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 |
|---|---|---|---|---|
| AU2003276403B2 (en) | 2002-11-09 | 2010-04-15 | Adaptimmune Limited | T cell receptor display |
| AU2004299833B2 (en) | 2003-12-10 | 2009-05-07 | E. R. Squibb & Sons, L.L.C. | Interferon alpha antibodies and their uses |
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| RU2412202C2 (ru) | 2004-06-21 | 2011-02-20 | Медарекс, Инк. | Антитела рецептора 1 интерферона альфа и их применение |
| EP1896582A4 (en) | 2005-05-09 | 2009-04-08 | Ono Pharmaceutical Co | HUMAN MONOCLONAL ANTIBODIES AGAINST PROGRAMMED CELL DEATH 1 (PD-1) AND METHOD FOR CREATING TREATMENT WITH ANTI-PD-1 ANTIBODIES ALONE OR IN COMBINATION WITH OTHER IMMUNOTHERAPEUTICS |
| MX2007015944A (es) | 2005-06-20 | 2008-03-07 | Medarex Inc | Anticuerpos cd19 y sus usos. |
| CN104356236B (zh) | 2005-07-01 | 2020-07-03 | E.R.施贵宝&圣斯有限责任公司 | 抗程序性死亡配体1(pd-l1)的人单克隆抗体 |
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| CA2638902C (en) | 2005-12-08 | 2014-09-23 | Medarex, Inc. | Human monoclonal antibodies to fucosyl-gm1 and methods for using anti-fucosyl-gm1 antibodies |
| US8278421B2 (en) | 2006-03-20 | 2012-10-02 | Xoma Techolology Ltd. | Human antibodies specific for gastrin materials and methods |
| MX2009001341A (es) | 2006-08-04 | 2009-05-28 | Novartis Ag | Anticuerpos especificos de ephb3 y usos de los mismos. |
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| CN101627055A (zh) | 2006-09-05 | 2010-01-13 | 梅达雷克斯公司 | 骨形成蛋白及其受体的抗体以及它们的使用方法 |
| RS55740B1 (sr) | 2006-10-02 | 2017-07-31 | Squibb & Sons Inc | Humana antitela koja se vezuju za cxcr4 i njihove upotrebe |
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| 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. |
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| AR072999A1 (es) | 2008-08-11 | 2010-10-06 | Medarex Inc | Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos |
| 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 |
| PL2403878T3 (pl) | 2009-03-05 | 2017-12-29 | E. R. Squibb & Sons, L.L.C. | W pełni ludzkie przeciwciała specyficzne dla CADM1 |
| EP2421898B1 (en) | 2009-04-20 | 2016-03-16 | Oxford BioTherapeutics Ltd | Antibodies specific to cadherin-17 |
| DK2424895T3 (en) | 2009-04-27 | 2017-12-18 | Novartis Ag | Compositions and Methods for Increasing Muscle Growth |
| US8715657B2 (en) | 2009-04-27 | 2014-05-06 | Novartis Ag | Therapeutic antibodies binding IL12Rβ1 |
| DK3042957T3 (en) * | 2009-07-17 | 2018-01-02 | Bioatla Llc | At the same time, integrated selection and development of human 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 |
| WO2011038301A2 (en) | 2009-09-25 | 2011-03-31 | Xoma Technology Ltd. | Screening methods |
| US20120231004A1 (en) | 2009-10-13 | 2012-09-13 | Oxford Biotherapeutic Ltd. | Antibodies |
| WO2011067711A2 (en) | 2009-12-01 | 2011-06-09 | Compugen Ltd | Novel heparanase splice variant |
| US20150231215A1 (en) | 2012-06-22 | 2015-08-20 | Randolph J. Noelle | VISTA Antagonist and Methods of Use |
| EP2552947A4 (en) | 2010-03-26 | 2013-11-13 | Dartmouth College | VISTA REGULATORY T CELL MEDIATOR PROTEIN, VISTA BINDING ACTIVE SUBSTANCES AND USE THEREOF |
| US10745467B2 (en) | 2010-03-26 | 2020-08-18 | The Trustees Of Dartmouth College | VISTA-Ig for treatment of autoimmune, allergic and inflammatory disorders |
| CN103237811A (zh) | 2010-05-06 | 2013-08-07 | 诺瓦提斯公司 | 用于治疗性低密度脂蛋白相关蛋白质6(lrp6)多价抗体的组合物及使用方法 |
| 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) |
| CA2803391C (en) | 2010-06-22 | 2021-11-09 | Neogenix Oncology, Inc. | Npc1 antibodies that bind a muc5ac epitope |
| SG187033A1 (en) | 2010-07-16 | 2013-02-28 | Bioatla Llc | Novel methods of protein evolution |
| EP2603224A1 (en) | 2010-08-09 | 2013-06-19 | Cyvax, Inc. | Methods and compositions for preventing a condition |
| PH12013500333A1 (en) | 2010-08-20 | 2013-04-22 | Novartis Ag | Antibodies for epidermal growth factor receptor 3 (her3) |
| EP2616100B1 (en) | 2010-09-17 | 2016-08-31 | Compugen Ltd. | Compositions and methods for treatment of drug resistant multiple myeloma |
| CA3182320A1 (en) | 2010-09-23 | 2012-03-29 | Precision Biologics, Inc. | Colon and pancreas cancer peptidomimetics |
| EP2625203A1 (en) | 2010-10-05 | 2013-08-14 | Novartis AG | Anti-il12rbeta1 antibodies and their use in treating autoimmune and inflammatory disorders |
| EP2658971A1 (en) | 2010-12-28 | 2013-11-06 | XOMA Technology Ltd. | Cell surface display using pdz domains |
| SG194099A1 (en) | 2011-04-15 | 2013-11-29 | Compugen Ltd | Polypeptides and polynucleotides, and uses thereof for treatment of immune related disorders and cancer |
| BR112013030958B1 (pt) | 2011-06-03 | 2022-02-08 | Xoma Technology Ltd | Anticorpo que se liga ao fator de transformação de crescimento beta, composição farmacêutica, usos dos mesmos, molécula de ácido nucleico, vetor de expressão, e método para produção de um anticorpo |
| WO2012172495A1 (en) | 2011-06-14 | 2012-12-20 | Novartis Ag | Compositions and methods for antibodies targeting tem8 |
| BR112013032621A2 (pt) | 2011-06-28 | 2017-01-24 | Oxford Biotherapeutics Ltd | anticorpos |
| WO2013001517A1 (en) | 2011-06-30 | 2013-01-03 | Compugen Ltd. | Polypeptides and uses thereof for treatment of autoimmune disorders and infection |
| DK2726099T3 (en) | 2011-07-01 | 2018-11-05 | Novartis Ag | Method of treating metabolic disorders |
| JP2015500829A (ja) | 2011-12-05 | 2015-01-08 | ノバルティス アーゲー | 上皮細胞増殖因子受容体３（ｈｅｒ３）のドメインｉｉに対するｈｅｒ３の抗体 |
| ES2758433T3 (es) | 2011-12-05 | 2020-05-05 | Novartis Ag | Anticuerpos contra el receptor 3 del factor de crecimiento epidérmico (HER3) |
| CA2859493A1 (en) | 2011-12-21 | 2013-06-27 | Novartis Ag | Compositions and methods for antibodies targeting factor p |
| EP2756093A4 (en) | 2012-02-01 | 2015-07-01 | Compugen Ltd | C10RF32 ANTIBODIES AND USES THEREOF FOR THE TREATMENT OF CANCER |
| DK3421486T5 (da) | 2012-06-22 | 2024-09-16 | The Trustees Of Darthmouth College | Nye Vista-IG-konstruktioner og anvendelse af Vista-IG til behandling af autoimmune, allergiske og inflammatoriske lidelser |
| US9890215B2 (en) | 2012-06-22 | 2018-02-13 | King's College London | Vista modulators for diagnosis and treatment of cancer |
| CA2884704C (en) | 2012-09-07 | 2023-04-04 | Randolph J. Noelle | Vista modulators for diagnosis and treatment of cancer |
| CN104968678B (zh) | 2012-12-05 | 2018-12-11 | 诺华股份有限公司 | 靶向epo的抗体的组合物和方法 |
| MX2015007931A (es) | 2012-12-18 | 2015-10-05 | Novartis Ag | Composiciones y metodos que utilizan una etiqueta de peptido que se une a hialuronano. |
| NZ709828A (en) | 2012-12-28 | 2019-07-26 | Prec Biologics Inc | Humanized monoclonal antibodies and methods of use for the diagnosis and treatment of colon and pancreas cancer |
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| US9562101B2 (en) | 2013-06-21 | 2017-02-07 | Novartis Ag | Lectin-like oxidized LDL receptor 1 antibodies and methods of use |
| AR096601A1 (es) | 2013-06-21 | 2016-01-20 | Novartis Ag | Anticuerpos del receptor 1 de ldl oxidado similar a lectina y métodos de uso |
| CN105960414A (zh) | 2013-08-14 | 2016-09-21 | 诺华股份有限公司 | 治疗散发性包涵体肌炎的方法 |
| IL301714A (en) | 2013-12-24 | 2023-05-01 | Janssen Pharmaceutica Nv | Antibodies and anti-VISTA fragments |
| 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 |
| PT3151921T (pt) | 2014-06-06 | 2019-11-21 | Bristol Myers Squibb Co | Anticorpos contra recetor do fator de necrose tumoral induzido por glicocorticoide e utilizações dos mesmos |
| MX389695B (es) | 2014-06-11 | 2025-03-20 | Kathy A Green | Uso de agonistas y antagonistas vista para suprimir o aumentar la inmunidad humoral. |
| US20170327553A1 (en) | 2014-06-25 | 2017-11-16 | Novartis Ag | Compositions and methods for long acting proteins |
| WO2015198243A2 (en) | 2014-06-25 | 2015-12-30 | Novartis Ag | Compositions and methods for long acting proteins |
| US20170291939A1 (en) | 2014-06-25 | 2017-10-12 | Novartis Ag | Antibodies specific for il-17a fused to hyaluronan binding peptide tags |
| EP3194437B1 (en) | 2014-08-07 | 2021-01-20 | Novartis AG | Angiopoietin-like 4 (angptl4) antibodies and methods of use |
| AP2017009721A0 (en) | 2014-08-07 | 2017-01-31 | Novartis Ag | Angiopoietin-like 4 antibodies and methods of use |
| ES2807182T3 (es) | 2014-11-21 | 2021-02-22 | Bristol Myers Squibb Co | Anticuerpos frente a CD73 y sus usos |
| 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 |
| RS63897B1 (sr) | 2015-05-29 | 2023-02-28 | Bristol Myers Squibb Co | Antitela protiv ox40 i njihova primena |
| WO2016193872A2 (en) | 2015-06-05 | 2016-12-08 | Novartis Ag | Antibodies targeting bone morphogenetic protein 9 (bmp9) and methods therefor |
| CN114805576A (zh) | 2015-06-24 | 2022-07-29 | 詹森药业有限公司 | 抗vista抗体和片段 |
| JOP20200312A1 (ar) | 2015-06-26 | 2017-06-16 | Novartis Ag | الأجسام المضادة للعامل xi وطرق الاستخدام |
| EP3331914A1 (en) | 2015-08-03 | 2018-06-13 | Novartis AG | Methods of treating fgf21-associated disorders |
| KR20180042433A (ko) | 2015-09-09 | 2018-04-25 | 노파르티스 아게 | 흉선 기질 림포포이에틴 (tslp)-결합 항체 및 항체의 사용 방법 |
| UY36889A (es) | 2015-09-09 | 2017-04-28 | Novartis Ag | Moléculas de unión a linfopoyetina estromal timica (tslp) y métodos de uso de las moléculas |
| 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 |
| JP2019506844A (ja) | 2015-12-18 | 2019-03-14 | ノバルティス アーゲー | ＣＤ３２ｂを標的とする抗体およびその使用方法 |
| BR112018016461A2 (pt) | 2016-02-12 | 2019-10-01 | Janssen Pharmaceutica Nv | anticorpos e fragmentos anti-vista, usos dos mesmos e métodos de identificação dos mesmos |
| SG10201913033UA (en) | 2016-03-04 | 2020-03-30 | Bristol Myers Squibb Co | Combination therapy with anti-cd73 antibodies |
| CA3020848A1 (en) | 2016-04-15 | 2017-10-19 | Janssen Pharmaceuticals, Inc. | Anti-human vista antibodies and use thereof |
| JP7138567B2 (ja) | 2016-04-27 | 2022-09-16 | ノバルティス アーゲー | 成長分化因子１５に対する抗体およびそれらの使用 |
| 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 |
| CA3027651A1 (en) | 2016-06-15 | 2017-12-21 | Novartis Ag | Methods for treating disease using inhibitors of bone morphogenetic protein 6 (bmp6) |
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| 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 |
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| WO2020136218A1 (en) | 2018-12-26 | 2020-07-02 | Imcheck Therapeutics Sas | Btn3a binding proteins and uses thereof |
| CA3117619A1 (en) | 2019-01-02 | 2020-07-09 | Neuracle Science Co., Ltd. | Anti-family with sequence similarity 19, member a5 antibodies and method of use thereof |
| CN113396162B (zh) | 2019-01-22 | 2024-08-16 | 百时美施贵宝公司 | 抗IL-7Rα亚基的抗体及其用途 |
| JP2022548881A (ja) | 2019-09-18 | 2022-11-22 | ノバルティス アーゲー | Ｅｎｔｐｄ２抗体、組合せ療法並びに抗体及び組合せ療法を使用する方法 |
| TW202124446A (zh) | 2019-09-18 | 2021-07-01 | 瑞士商諾華公司 | 與ｅｎｔｐｄ２抗體之組合療法 |
| MX2023000547A (es) | 2020-07-16 | 2023-02-13 | Novartis Ag | Anticuerpos anti-betacelulina, fragmentos de los mismos, y moleculas de union multiespecificas. |
| US12018254B2 (en) * | 2020-07-27 | 2024-06-25 | Wisconsin Alumni Research Foundation | Methods of making unbiased phage libraries |
| WO2022212876A1 (en) | 2021-04-02 | 2022-10-06 | The Regents Of The University Of California | Antibodies against cleaved cdcp1 and uses thereof |
| JP2025516472A (ja) | 2022-05-10 | 2025-05-30 | イムチェック セラピューティクス エスエーエス | 胃腸炎症性障害を処置する方法における使用のための抗ｂｔｎ３ａ抗体 |
| 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)
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| JP4251406B2 (ja) * | 1990-04-05 | 2009-04-08 | クレア，ロベルト | ウォーク―スルー突然変異誘発 |
| 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 |
| KR20010085850A (ko) * | 1998-09-29 | 2001-09-07 | 추후제출 | 코돈 변형 유전자의 재편성 |
| JP2002537836A (ja) * | 1999-03-09 | 2002-11-12 | ディベルサ コーポレーション | 定方向進化におけるエンドセレクション |
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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 |
| WO2002092780A2 (en) | 2002-11-21 |
| EP1421203A4 (en) | 2005-06-01 |
| WO2002092780A3 (en) | 2004-03-25 |
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