JP2004532038A - 新規抗原結合分子の治療、診断、予防、酵素、産業ならびに農業各分野への応用とそのための新規抗原結合分子の作製とスクリーニングの方法 - Google Patents
新規抗原結合分子の治療、診断、予防、酵素、産業ならびに農業各分野への応用とそのための新規抗原結合分子の作製とスクリーニングの方法 Download PDFInfo
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Families Citing this family (133)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1558643E (pt) * | 2002-11-09 | 2009-08-24 | Immunocore Ltd | Apresentação de um receptor das células t |
| DK1711207T3 (da) | 2003-12-10 | 2013-03-11 | Medarex Inc | Interferon-alpha-antistoffer og anvendelse heraf |
| ZA200604620B (en) | 2003-12-10 | 2007-10-31 | Medarex Inc | IP-10 antibodies and their uses |
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| JP5215180B2 (ja) | 2005-06-20 | 2013-06-19 | メダレックス インコーポレーティッド | Cd19抗体およびその使用法 |
| KR101411165B1 (ko) | 2005-07-01 | 2014-06-25 | 메다렉스, 엘.엘.시. | 예정 사멸 리간드 1 (피디-엘1)에 대한 인간 모노클로날항체 |
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| WO2007067992A2 (en) | 2005-12-08 | 2007-06-14 | Medarex, Inc. | Human monoclonal antibodies to fucosyl-gm1 and methods for using anti-fucosyl-gm1 |
| WO2007111661A2 (en) | 2006-03-20 | 2007-10-04 | Xoma Technology Ltd. | Human antibodies specific for gastrin materials and methods |
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| EP3018144A1 (en) | 2006-08-18 | 2016-05-11 | XOMA Technology Ltd. | Prlr-specific antibody and uses thereof |
| WO2008030611A2 (en) | 2006-09-05 | 2008-03-13 | Medarex, Inc. | Antibodies to bone morphogenic proteins and receptors therefor and methods for their use |
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| PL2068922T3 (pl) | 2006-10-19 | 2012-11-30 | Csl Ltd | Przeciwciała anty-IL-13R alfa1 i ich zastosowania |
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| CA2669921A1 (en) | 2006-11-15 | 2008-06-26 | Medarex, Inc. | Human monoclonal antibodies to btla and methods of use |
| CN103172743B (zh) | 2006-12-01 | 2015-04-08 | 梅达雷克斯有限责任公司 | 结合cd22的人抗体及其用途 |
| KR20140119831A (ko) | 2006-12-07 | 2014-10-10 | 노파르티스 아게 | Ephb3에 대한 길항제 항체 |
| CL2007003622A1 (es) | 2006-12-13 | 2009-08-07 | Medarex Inc | Anticuerpo monoclonal humano anti-cd19; composicion que lo comprende; y metodo de inhibicion del crecimiento de celulas tumorales. |
| US20100150950A1 (en) | 2006-12-14 | 2010-06-17 | Medarex, Inc. | Human antibodies that bind cd70 and uses thereof |
| ES2537580T3 (es) | 2007-09-04 | 2015-06-09 | Compugen Ltd. | Polipéptidos y polinucleótidos, y usos de los mismos como una diana farmacológica para producir fármacos y agentes biológicos |
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| WO2010067308A2 (en) | 2008-12-08 | 2010-06-17 | Compugen Ltd. | Polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics |
| BRPI1009232B1 (pt) | 2009-03-05 | 2022-05-03 | E.R. Squibb & Sons, Llc. | Anticorpo monoclonal isolado ou uma porção de ligação de antígeno do mesmo, ou um fragmento de anticorpo, composição que os compreende, molécula de ácido nucleico, hibridoma e métodos para a preparação de um anticorpo anti-cadm1 |
| US9181339B2 (en) | 2009-04-20 | 2015-11-10 | Oxford Bio Therapeutics Ltd. | Antibodies specific to cadherin-17 |
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| NO2424895T3 (enExample) | 2009-04-27 | 2018-02-03 | ||
| CN102625848A (zh) * | 2009-07-17 | 2012-08-01 | 生物蛋白有限公司 | 在生产宿主中同时整合抗体/蛋白的性能和表达的筛选和演化的方法 |
| WO2011021146A1 (en) | 2009-08-20 | 2011-02-24 | Pfizer Inc. | Osteopontin antibodies |
| EP3187877A1 (en) | 2009-09-25 | 2017-07-05 | XOMA Technology Ltd. | Screening methods |
| US8926976B2 (en) | 2009-09-25 | 2015-01-06 | Xoma Technology Ltd. | Modulators |
| US20120231004A1 (en) | 2009-10-13 | 2012-09-13 | Oxford Biotherapeutic Ltd. | Antibodies |
| US9428586B2 (en) | 2009-12-01 | 2016-08-30 | Compugen Ltd | Heparanase splice variant |
| US10745467B2 (en) | 2010-03-26 | 2020-08-18 | The Trustees Of Dartmouth College | VISTA-Ig for treatment of autoimmune, allergic and inflammatory disorders |
| US20150231215A1 (en) | 2012-06-22 | 2015-08-20 | Randolph J. Noelle | VISTA Antagonist and Methods of Use |
| CA2794483C (en) | 2010-03-26 | 2020-07-07 | Trustees Of Dartmouth College | Vista regulatory t cell mediator protein, vista binding agents and use thereof |
| ES2659406T3 (es) | 2010-05-06 | 2018-03-15 | Novartis Ag | Composiciones y procedimientos de uso para anticuerpos terapéuticos contra la proteína 6 relacionada con las lipoproteínas de baja densidad (LRP6) |
| US9290573B2 (en) | 2010-05-06 | 2016-03-22 | Novartis Ag | Therapeutic low density lipoprotein-related protein 6 (LRP6) multivalent antibodies |
| EP3327035A1 (en) | 2010-06-22 | 2018-05-30 | Precision Biologics Inc. | Colon and pancreas cancer specific antigens and antibodies |
| ES2966088T3 (es) * | 2010-07-16 | 2024-04-18 | Bioatla Inc | Nuevos métodos de evolución de proteínas |
| JP2013540700A (ja) | 2010-08-09 | 2013-11-07 | サイバツクス・インコーポレイテツド | 病気を予防するための方法および組成物 |
| PL2606070T3 (pl) | 2010-08-20 | 2017-06-30 | Novartis Ag | Przeciwciała dla receptora epidermalnego czynnika wzrostu 3 (her3) |
| WO2012035518A1 (en) | 2010-09-17 | 2012-03-22 | Compugen Ltd. | Compositions and methods for treatment of drug resistant multiple myeloma |
| WO2012040617A2 (en) | 2010-09-23 | 2012-03-29 | Neogenix Oncology, Inc. | Colon and pancreas cancer peptidomimetics |
| JP2013543384A (ja) | 2010-10-05 | 2013-12-05 | ノバルティス アーゲー | 抗−il12rベータ1抗体ならびに自己免疫性および炎症性疾患の処置おけるその使用 |
| US20140038842A1 (en) | 2010-12-28 | 2014-02-06 | Xoma Technology | Cell surface display using pdz domains |
| US9409987B2 (en) | 2011-04-15 | 2016-08-09 | Compugen Ltd | Polypeptides and polynucleotides, and uses thereof for treatment of immune related disorders and cancer |
| AU2012261933B2 (en) | 2011-06-03 | 2017-06-15 | Xoma Technology Ltd. | Antibodies specific for TGF-beta |
| WO2012172495A1 (en) | 2011-06-14 | 2012-12-20 | Novartis Ag | Compositions and methods for antibodies targeting tem8 |
| PL2726508T3 (pl) | 2011-06-28 | 2017-12-29 | Oxford Biotherapeutics Ltd | Przeciwciała przeciwko cyklazie ADP-rybozylowej 2 |
| EP2726503B1 (en) | 2011-06-30 | 2019-09-04 | Compugen Ltd. | Polypeptides and uses thereof for treatment of autoimmune disorders and infection |
| PL2726099T3 (pl) | 2011-07-01 | 2018-12-31 | Novartis Ag | Sposób leczenia zaburzeń metabolicznych |
| AU2012349735B2 (en) | 2011-12-05 | 2016-05-19 | Novartis Ag | Antibodies for epidermal growth factor receptor 3 (HER3) |
| EP2788382A2 (en) | 2011-12-05 | 2014-10-15 | Novartis AG | Antibodies for epidermal growth factor receptor 3 (her3) directed to domain ii of her3 |
| CA2859493A1 (en) | 2011-12-21 | 2013-06-27 | Novartis Ag | Compositions and methods for antibodies targeting factor p |
| KR20140126357A (ko) | 2012-02-01 | 2014-10-30 | 컴퓨젠 엘티디. | C1orf32 항체 및 이의 암 치료를 위한 용도 |
| TWI677507B (zh) | 2012-06-22 | 2019-11-21 | 達特茅斯學院基金會 | 新穎之vista-ig構築體及vista-ig用於治療自體免疫、過敏及發炎病症之用途 |
| US9890215B2 (en) | 2012-06-22 | 2018-02-13 | King's College London | Vista modulators for diagnosis and treatment of cancer |
| EP2892558B1 (en) | 2012-09-07 | 2019-04-10 | The Trustees Of Dartmouth College | Vista modulators for diagnosis and treatment of cancer |
| HRP20210517T1 (hr) | 2012-12-05 | 2021-05-14 | Novartis Ag | Pripravci i postupci za protutijela usmjerena na epo |
| KR20150095684A (ko) | 2012-12-18 | 2015-08-21 | 노파르티스 아게 | 히알루로난에 결합하는 펩티드 태그를 이용하는 조성물 및 방법 |
| WO2014106176A1 (en) | 2012-12-28 | 2014-07-03 | Precision Biologics, Inc. | Humanized monoclonal antibodies and methods of use for the diagnosis and treatment of colon and pancreas cancer |
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| WO2014159239A2 (en) | 2013-03-14 | 2014-10-02 | Novartis Ag | Antibodies against notch 3 |
| AR096601A1 (es) | 2013-06-21 | 2016-01-20 | Novartis Ag | Anticuerpos del receptor 1 de ldl oxidado similar a lectina y métodos de uso |
| US9562101B2 (en) | 2013-06-21 | 2017-02-07 | Novartis Ag | Lectin-like oxidized LDL receptor 1 antibodies and methods of use |
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| US11014987B2 (en) | 2013-12-24 | 2021-05-25 | Janssen Pharmaceutics Nv | Anti-vista antibodies and fragments, uses thereof, and methods of identifying same |
| TW201622746A (zh) | 2014-04-24 | 2016-07-01 | 諾華公司 | 改善或加速髖部骨折術後身體復原之方法 |
| DK3151921T3 (da) | 2014-06-06 | 2019-12-02 | Bristol Myers Squibb Co | Antistoffer mod glucocorticoid-induceret tumornekrosefaktor- receptorer (gitr) og anvendelser deraf |
| JP6997619B2 (ja) | 2014-06-11 | 2022-01-17 | キャシー・エイ・グリーン | 液性免疫の抑制または増進のための、vistaアゴニスト及びvistaアンタゴニストの使用 |
| US20170291939A1 (en) | 2014-06-25 | 2017-10-12 | Novartis Ag | Antibodies specific for il-17a fused to hyaluronan binding peptide tags |
| US20170290876A1 (en) | 2014-06-25 | 2017-10-12 | Novartis Ag | Compositions and methods for long acting proteins |
| WO2015198240A2 (en) | 2014-06-25 | 2015-12-30 | Novartis Ag | Compositions and methods for long acting proteins |
| WO2016020882A2 (en) | 2014-08-07 | 2016-02-11 | Novartis Ag | Angiopoetin-like 4 (angptl4) antibodies and methods of use |
| SG10201805646WA (en) | 2014-08-07 | 2018-08-30 | Novartis Ag | Angiopoietin-like 4 antibodies and methods of use |
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| AU2015357463B2 (en) | 2014-12-05 | 2021-10-07 | Immunext, Inc. | Identification of VSIG8 as the putative vista receptor and its use thereof to produce vista/VSIG8 modulators |
| UY36449A (es) | 2014-12-19 | 2016-07-29 | Novartis Ag | Composiciones y métodos para anticuerpos dirigidos a bmp6 |
| LT3303396T (lt) | 2015-05-29 | 2023-01-10 | Bristol-Myers Squibb Company | Antikūnai prieš ox40 ir jų panaudojimo būdai |
| CA2982237A1 (en) | 2015-06-05 | 2016-12-08 | Novartis Ag | Antibodies targeting bone morphogenetic protein 9 (bmp9) and methods therefor |
| EP3722314A1 (en) | 2015-06-24 | 2020-10-14 | Janssen Pharmaceutica NV | Anti-vista antibodies and fragments |
| JOP20200312A1 (ar) | 2015-06-26 | 2017-06-16 | Novartis Ag | الأجسام المضادة للعامل xi وطرق الاستخدام |
| KR102728071B1 (ko) | 2015-08-03 | 2024-11-11 | 노파르티스 아게 | Fgf21-연관 장애를 치료하는 방법 |
| RS61763B1 (sr) | 2015-09-09 | 2021-05-31 | Novartis Ag | Antitela koja vezuju timusni stromalni limfopoetin (tslp) i metode za korišćenje antitela |
| MY186352A (en) | 2015-09-09 | 2021-07-15 | Novartis Ag | Thymic stromal lymphopoietin (tslp)-binding antibodies and methods of using the antibodies |
| BR112018010172A2 (pt) | 2015-11-19 | 2018-11-21 | Bristol Myers Squibb Co | anticorpos contra receptor de fator de necrose de tumor induzido por glicocorticoide (gitr) e usos dos mesmos |
| UY37030A (es) | 2015-12-18 | 2017-07-31 | Novartis Ag | Anticuerpos dirigidos a cd32b y métodos de uso de los mismos |
| MX2018009800A (es) | 2016-02-12 | 2018-11-09 | Janssen Pharmaceutica Nv | Anticuerpos y fragmentos anti-vista, usos de los mismos y procedimientos de identificacion de los mismos. |
| KR20180118725A (ko) | 2016-03-04 | 2018-10-31 | 브리스톨-마이어스 스큅 컴퍼니 | 항-cd73 항체와의 조합 요법 |
| EP3448412A4 (en) | 2016-04-15 | 2020-03-25 | Immunext Inc. | ANTI-HUMAN-VISTA ANTIBODIES AND USE THEREOF |
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| TW201802121A (zh) | 2016-05-25 | 2018-01-16 | 諾華公司 | 抗因子XI/XIa抗體之逆轉結合劑及其用途 |
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Family Cites Families (5)
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| EP0527809B1 (en) * | 1990-04-05 | 1995-08-16 | CREA, Roberto | Walk-through mutagenesis |
| US6335160B1 (en) * | 1995-02-17 | 2002-01-01 | Maxygen, Inc. | Methods and compositions for polypeptide engineering |
| US6238884B1 (en) * | 1995-12-07 | 2001-05-29 | Diversa Corporation | End selection in directed evolution |
| IL140441A0 (en) * | 1998-09-29 | 2002-02-10 | Maxygen Inc | Shuffling of codon altered genes |
| CA2361927A1 (en) * | 1999-03-09 | 2000-09-14 | Diversa Corporation | End selection in directed evolution |
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- 2002-05-17 WO PCT/US2002/015767 patent/WO2002092780A2/en not_active Ceased
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010008391A (ja) * | 2008-05-27 | 2010-01-14 | Toray Ind Inc | 分析用チップ |
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| EP1421203A2 (en) | 2004-05-26 |
| EP1421203A4 (en) | 2005-06-01 |
| WO2002092780A2 (en) | 2002-11-21 |
| WO2002092780A3 (en) | 2004-03-25 |
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