-11-08 | Regents Of The University Of California, The | Modified immunoglobulin molecules and methods for use thereof |
AU751823B2 (en) | 1998-05-14 | 2002-08-29 | Merck Patent Gmbh | Fused protein |
US6620382B1 (en) | 1998-05-22 | 2003-09-16 | Biopheresis Technologies, Llc. | Method and compositions for treatment of cancers |
EP1105427A2 (en) * | 1998-08-17 | 2001-06-13 | Abgenix, Inc. | Generation of modified molecules with increased serum half-lives |
BR9913331A (en) | 1998-08-25 | 2001-05-15 | Lexigen Pharm Corp | Expression and export of angiogenesis inhibitors as immunofusins |
US6646113B1 (en) | 1998-09-17 | 2003-11-11 | The Trustees Of The University Of Pennsylvania | Nucleic acid molecule encoding human survival of motor neuron-interacting protein 1 (SIP1) deletion mutants |
US6335176B1 (en) * | 1998-10-16 | 2002-01-01 | Pharmacopeia, Inc. | Incorporation of phosphorylation sites |
SK9432001A3 (en) * | 1999-01-07 | 2003-02-04 | Lexigen Pharm Corp | Expression and export of anti-obesity proteins as Fc fusion proteins |
KR100773109B1 (en) | 1999-05-06 | 2007-11-02 | 웨이크 포리스트 유니버시티 | Compositions And Methods For Identifying Antigens Which Elicit An Immune Response |
US6348192B1 (en) | 1999-05-11 | 2002-02-19 | Bayer Corporation | Interleukin-2 mutein expressed from mammalian cells |
JO2291B1 (en) | 1999-07-02 | 2005-09-12 | اف . هوفمان لاروش ايه جي | Erythopintin derivatives |
CZ299516B6 (en) | 1999-07-02 | 2008-08-20 | F. Hoffmann-La Roche Ag | Erythropoietin glycoprotein conjugate, process for its preparation and use and pharmaceutical composition containing thereof |
SK782002A3 (en) | 1999-07-21 | 2003-08-05 | Lexigen Pharm Corp | FC fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
US7067110B1 (en) | 1999-07-21 | 2006-06-27 | Emd Lexigen Research Center Corp. | Fc fusion proteins for enhancing the immunogenicity of protein and peptide antigens |
MXPA02000962A (en) * | 1999-07-29 | 2002-07-02 | Medarex Inc | Human monoclonal antibodies to her2 neu. |
BR0013231A (en) * | 1999-08-09 | 2002-07-23 | Lexigen Pharm Corp | Multiple cytokine-antibody complexes |
EP1228214A2 (en) | 1999-11-12 | 2002-08-07 | MERCK PATENT GmbH | Erythropoietin forms with improved properties |
US20050202538A1 (en) | 1999-11-12 | 2005-09-15 | Merck Patent Gmbh | Fc-erythropoietin fusion protein with improved pharmacokinetics |
ES2269366T3 (en) | 2000-02-11 | 2007-04-01 | Merck Patent Gmbh | IMPROVEMENT OF AVERAGE LIFE IN CIRCULATION OF FUSION PROTEINS BASED ON ANTIBODIES. |
DE60121733T2 (en) * | 2000-02-24 | 2007-08-09 | Philogen S.P.A. | Compositions and methods for the treatment of angiogenesis in pathological lesions |
US6586398B1 (en) | 2000-04-07 | 2003-07-01 | Amgen, Inc. | Chemically modified novel erythropoietin stimulating protein compositions and methods |
US20020019342A1 (en) | 2000-05-12 | 2002-02-14 | Robert Bayer | In vitro modification of glycosylation patterns of recombinant glycopeptides |
DE60129695T2 (en) | 2000-06-29 | 2008-06-05 | Merck Patent Gmbh | INCREASING IMMUNE RESPONSES MEDIATED BY ANTIBODY CYTOKIN FUSION PROTEINS BY COMBINED TREATMENT WITH MEDICAMENTS FOR INCREASING IMMUNOCYTIC INJECTION |
US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
JP2004525621A (en) * | 2001-01-18 | 2004-08-26 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | Bifunctional fusion protein having glucocerebrosidase activity |
RU2363707C2 (en) * | 2001-02-19 | 2009-08-10 | Мерк Патент Гмбх | Artificial proteins with lowered adjuvanticity |
EP1998266A3 (en) | 2001-02-19 | 2009-02-11 | Merck Patent GmbH | Method for identification of T-cell epitopes and use for preparing molecules with reduced immunogenicity |
BR0207854A (en) | 2001-03-07 | 2004-08-24 | Merck Patent Gmbh | Expression technology for proteins containing a hybrid isotype antibody moiety |
US6992174B2 (en) | 2001-03-30 | 2006-01-31 | Emd Lexigen Research Center Corp. | Reducing the immunogenicity of fusion proteins |
DE60239454D1 (en) | 2001-05-03 | 2011-04-28 | Merck Patent Gmbh | RECOMBINANT, TUMOR-SPECIFIC ANTIBODY AND ITS USE |
ES2381025T3 (en) | 2001-12-04 | 2012-05-22 | Merck Patent Gmbh | Immunocytokines with modulated selectivity |
JP4494977B2 (en) | 2002-12-17 | 2010-06-30 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | Humanized antibody (H14.18) of mouse 14.18 antibody that binds to GD2 and its IL-2 fusion protein |
US20050069521A1 (en) | 2003-08-28 | 2005-03-31 | Emd Lexigen Research Center Corp. | Enhancing the circulating half-life of interleukin-2 proteins |
CA2551915C (en) | 2003-12-30 | 2015-06-23 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Il-7 fusion proteins |
PT1699821E (en) | 2003-12-31 | 2012-08-23 | Merck Patent Gmbh | Fc-erythropoietin fusion protein with improved pharmacokinetics |
WO2005070967A2 (en) | 2004-01-22 | 2005-08-04 | Merck Patent Gmbh | Anti-cancer antibodies with reduced complement fixation |
US7670595B2 (en) | 2004-06-28 | 2010-03-02 | Merck Patent Gmbh | Fc-interferon-beta fusion proteins |
RU2437893C2 (en) | 2004-12-09 | 2011-12-27 | Мерк Патент Гмбх | Il-7 versions with low immunising capacity |
US20070104689A1 (en) | 2005-09-27 | 2007-05-10 | Merck Patent Gmbh | Compositions and methods for treating tumors presenting survivin antigens |
JP2009521912A (en) | 2005-12-30 | 2009-06-11 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | Anti-CD19 antibody with reduced immunogenicity |
JP2009521909A (en) | 2005-12-30 | 2009-06-11 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | Anti-IL-6 antibody that inhibits binding of IL-6 and IL-6Rα complex to gp130 |
PT1966238E (en) | 2005-12-30 | 2012-07-31 | Merck Patent Gmbh | Interleukin-12p40 variants with improved stability |
AU2007229698B9 (en) | 2006-03-24 | 2012-11-08 | Merck Patent Gmbh | Engineered heterodimeric protein domains |
JP2009542592A (en) | 2006-07-06 | 2009-12-03 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | Compositions and methods for enhancing the effectiveness of an IL-2-mediated immune response |
-
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- 2002-03-07 EP EP02717581A patent/EP1366067B1/en not_active Expired - Lifetime
- 2002-03-07 DK DK02717581.9T patent/DK1366067T3/en active
- 2002-03-07 KR KR1020087032161A patent/KR20090010127A/en not_active Application Discontinuation
-
2003
- 2003-10-06 ZA ZA200307792A patent/ZA200307792B/en unknown
-
2006
- 2006-07-19 US US11/489,653 patent/US8066994B2/en not_active Expired - Fee Related
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1991004329A1 (en) * | 1989-09-20 | 1991-04-04 | Abbott Laboratories | Method of producing fusion proteins |
WO1991013166A1 (en) * | 1990-03-02 | 1991-09-05 | Abbott Biotech, Inc. | Antibody constructs with enhanced binding affinity |
WO1999043713A1 (en) * | 1998-02-25 | 1999-09-02 | Lexigen Pharmaceuticals Corporation | Enhancing the circulating half-life of antibody-based fusion proteins |
WO2000069913A1 (en) * | 1999-05-19 | 2000-11-23 | Lexigen Pharmaceuticals Corp. | EXPRESSION AND EXPORT OF INTERFERON-ALPHA PROTEINS AS Fc FUSION PROTEINS |
Non-Patent Citations (3)
Title |
---|
GILLIES ET AL.: 'Improving the efficacy of antibody-interleukin 2 fusion proteins by reducing their interaction with Fc receptors' CANCER RESEARCH vol. 59, 01 May 1999, pages 2159 - 2166, XP002107035 * |
See also references of EP1366067A2 * |
STEVENSON ET AL.: 'Conjugation of human Fcgamma in closed-hinge or open-hinge configuration to Fab' gamma and analogous ligands' J. OF IMMUNOLOGY vol. 158, 1997, pages 2242 - 2250, XP002955118 * |
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Also Published As
Publication number | Publication date |
---|---|
BR0207854A (en) | 2004-08-24 |
CN1330664C (en) | 2007-08-08 |
KR100900176B1 (en) | 2009-06-02 |
PT1366067E (en) | 2012-11-29 |
CA2440221A1 (en) | 2002-09-19 |
KR20030092015A (en) | 2003-12-03 |
RU2003129528A (en) | 2005-04-10 |
EP1366067B1 (en) | 2012-09-26 |
KR20090010127A (en) | 2009-01-28 |
AU2002248571B2 (en) | 2007-01-18 |
WO2002072605A3 (en) | 2002-11-14 |
DK1366067T3 (en) | 2012-10-22 |
JP4234438B2 (en) | 2009-03-04 |
CA2440221C (en) | 2013-02-05 |
US20060263856A1 (en) | 2006-11-23 |
US20030044423A1 (en) | 2003-03-06 |
US8066994B2 (en) | 2011-11-29 |
US7148321B2 (en) | 2006-12-12 |
ES2393733T3 (en) | 2012-12-27 |
PL206701B1 (en) | 2010-09-30 |
EP1366067A4 (en) | 2005-07-20 |
CN1509293A (en) | 2004-06-30 |
JP2004525630A (en) | 2004-08-26 |
HUP0303428A2 (en) | 2004-01-28 |
EP1366067A2 (en) | 2003-12-03 |
MXPA03008031A (en) | 2003-12-04 |
PL366981A1 (en) | 2005-02-07 |
ZA200307792B (en) | 2004-07-06 |
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