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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- C12N15/09—Recombinant DNA-technology
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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 |
| KR101225299B1 (ko) | 2003-12-10 | 2013-01-24 | 메다렉스, 인코포레이티드 | 인터페론 알파 항체 및 그의 용도 |
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| US7662381B2 (en) | 2004-06-21 | 2010-02-16 | Medarex, Inc. | Interferon alpha receptor 1 antibodies and their uses |
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| CA2611814A1 (en) | 2005-06-20 | 2007-01-04 | Medarex, Inc. | Cd19 antibodies and their uses |
| PT1907424E (pt) | 2005-07-01 | 2015-10-09 | Squibb & Sons Llc | Anticorpos monoclonais humanos para o ligando 1 de morte programada (pd-l1) |
| WO2007045477A2 (en) | 2005-10-21 | 2007-04-26 | Novartis Ag | Human antibodies against il-13 and therapeutic uses |
| US8383118B2 (en) | 2005-12-08 | 2013-02-26 | Medarex, Inc. | Human monoclonal antibodies to fucosyl-GM1 and methods for using anti-fucosyl-GM1 |
| JP2009529915A (ja) | 2006-03-20 | 2009-08-27 | ゾーマ テクノロジー リミテッド | ガストリン物質に対して特異的なヒト抗体および方法 |
| CA2659820A1 (en) | 2006-08-04 | 2008-02-14 | Novartis Ag | Ephb3-specific antibody and uses thereof |
| JP5244785B2 (ja) | 2006-08-11 | 2013-07-24 | 小野薬品工業株式会社 | ストローマ由来因子−1(sdf−1)に対するモノクローナル抗体 |
| AR064801A1 (es) | 2006-08-18 | 2009-04-29 | Xoma Technology Ltd | Anticuerpo especifico prlr (receptor de prolactina) y sus usos |
| CA2662350A1 (en) | 2006-09-05 | 2008-03-13 | Medarex, Inc. | Antibodies to bone morphogenic proteins and receptors therefor and methods for their use |
| MX2009003306A (es) | 2006-10-02 | 2009-04-23 | Medarex Inc | Anticuerpos humanos que se unen a cxcr4 y sus usos. |
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| US8618248B2 (en) | 2006-10-31 | 2013-12-31 | President And Fellows Of Harvard College | Phosphopeptide compositions and anti-phosphopeptide antibody compositions and methods of detecting phosphorylated peptides |
| EP2097447A4 (en) | 2006-11-15 | 2010-12-29 | Medarex Inc | HUMAN MONOCLONAL ANTIBODIES AGAINST BTLA AND METHODS OF USE |
| US8481683B2 (en) | 2006-12-01 | 2013-07-09 | Medarex, Inc. | Human antibodies that bind CD22 and uses thereof |
| WO2008070780A1 (en) | 2006-12-07 | 2008-06-12 | Novartis Ag | Antagonist antibodies against ephb3 |
| 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. |
| MX2009006277A (es) | 2006-12-14 | 2009-07-24 | Medarex Inc | Anticuerpos humanos que se enlazan a cd70 y usos de los mismos. |
| JP5607530B2 (ja) | 2007-09-04 | 2014-10-15 | コンピュゲン エルティーディー. | ポリペプチド並びにポリヌクレオチド、並びに薬剤および生物製剤生産のための薬剤標的としてのその利用 |
| TWI489993B (zh) | 2007-10-12 | 2015-07-01 | Novartis Ag | 骨硬化素(sclerostin)抗體組合物及使用方法 |
| BRPI0820327A2 (pt) | 2007-11-02 | 2020-10-06 | Novartis Ag | moléculas e métodos para modulação de proteína relacionada ao receptor de lipoproteína de baixa densidade 6 (lrp6) |
| AU2008337517B2 (en) | 2007-12-14 | 2014-06-26 | Novo Nordisk A/S | Antibodies against human NKG2D and uses thereof |
| EP2650017A3 (en) | 2008-02-05 | 2014-01-22 | Bristol-Myers Squibb Company | Alpha 5 - beta 1 antibodies and their uses |
| PY09026846A (es) | 2008-08-05 | 2015-09-01 | Novartis Ag | Composiciones y métodos para anticuerpos que se dirigen a la proteína de complemento c5 |
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| US20110311450A1 (en) | 2008-12-08 | 2011-12-22 | Zurit Levine | Polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics |
| CN102341412B (zh) | 2009-03-05 | 2018-01-05 | 梅达雷克斯有限责任公司 | 特异于cadm1 的全人抗体 |
| DK2421898T3 (en) | 2009-04-20 | 2016-05-30 | Oxford Biotherapeutics Ltd | Cadherin-17 SPECIFIC ANTIBODIES |
| PE20120532A1 (es) | 2009-04-27 | 2012-05-18 | Novartis Ag | ANTICUERPOS ANTI-ActRIIB |
| JP2012524524A (ja) | 2009-04-27 | 2012-10-18 | ノバルティス アーゲー | IL−12レセプターβ1サブユニットに特異的な治療用抗体の組成物および使用方法 |
| SG10201700096VA (en) | 2009-07-17 | 2017-02-27 | Bioatla Llc | Simultaneous, Integrated Selection And Evolution Of Antibody/Protein Performance And Expression In Production Hosts |
| WO2011021146A1 (en) | 2009-08-20 | 2011-02-24 | Pfizer Inc. | Osteopontin antibodies |
| US8926976B2 (en) | 2009-09-25 | 2015-01-06 | Xoma Technology Ltd. | Modulators |
| EP2480888B1 (en) | 2009-09-25 | 2016-11-30 | XOMA Technology Ltd. | Screening methods |
| EP2470569A1 (en) | 2009-10-13 | 2012-07-04 | Oxford Biotherapeutics Ltd. | Antibodies against epha10 |
| EP2507265B1 (en) | 2009-12-01 | 2016-05-11 | Compugen Ltd. | Antibody specific for heparanase splice variant T5 and its use. |
| 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 |
| MX374075B (es) | 2010-03-26 | 2025-03-05 | Dartmouth College | Proteina mediadora de celula t regulatoria vista, agentes de enlace de vista y uso de los mismos. |
| PH12012502193A1 (en) | 2010-05-06 | 2021-08-09 | Novartis Ag | Compositions and methods of use for therapeutic low density lipoprotein - related protein 6 (lrp6) multivalent antibodies |
| EP2566892B1 (en) | 2010-05-06 | 2017-12-20 | Novartis AG | Compositions and methods of use for therapeutic low density lipoprotein-related protein 6 (lrp6) antibodies |
| US20130189268A1 (en) | 2010-06-22 | 2013-07-25 | Precision Biologics, Inc. | Colon and pancreas cancer specific antigens and antibodies |
| ES2741175T3 (es) * | 2010-07-16 | 2020-02-10 | Bioatla Llc | Nuevos métodos de evolución de proteínas |
| US8557248B2 (en) | 2010-08-09 | 2013-10-15 | Cyvax, Inc. | Methods and compositions for treating malaria |
| AU2011290672B2 (en) | 2010-08-20 | 2015-07-09 | Novartis Ag | Antibodies for epidermal growth factor receptor 3 (HER3) |
| WO2012035518A1 (en) | 2010-09-17 | 2012-03-22 | Compugen Ltd. | Compositions and methods for treatment of drug resistant multiple myeloma |
| ES2719624T3 (es) | 2010-09-23 | 2019-07-11 | Prec Biologics Inc | Peptidomiméticos de cáncer de colon y de páncreas |
| EP2625203A1 (en) | 2010-10-05 | 2013-08-14 | Novartis AG | Anti-il12rbeta1 antibodies and their use in treating autoimmune and inflammatory disorders |
| JP2014504503A (ja) | 2010-12-28 | 2014-02-24 | ゾーマ テクノロジー リミテッド | Pdzドメインを用いた細胞表面提示 |
| NZ713461A (en) | 2011-04-15 | 2017-02-24 | Compugen Ltd | Polypeptides and polynucleotides, and uses thereof for treatment of immune related disorders and cancer |
| CN103732623B (zh) | 2011-06-03 | 2017-09-29 | 佐马技术有限公司 | 对TGF‑β具有特异性的抗体 |
| 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 |
| US9428574B2 (en) | 2011-06-30 | 2016-08-30 | Compugen Ltd. | Polypeptides and uses thereof for treatment of autoimmune disorders and infection |
| JP6472999B2 (ja) | 2011-07-01 | 2019-02-20 | ノバルティス アーゲー | 代謝障害を治療するための方法 |
| CN104105709A (zh) | 2011-12-05 | 2014-10-15 | 诺华股份有限公司 | 抗her3的结构域ii的表皮生长因子受体3(her3)抗体 |
| EP3590538A1 (en) | 2011-12-05 | 2020-01-08 | Novartis AG | Antibodies for epidermal growth factor receptor 3 (her3) |
| ES2728278T3 (es) | 2011-12-21 | 2019-10-23 | Novartis Ag | Composiciones que comprenden anticuerpos dirigidos al factor P y C5 |
| CA2848985A1 (en) | 2012-02-01 | 2013-08-08 | Compugen Ltd. | C10rf32 antibodies, and uses thereof for treatment of cancer |
| US9890215B2 (en) | 2012-06-22 | 2018-02-13 | King's College London | Vista modulators for diagnosis and treatment of cancer |
| JP6285923B2 (ja) | 2012-06-22 | 2018-02-28 | トラスティーズ・オブ・ダートマス・カレッジ | 新規VISTA−Igコンストラクト及び自己免疫、アレルギー性及び炎症性障害の処置のためのVISTA−Igの使用 |
| US9381244B2 (en) | 2012-09-07 | 2016-07-05 | King's College London | VISTA modulators for diagnosis and treatment of cancer |
| DK2928921T3 (da) | 2012-12-05 | 2021-04-19 | Novartis Ag | Sammensætninger og fremgangsmåder til antistoffer målrettet epo |
| TW201427989A (zh) | 2012-12-18 | 2014-07-16 | Novartis Ag | 長效性蛋白質之組合物及方法 |
| CA2896723C (en) | 2012-12-28 | 2024-02-13 | Precision Biologics, Inc. | Humanized monoclonal antibodies and methods of use for the diagnosis and treatment of colon and pancreas cancer |
| LT2953969T (lt) | 2013-02-08 | 2019-12-10 | Novartis Ag | Anti-il-17a antikūnai ir jų panaudojimas autoimuninių ir uždegiminių ligų gydymui |
| EP3611189A1 (en) | 2013-03-14 | 2020-02-19 | 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 |
| UY35620A (es) | 2013-06-21 | 2015-01-30 | Novartis Ag | Anticuerpos del receptor 1 de ldl oxidado similar a lectina y métodos de uso |
| HK1219280A1 (zh) | 2013-08-14 | 2017-03-31 | Novartis Ag | 治疗偶发性包涵体肌炎之方法 |
| US11014987B2 (en) | 2013-12-24 | 2021-05-25 | Janssen Pharmaceutics Nv | Anti-vista antibodies and fragments, uses thereof, and methods of identifying same |
| WO2015097536A2 (en) | 2013-12-24 | 2015-07-02 | Janssen Pharmaceutical Nv | Anti-vista antibodies and fragments |
| 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 |
| PE20170441A1 (es) | 2014-06-06 | 2017-04-26 | Bristol Myers Squibb Co | Anticuerpos contra el receptor del factor de necrosis tumoral inducido por glucocorticoides (gitr) y sus usos |
| US11123426B2 (en) | 2014-06-11 | 2021-09-21 | The Trustees Of Dartmouth College | Use of vista agonists and antagonists to suppress or enhance humoral immunity |
| US20170327553A1 (en) | 2014-06-25 | 2017-11-16 | Novartis Ag | Compositions and methods for long acting proteins |
| EP3161001A2 (en) | 2014-06-25 | 2017-05-03 | Novartis AG | Antibodies specific for il-17a fused to hyaluronan binding peptide tags |
| EP3160990A2 (en) | 2014-06-25 | 2017-05-03 | 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 |
| WO2016020880A2 (en) | 2014-08-07 | 2016-02-11 | Novartis Ag | Angiopoietin-like 4 antibodies and methods of use |
| AU2015349878A1 (en) | 2014-11-21 | 2017-05-25 | Bristol-Myers Squibb Company | Antibodies against CD73 and uses thereof |
| CA2969730A1 (en) | 2014-12-05 | 2016-06-09 | 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 |
| DK3303396T5 (da) | 2015-05-29 | 2024-10-07 | Bristol Myers Squibb Co | Antistoffer mod ox40 og anvendelser deraf |
| EP3303387A2 (en) | 2015-06-05 | 2018-04-11 | Novartis AG | Antibodies targeting bone morphogenetic protein 9 (bmp9) and methods therefor |
| CA2990360C (en) | 2015-06-24 | 2024-02-13 | Janssen Pharmaceutica Nv | Anti-vista antibodies and fragments |
| UY36751A (es) | 2015-06-26 | 2017-01-31 | Novartis Ag | Anticuerpos de factor xi y métodos de uso |
| US11236159B2 (en) | 2015-08-03 | 2022-02-01 | Novartis Ag | Methods of treating FGF21-associated disorders |
| HRP20210650T1 (hr) | 2015-09-09 | 2021-05-28 | Novartis Ag | Protutijela koja vežu timusni stromalni limfopoetin (tslp) i postupci uporabe protutijela |
| EA038332B1 (ru) | 2015-09-09 | 2021-08-10 | Новартис Аг | Молекулы, связывающиеся с тимусным стромальным лимфопоэтином (tslp), и способы применения таких молекул |
| AU2016356780A1 (en) | 2015-11-19 | 2018-06-28 | Bristol-Myers Squibb Company | Antibodies against glucocorticoid-induced tumor necrosis factor receptor (GITR) and uses thereof |
| RU2018126297A (ru) | 2015-12-18 | 2020-01-22 | Новартис Аг | Антитела, нацеленные на cd32b, и способы их применения |
| WO2017137830A1 (en) | 2016-02-12 | 2017-08-17 | Janssen Pharmaceutica Nv | Anti-vista (b7h5) antibodies |
| EP3423494A1 (en) | 2016-03-04 | 2019-01-09 | Bristol-Myers Squibb Company | Combination therapy with anti-cd73 antibodies |
| KR20230119259A (ko) | 2016-04-15 | 2023-08-16 | 이뮤넥스트, 인크. | 항-인간 vista 항체 및 이의 용도 |
| WO2017189724A1 (en) | 2016-04-27 | 2017-11-02 | Novartis Ag | Antibodies against growth differentiation factor 15 and uses thereof |
| 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 |
| AU2017283787B2 (en) | 2016-06-15 | 2020-09-17 | Novartis Ag | Methods for treating disease using inhibitors of bone morphogenetic protein 6 (BMP6) |
| CN109757103B (zh) | 2016-07-14 | 2024-01-02 | 百时美施贵宝公司 | 针对tim3的抗体及其用途 |
| WO2018027042A1 (en) | 2016-08-03 | 2018-02-08 | Bio-Techne Corporation | Identification of vsig3/vista as a novel immune checkpoint and use thereof for immunotherapy |
| JP7045724B2 (ja) | 2016-11-07 | 2022-04-01 | ニューラクル サイエンス カンパニー リミテッド | 配列類似性を持つ抗ファミリー19、メンバーa5抗体及びその用途 |
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| EP3898700A1 (en) | 2018-12-18 | 2021-10-27 | Novartis AG | Reversal binding agents for anti-factor xi/xia antibodies and uses thereof |
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| EP4189084A1 (en) * | 2020-07-27 | 2023-06-07 | Wisconsin Alumni Research Foundation | Methods of making unbiased phage libraries |
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| WO2025155877A2 (en) | 2024-01-18 | 2025-07-24 | The Regents Of The University Of California | Antibodies binding to pad4 and uses thereof |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CA2079802C (en) * | 1990-04-05 | 2001-09-18 | Roberto Crea | 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 |
| AU3879300A (en) * | 1999-03-09 | 2000-09-28 | Diversa Corporation | End selection in directed evolution |
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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 |
| WO2002092780A3 (en) | 2004-03-25 |
| EP1421203A4 (en) | 2005-06-01 |
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