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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- C12N15/09—Recombinant DNA-technology
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- C12N15/66—General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligation; Use of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
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Families Citing this family (133)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60327795D1 (de) | 2002-11-09 | 2009-07-09 | Immunocore Ltd | T zell rezeptor "display" |
| RS53984B1 (sr) | 2003-12-10 | 2015-10-30 | E. R. Squibb & Sons L.L.C. | Ip-10 antitela i njihove upotrebe |
| NZ547157A (en) | 2003-12-10 | 2009-07-31 | Medarex Inc | Interferon Alpha Antibodies and their uses |
| HUE035082T2 (en) | 2004-06-21 | 2018-05-02 | Squibb & Sons Llc | Interferon alpha receptor 1 antibodies and their use |
| RU2494107C2 (ru) | 2005-05-09 | 2013-09-27 | Оно Фармасьютикал Ко., Лтд. | Моноклональные антитела человека к белку программируемой смерти 1 (pd-1) и способы лечения рака с использованием анти-pd-1-антител самостоятельно или в комбинации с другими иммунотерапевтическими средствами |
| WO2007002223A2 (en) | 2005-06-20 | 2007-01-04 | Medarex, Inc. | Cd19 antibodies and their uses |
| 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 |
| RU2421464C2 (ru) | 2005-10-21 | 2011-06-20 | Новартис Аг | Человеческие антитела к il-13 и их терапевтическое применение |
| 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 |
| EP2057193B1 (en) | 2006-08-04 | 2013-12-18 | Novartis AG | Ephb3-specific antibody and uses thereof |
| TW200817437A (en) | 2006-08-11 | 2008-04-16 | Medarex Inc | Monoclonal antibodies against stromal cell derived factor-1 (SDF-1) |
| AR062435A1 (es) | 2006-08-18 | 2008-11-05 | Xoma Technology Ltd | Anticuerpo especifico prlr (receptor de prolactina) y sus usos |
| MX2009002418A (es) | 2006-09-05 | 2009-04-23 | Medarex Inc | Anticuerpos para las proteinas morfogenicas oseas y receptores de estas y metodos para su uso. |
| KR101722261B1 (ko) | 2006-10-02 | 2017-04-03 | 메다렉스, 엘.엘.시. | Cxcr4에 결합하는 인간 항체 및 이의 용도 |
| WO2008060814A2 (en) | 2006-10-19 | 2008-05-22 | Merck & Co., Inc. | ANTI-IL-13Rα1 ANTIBODIES AND THEIR USES THEREOF |
| 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 |
| KR20090088891A (ko) | 2006-11-15 | 2009-08-20 | 메다렉스, 인코포레이티드 | 비티엘에이에 대한 인간 단일클론 항체 및 이용 방법 |
| KR101552735B1 (ko) | 2006-12-01 | 2015-09-14 | 메다렉스, 엘.엘.시. | 씨디22에 결합하는 인간 항체 및 이의 용도 |
| KR101519672B1 (ko) | 2006-12-07 | 2015-05-29 | 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. |
| KR20090088946A (ko) | 2006-12-14 | 2009-08-20 | 메다렉스, 인코포레이티드 | 씨디70에 결합하는 인간 항체 및 이의 용도 |
| WO2009032845A2 (en) | 2007-09-04 | 2009-03-12 | Compugen, Ltd. | Polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics |
| 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 |
| KR20100091170A (ko) | 2007-11-02 | 2010-08-18 | 노파르티스 아게 | 저밀도-지단백질 수용체-관련 단백질 6 (lrp6)을 조정하기 위한 분자 및 방법 |
| KR101615935B1 (ko) | 2007-12-14 | 2016-04-28 | 노보 노르디스크 에이/에스 | 인간 nkg2d에 대한 항체 및 그것의 용도 |
| NZ587440A (en) | 2008-02-05 | 2013-01-25 | Pfizer | Antibodies specific for human integrin alpha 5 - beta 1 and their uses for treating tumours |
| PY09026846A (es) | 2008-08-05 | 2015-09-01 | Novartis Ag | Composiciones y métodos para anticuerpos que se dirigen a la proteína de complemento c5 |
| 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 |
| 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 |
| US8420084B2 (en) | 2009-03-05 | 2013-04-16 | Medarex, Inc. | Fully human antibodies specific to CADM1 |
| DK2421898T3 (en) | 2009-04-20 | 2016-05-30 | Oxford Biotherapeutics Ltd | Cadherin-17 SPECIFIC ANTIBODIES |
| JP5766179B2 (ja) | 2009-04-27 | 2015-08-19 | ノバルティス アーゲー | 筋肉増殖を増加させるための組成物および方法 |
| EP2424894A1 (en) | 2009-04-27 | 2012-03-07 | Novartis AG | Composition and methods of use for therapeutic antibodies specific for the il-12 receptore betal subunit |
| ES2652340T3 (es) * | 2009-07-17 | 2018-02-01 | Bioatla Llc | Selección y evolución simultáneas e integradas de rendimiento y expresión de proteínas humanas en huéspedes de producción |
| WO2011021146A1 (en) | 2009-08-20 | 2011-02-24 | Pfizer Inc. | Osteopontin antibodies |
| US8926976B2 (en) | 2009-09-25 | 2015-01-06 | Xoma Technology Ltd. | Modulators |
| CN102597775A (zh) | 2009-09-25 | 2012-07-18 | 佐马技术有限公司 | 筛选方法 |
| EP2470569A1 (en) | 2009-10-13 | 2012-07-04 | Oxford Biotherapeutics Ltd. | Antibodies against epha10 |
| WO2011067711A2 (en) | 2009-12-01 | 2011-06-09 | Compugen Ltd | Novel 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 |
| BR112012024565B1 (pt) | 2010-03-26 | 2022-02-08 | Trustees Of Dartmouth College | Proteína de fusão vista imunossupressora multimérica isolada ou recombinante e composição |
| US20150231215A1 (en) | 2012-06-22 | 2015-08-20 | Randolph J. Noelle | VISTA Antagonist and Methods of Use |
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| WO2011163401A2 (en) | 2010-06-22 | 2011-12-29 | Neogenix Oncology, Inc. | Colon and pancreas cancer specific antigens and antibodies |
| CN103003696B (zh) * | 2010-07-16 | 2016-06-01 | 生物蛋白有限公司 | 蛋白演化的新方法 |
| BR112013002993A2 (pt) | 2010-08-09 | 2018-01-30 | Cyvax Inc | métodos e composições para prevenção de uma condição |
| NZ607337A (en) | 2010-08-20 | 2015-06-26 | 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 |
| WO2012040617A2 (en) | 2010-09-23 | 2012-03-29 | Neogenix Oncology, 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 |
| US20140038842A1 (en) | 2010-12-28 | 2014-02-06 | Xoma Technology | Cell surface display using pdz domains |
| BR112013026199A2 (pt) | 2011-04-15 | 2017-11-07 | Compugen Ltd | polipeptídeo isolado, proteína de fusão, sequência de ácidos nucleicos, vetor de expressão ou um vírus, célula recombinante, método de produção de um polipeptídeo com ectodomínio solúvel lsr, ou seu fragmento ou proteína de fusão, composição farmacêutica, uso de um anticorpo monoclonal ou policlonal ou um seu fragmento de ligação ao antígeno, uso do anticorpo ou do fragmento de ligação ao antígeno, uso de qualquer um de um polipeptídeo isolado, método de regulação por cima de citocinas, indução da expansão de células t, promoção da imunidade de células t específica antigênica e promoção da ativação das células t cd4+ e/ou cd8+ em um sujeito, método para potenciação de uma resposta imune secundária a um antígeno em um paciente, método de uso de pelo menos um de: um polipeptídeo isolado, método para tratamento ou prevenção de uma condição relacionada com o sistema imune, método para tratamento ou prevenção de uma doença infecciosa, método para diagnóstico de uma doença em um sujeito, método de produção de um polipeptídeo com ectodomínio solúvel tmem25, vsig10, ly6g6f, ou seu fragmento ou proteína de fusão, anticorpo monoclonal ou policlonal ou um seu fragmento de ligação ao antígeno, método de imunoterapia em um paciente e método para combinação de vacinação terapêutica com um antígeno em conjunto com a administração de qualquer um de um polipeptídeo |
| SG195253A1 (en) | 2011-06-03 | 2013-12-30 | 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 |
| UA114478C2 (uk) | 2011-06-28 | 2017-06-26 | Берлін-Хемі Аг | Антитіло, яке специфічно зв'язується з bst1 |
| WO2013001517A1 (en) | 2011-06-30 | 2013-01-03 | Compugen Ltd. | Polypeptides and uses thereof for treatment of autoimmune disorders and infection |
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| KR20140103135A (ko) | 2011-12-05 | 2014-08-25 | 노파르티스 아게 | Her3의 도메인 ii에 대해 지시된 표피 성장 인자 수용체 3 (her3)에 대한 항체 |
| AU2012349735B2 (en) | 2011-12-05 | 2016-05-19 | Novartis Ag | Antibodies for epidermal growth factor receptor 3 (HER3) |
| PE20150159A1 (es) | 2011-12-21 | 2015-02-08 | Novartis Ag | Composiciones y metodos para anticuerpos que actuan sobre el factor p |
| KR20140126357A (ko) | 2012-02-01 | 2014-10-30 | 컴퓨젠 엘티디. | C1orf32 항체 및 이의 암 치료를 위한 용도 |
| US9890215B2 (en) | 2012-06-22 | 2018-02-13 | King's College London | Vista modulators for diagnosis and 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 |
| JP6368308B2 (ja) | 2012-09-07 | 2018-08-01 | トラスティーズ・オブ・ダートマス・カレッジ | 癌の診断および治療のためのvista調節剤 |
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| EP2935589A1 (en) | 2012-12-18 | 2015-10-28 | Novartis AG | Compositions and methods that utilize a peptide tag that binds to hyaluronan |
| EP3336104A1 (en) | 2012-12-28 | 2018-06-20 | 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 |
| EP2970479B1 (en) | 2013-03-14 | 2019-04-24 | Novartis AG | Antibodies against notch 3 |
| 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 |
| KR20160042987A (ko) | 2013-08-14 | 2016-04-20 | 노파르티스 아게 | 산발성 봉입체 근염을 치료하는 방법 |
| RS63295B1 (sr) | 2013-12-24 | 2022-06-30 | Janssen Pharmaceutica Nv | Anti-vista antitela i fragmenti |
| 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. |
| WO2015198243A2 (en) | 2014-06-25 | 2015-12-30 | Novartis Ag | Compositions and methods for long acting proteins |
| EP3160991A2 (en) | 2014-06-25 | 2017-05-03 | 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 |
| 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 |
| MY189836A (en) | 2014-11-21 | 2022-03-11 | Bristol Myers Squibb Co | Antibodies against cd73 and uses thereof |
| JP2018505911A (ja) | 2014-12-05 | 2018-03-01 | イミュネクスト,インコーポレーテッド | 推定上のvista受容体としてのvsig8の同定と、vista/vsig8調節剤を産生するためのその使用 |
| UY36449A (es) | 2014-12-19 | 2016-07-29 | Novartis Ag | Composiciones y métodos para anticuerpos dirigidos a bmp6 |
| TN2019000101A1 (en) | 2015-05-29 | 2020-07-15 | Bristol Myers Squibb Co | Antibodies against ox40 and uses thereof. |
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Family Cites Families (5)
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| ES2078518T3 (es) * | 1990-04-05 | 1995-12-16 | Roberto Crea | Mutagenesis por desplazamiento completo. |
| 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 |
| CA2331335A1 (en) * | 1998-09-29 | 2000-04-06 | Maxygen, Inc. | Shuffling of codon altered genes |
| 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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- 2002-05-17 JP JP2002589648A patent/JP2004532038A/ja active Pending
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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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| EP1421203A4 (en) | 2005-06-01 |
| WO2002092780A3 (en) | 2004-03-25 |
| EP1421203A2 (en) | 2004-05-26 |
| WO2002092780A2 (en) | 2002-11-21 |
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