JP2010515456A5 - - Google Patents
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- JP2010515456A5 JP2010515456A5 JP2009545591A JP2009545591A JP2010515456A5 JP 2010515456 A5 JP2010515456 A5 JP 2010515456A5 JP 2009545591 A JP2009545591 A JP 2009545591A JP 2009545591 A JP2009545591 A JP 2009545591A JP 2010515456 A5 JP2010515456 A5 JP 2010515456A5
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| US8128926B2 (en) | 2007-01-09 | 2012-03-06 | Biogen Idec Ma Inc. | Sp35 antibodies and uses thereof |
| CA2729961C (en) * | 2008-07-09 | 2018-05-01 | Biogen Idec Ma Inc. | Li113, li62 variant co2, anti-lingo antibodies |
| JP5730211B2 (ja) | 2008-11-20 | 2015-06-03 | バイオジェン アイデック エムエー インコーポレイティドＢｉｏｇｅｎ Ｉｄｅｃ Ｉｎｃ． | ウイルスのアルギニン不活化 |
| EP2483289B2 (en) | 2009-10-02 | 2025-03-26 | Biogen MA Inc. | Methods of preventing and removing trisulfide bonds |
| WO2012158551A1 (en) | 2011-05-13 | 2012-11-22 | Biogen Idec Ma Inc. | Methods of preventing and removing trisulfide bonds |
| UY34317A (es) * | 2011-09-12 | 2013-02-28 | Genzyme Corp | Anticuerpo antireceptor de célula T (alfa)/ß |
| KR102142161B1 (ko) | 2012-05-14 | 2020-08-06 | 바이오젠 엠에이 인코포레이티드 | 운동 뉴런 관련 병태 치료용 lingo-2 길항제 |
| US9790268B2 (en) | 2012-09-12 | 2017-10-17 | Genzyme Corporation | Fc containing polypeptides with altered glycosylation and reduced effector function |
| CA2887682A1 (en) * | 2012-10-09 | 2014-04-17 | Biogen Idec Ma Inc. | Combination therapies and uses for treatment of demyelinating disorders |
| US9701753B2 (en) | 2013-03-11 | 2017-07-11 | Genzyme Corporation | Hyperglycosylated binding polypeptides |
| WO2015057939A1 (en) | 2013-10-18 | 2015-04-23 | Biogen Idec Ma Inc. | Anti-s1p4 antibodies and uses thereof |
| MX384246B (es) | 2013-10-30 | 2025-03-14 | Genzyme Corp | POLIPÉPTIDO DE UNIÓN A TCR ALFA BETA PARA USARSE EN LA DISMINUCIÓN DE LINFOCITOS TAß. |
| WO2015143091A1 (en) | 2014-03-19 | 2015-09-24 | Genzyme Corporation | Site-specific glycoengineering of targeting moieties |
| CA3205824A1 (en) | 2014-10-09 | 2016-04-14 | Genzyme Corporation | Glycoengineered antibody drug conjugates |
| JP2018504400A (ja) | 2015-01-08 | 2018-02-15 | バイオジェン・エムエイ・インコーポレイテッドＢｉｏｇｅｎ ＭＡ Ｉｎｃ． | Ｌｉｎｇｏ‐１拮抗薬及び脱髄障害の治療のための使用 |
| AU2016270373A1 (en) | 2015-06-05 | 2018-01-04 | Vertex Pharmaceuticals Incorporated | Triazoles for the treatment of demyelinating diseases |
| KR20190039134A (ko) * | 2016-07-13 | 2019-04-10 | 바이오젠 엠에이 인코포레이티드 | Lingo-1 길항제의 투약 섭생 및 탈수초성 질환의 치료를 위한 용도 |
| WO2018106646A1 (en) | 2016-12-06 | 2018-06-14 | Vertex Pharmaceuticals Incorporated | Aminotriazoles for the treatment of demyelinating diseases |
| WO2018106643A1 (en) | 2016-12-06 | 2018-06-14 | Vertex Pharmaceuticals Incorporated | Heterocyclic azoles for the treatment of demyelinating diseases |
| WO2018106641A1 (en) | 2016-12-06 | 2018-06-14 | Vertex Pharmaceuticals Incorporated | Pyrazoles for the treatment of demyelinating diseases |
| US20200031895A1 (en) | 2016-12-16 | 2020-01-30 | Biogen Ma Inc. | Stabilized proteolytically activated growth differentiation factor 11 |
| CN111201030B (zh) | 2017-07-25 | 2024-11-01 | 真和制药有限公司 | 通过阻断tim-3和其配体的相互作用治疗癌症 |
| WO2020160156A2 (en) | 2019-01-30 | 2020-08-06 | Immutics, Inc. | Anti-gal3 antibodies and uses thereof |
| WO2020190104A1 (ko) * | 2019-03-20 | 2020-09-24 | 주식회사 굳티셀 | 뇌신경계 질환의 예방 또는 치료용 조성물 |
| CN120192414A (zh) | 2019-04-03 | 2025-06-24 | 建新公司 | 具有降低的断裂的抗αβTCR结合多肽 |
| EP4157338A4 (en) | 2020-05-26 | 2024-11-13 | TrueBinding, Inc. | METHOD FOR TREATING INFLAMMATORY DISEASES BY GALECTIN-3 BLOCKING |
| US11124568B1 (en) * | 2020-08-19 | 2021-09-21 | Vitruviae LLC | CD3/CD25 antibodies for neuro-immune diseases |
| US11197910B1 (en) | 2020-08-19 | 2021-12-14 | Vitruviae LLC | Fusion proteins for the diagnosis, prophylaxis and treatment of infectious diseases |
| KR20230119179A (ko) * | 2020-12-10 | 2023-08-16 | 우시 바이올로직스 아일랜드 리미티드 | P-캐드히린에 대한 항체 및 이의 용도 |
| CN114805579B (zh) * | 2022-06-08 | 2023-06-06 | 郑州大学 | 一种抗人ace2蛋白单克隆抗体、核酸分子及应用 |
Family Cites Families (105)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773319A (en) | 1971-12-16 | 1973-11-20 | Fabcor Ind Inc | Corrugated sheet inverting machine |
| US4444887A (en) | 1979-12-10 | 1984-04-24 | Sloan-Kettering Institute | Process for making human antibody producing B-lymphocytes |
| IE52535B1 (en) | 1981-02-16 | 1987-12-09 | Ici Plc | Continuous release pharmaceutical compositions |
| US4474893A (en) | 1981-07-01 | 1984-10-02 | The University of Texas System Cancer Center | Recombinant monoclonal antibodies |
| US4714681A (en) | 1981-07-01 | 1987-12-22 | The Board Of Reagents, The University Of Texas System Cancer Center | Quadroma cells and trioma cells and methods for the production of same |
| US4716111A (en) | 1982-08-11 | 1987-12-29 | Trustees Of Boston University | Process for producing human antibodies |
| US4741900A (en) | 1982-11-16 | 1988-05-03 | Cytogen Corporation | Antibody-metal ion complexes |
| GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| 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 |
| US4694778A (en) | 1984-05-04 | 1987-09-22 | Anicon, Inc. | Chemical vapor deposition wafer boat |
| 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 |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| EP0216846B2 (en) | 1985-04-01 | 1995-04-26 | Celltech Limited | Transformed myeloma cell-line and a process for the expression of a gene coding for a eukaryotic polypeptide employing same |
| GB8601597D0 (en) | 1986-01-23 | 1986-02-26 | Wilson R H | Nucleotide sequences |
| 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 |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
| US5892019A (en) | 1987-07-15 | 1999-04-06 | The United States Of America, As Represented By The Department Of Health And Human Services | Production of a single-gene-encoded immunoglobulin |
| GB8717430D0 (en) | 1987-07-23 | 1987-08-26 | Celltech Ltd | Recombinant dna product |
| AU631802B2 (en) | 1988-06-14 | 1992-12-10 | Cetus Oncology Corporation | Coupling agents and sterically hindered disulfide linked conjugates prepared therefrom |
| US4925648A (en) | 1988-07-29 | 1990-05-15 | Immunomedics, Inc. | Detection and treatment of infectious and inflammatory lesions |
| US5601819A (en) | 1988-08-11 | 1997-02-11 | The General Hospital Corporation | Bispecific antibodies for selective immune regulation and for selective immune cell binding |
| EP0436597B1 (en) | 1988-09-02 | 1997-04-02 | Protein Engineering Corporation | Generation and selection of recombinant varied binding proteins |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| EP0368684B2 (en) | 1988-11-11 | 2004-09-29 | Medical Research Council | Cloning immunoglobulin variable domain sequences. |
| US5175384A (en) | 1988-12-05 | 1992-12-29 | Genpharm International | Transgenic mice depleted in mature t-cells and methods for making transgenic mice |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5225538A (en) | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
| US5116964A (en) | 1989-02-23 | 1992-05-26 | Genentech, Inc. | Hybrid immunoglobulins |
| IE63847B1 (en) | 1989-05-05 | 1995-06-14 | Res Dev Foundation | A novel antibody delivery system for biological response modifiers |
| ES2096590T3 (es) | 1989-06-29 | 1997-03-16 | Medarex Inc | Reactivos biespecificos para la terapia del sida. |
| US5413923A (en) | 1989-07-25 | 1995-05-09 | Cell Genesys, Inc. | Homologous recombination for universal donor cells and chimeric mammalian hosts |
| GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
| AU7247191A (en) | 1990-01-11 | 1991-08-05 | Molecular Affinities Corporation | Production of antibodies using gene libraries |
| US5780225A (en) | 1990-01-12 | 1998-07-14 | Stratagene | Method for generating libaries of antibody genes comprising amplification of diverse antibody DNAs and methods for using these libraries for the production of diverse antigen combining molecules |
| US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| DE69120146T2 (de) | 1990-01-12 | 1996-12-12 | Cell Genesys Inc | Erzeugung xenogener antikörper |
| WO1996033735A1 (en) | 1995-04-27 | 1996-10-31 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US5314995A (en) | 1990-01-22 | 1994-05-24 | Oncogen | Therapeutic interleukin-2-antibody based fusion proteins |
| WO1991014438A1 (en) | 1990-03-20 | 1991-10-03 | The Trustees Of Columbia University In The City Of New York | Chimeric antibodies with receptor binding ligands in place of their constant region |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| US5219837A (en) | 1990-06-21 | 1993-06-15 | Trustees Of The University Of Pennsylvania | Method of stimulating myelination of cells |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| ATE158021T1 (de) | 1990-08-29 | 1997-09-15 | Genpharm Int | Produktion und nützung nicht-menschliche transgentiere zur produktion heterologe antikörper |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5698426A (en) | 1990-09-28 | 1997-12-16 | Ixsys, Incorporated | Surface expression libraries of heteromeric receptors |
| DK0553244T4 (da) | 1990-10-05 | 2005-08-01 | Celldex Therapeutics Inc | Målrettet immunostimulering med bispecifikke reagenser |
| WO1992008802A1 (en) | 1990-10-29 | 1992-05-29 | Cetus Oncology Corporation | Bispecific antibodies, method of production, and uses thereof |
| DE69133036T2 (de) | 1990-11-09 | 2003-02-06 | Stephen D. Gillies | Cytokine immunokonjugate |
| CA2095633C (en) | 1990-12-03 | 2003-02-04 | Lisa J. Garrard | Enrichment method for variant proteins with altered binding properties |
| ATE414768T1 (de) | 1991-04-10 | 2008-12-15 | Scripps Research Inst | Bibliotheken heterodimerer rezeptoren mittels phagemiden |
| CA2108451A1 (en) | 1991-04-26 | 1992-10-27 | Beverley J. Randle | Novel antibodies, and methods for their use |
| EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
| EP1400536A1 (en) | 1991-06-14 | 2004-03-24 | Genentech Inc. | Method for making humanized antibodies |
| WO1992022324A1 (en) | 1991-06-14 | 1992-12-23 | Xoma Corporation | Microbially-produced antibody fragments and their conjugates |
| US5756096A (en) | 1991-07-25 | 1998-05-26 | Idec Pharmaceuticals Corporation | Recombinant antibodies for human therapy |
| MX9204374A (es) | 1991-07-25 | 1993-03-01 | Idec Pharma Corp | Anticuerpo recombinante y metodo para su produccion. |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| PT1024191E (pt) | 1991-12-02 | 2008-12-22 | Medical Res Council | Produção de auto-anticorpos a partir de reportórios de segmentos de anticorpo e exibidos em fagos |
| WO1993016177A1 (en) | 1992-02-11 | 1993-08-19 | Cell Genesys, Inc. | Homogenotization of gene-targeting events |
| PT627940E (pt) | 1992-03-05 | 2003-07-31 | Univ Texas | Utilizacao de imunoconjugados para o diagnostico e/ou terapia de tumores vascularizados |
| US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
| US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
| EP0627932B1 (en) | 1992-11-04 | 2002-05-08 | City Of Hope | Antibody construct |
| ATE236987T1 (de) | 1992-11-13 | 2003-04-15 | Idec Pharma Corp | Konsensus-kozak-sequenzen zur säugetier- exprimierung |
| US5736137A (en) | 1992-11-13 | 1998-04-07 | Idec Pharmaceuticals Corporation | Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma |
| WO1995015982A2 (en) | 1993-12-08 | 1995-06-15 | Genzyme Corporation | Process for generating specific antibodies |
| DE69534347T2 (de) | 1994-01-31 | 2006-05-24 | Trustees Of Boston University, Boston | Bibliotheken aus Polyklonalen Antikörpern |
| US5516637A (en) | 1994-06-10 | 1996-05-14 | Dade International Inc. | Method involving display of protein binding pairs on the surface of bacterial pili and bacteriophage |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| US6130364A (en) | 1995-03-29 | 2000-10-10 | Abgenix, Inc. | Production of antibodies using Cre-mediated site-specific recombination |
| WO1996034096A1 (en) | 1995-04-28 | 1996-10-31 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US5811524A (en) | 1995-06-07 | 1998-09-22 | Idec Pharmaceuticals Corporation | Neutralizing high affinity human monoclonal antibodies specific to RSV F-protein and methods for their manufacture and therapeutic use thereof |
| US6068829A (en) | 1995-09-11 | 2000-05-30 | The Burnham Institute | Method of identifying molecules that home to a selected organ in vivo |
| GB9524973D0 (en) | 1995-12-06 | 1996-02-07 | Lynxvale Ltd | Viral vectors |
| JP2978435B2 (ja) | 1996-01-24 | 1999-11-15 | チッソ株式会社 | アクリロキシプロピルシランの製造方法 |
| US6420140B1 (en) | 1996-10-11 | 2002-07-16 | Abgenix, Inc. | Production of multimeric protein by cell fusion method |
| US5916771A (en) | 1996-10-11 | 1999-06-29 | Abgenix, Inc. | Production of a multimeric protein by cell fusion method |
| CA2722378C (en) | 1996-12-03 | 2015-02-03 | Amgen Fremont Inc. | Human antibodies that bind tnf.alpha. |
| AU737155B2 (en) | 1997-03-14 | 2001-08-09 | Biogen Idec Inc. | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same |
| BRPI9809391B8 (pt) | 1997-04-14 | 2021-05-25 | Amgen Res Munich Gmbh | processo para a produção de um receptor de antígeno anti-humano, anticorpo humano e composição farmacêutica |
| US20030207346A1 (en) | 1997-05-02 | 2003-11-06 | William R. Arathoon | Method for making multispecific antibodies having heteromultimeric and common components |
| US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
| EP0983303B1 (en) | 1997-05-21 | 2006-03-08 | Biovation Limited | Method for the production of non-immunogenic proteins |
| WO1999004705A1 (en) | 1997-07-25 | 1999-02-04 | Tsui Ban C H | Devices, systems and methods for determining proper placement of epidural catheters |
| AU776910B2 (en) | 1998-12-08 | 2004-09-23 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Modifying protein immunogenicity |
| US6897044B1 (en) | 1999-01-28 | 2005-05-24 | Biogen Idec, Inc. | Production of tetravalent antibodies |
| US20020102208A1 (en) | 1999-03-01 | 2002-08-01 | Paul Chinn | Radiolabeling kit and binding assay |
| AU2001297872B2 (en) | 2000-11-17 | 2006-11-09 | University Of Rochester | In vitro methods of producing and identifying immunoglobulin molecules in eukaryotic cells |
| WO2002096948A2 (en) | 2001-01-29 | 2002-12-05 | Idec Pharmaceuticals Corporation | Engineered tetravalent antibodies and methods of use |
| NZ527283A (en) | 2001-01-29 | 2006-03-31 | Biogen Idec Inc | Modified antibodies and methods of use |
| US20030157641A1 (en) | 2001-11-16 | 2003-08-21 | Idec Pharmaceuticals Corporation | Polycistronic expression of antibodies |
| CA2519227C (en) | 2003-03-19 | 2013-12-03 | Biogen Idec Ma Inc. | Nogo receptor binding protein |
| AU2004266159A1 (en) * | 2003-08-22 | 2005-03-03 | Biogen Idec Ma Inc. | Improved antibodies having altered effector function and methods for making the same |
| US8486893B2 (en) * | 2004-06-24 | 2013-07-16 | Biogen Idec Ma Inc. | Treatment of conditions involving demyelination |
| KR100694862B1 (ko) | 2004-07-20 | 2007-03-13 | (주)인텔리안테크놀로지스 | 위성 안테나의 광대역 위성 탐색 장치 및 방법 |
| HRP20131066T1 (hr) * | 2005-07-08 | 2013-12-06 | Biogen Idec Ma Inc. | Sp35 antitijela i njihova upotreba |
| CA2729961C (en) * | 2008-07-09 | 2018-05-01 | Biogen Idec Ma Inc. | Li113, li62 variant co2, anti-lingo antibodies |
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