CA2538895A1 - Factor ixa specific antibodies displaying factor viiia like activity - Google Patents
Factor ixa specific antibodies displaying factor viiia like activity Download PDFInfo
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- CA2538895A1 CA2538895A1 CA002538895A CA2538895A CA2538895A1 CA 2538895 A1 CA2538895 A1 CA 2538895A1 CA 002538895 A CA002538895 A CA 002538895A CA 2538895 A CA2538895 A CA 2538895A CA 2538895 A1 CA2538895 A1 CA 2538895A1
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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| US10/661,366 | 2003-09-12 | ||
| US10/661,366 US7297336B2 (en) | 2003-09-12 | 2003-09-12 | Factor IXa specific antibodies displaying factor VIIIa like activity |
| PCT/EP2004/009975 WO2005025615A2 (en) | 2003-09-12 | 2004-09-07 | FACTOR IXa SPECIFIC ANTIBODIES DISPLAYING FACTOR VIIIa LIKE ACTIVITY |
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| CA2538895A1 true CA2538895A1 (en) | 2005-03-24 |
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| CA002538895A Abandoned CA2538895A1 (en) | 2003-09-12 | 2004-09-07 | Factor ixa specific antibodies displaying factor viiia like activity |
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| EP (1) | EP1660536B1 (enExample) |
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| ES (1) | ES2320665T3 (enExample) |
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| AT411997B (de) * | 1999-09-14 | 2004-08-26 | Baxter Ag | Faktor ix/faktor ixa aktivierende antikörper und antikörper-derivate |
| US10011858B2 (en) | 2005-03-31 | 2018-07-03 | Chugai Seiyaku Kabushiki Kaisha | Methods for producing polypeptides by regulating polypeptide association |
| EP1876236B9 (en) * | 2005-04-08 | 2015-02-25 | Chugai Seiyaku Kabushiki Kaisha | Antibody substituting for function of blood coagulation factor viii |
| EP1760092A1 (en) * | 2005-08-26 | 2007-03-07 | Applied Research Systems ARS Holding N.V. | System for screening cells for high expression of a protein of interest |
| EP2006381B1 (en) | 2006-03-31 | 2016-02-03 | Chugai Seiyaku Kabushiki Kaisha | Method for controlling blood pharmacokinetics of antibodies |
| EP3345616A1 (en) | 2006-03-31 | 2018-07-11 | Chugai Seiyaku Kabushiki Kaisha | Antibody modification method for purifying bispecific antibody |
| ES2595638T3 (es) | 2007-09-26 | 2017-01-02 | Chugai Seiyaku Kabushiki Kaisha | Método para modificar el punto isoeléctrico de un anticuerpo mediante la sustitución de aminoácidos en una CDR |
| KR101398363B1 (ko) | 2010-11-17 | 2014-05-22 | 추가이 세이야쿠 가부시키가이샤 | 혈액응고 제viii 인자의 기능을 대체하는 기능을 갖는 다중특이성 항원 결합 분자 |
| CN104937423B (zh) * | 2012-09-28 | 2017-05-24 | 中外制药株式会社 | 凝血反应的评价方法 |
| DK3050896T3 (da) | 2013-09-27 | 2021-07-19 | Chugai Pharmaceutical Co Ltd | Fremgangsmåde til fremstilling af en polypeptid-heteromultimer |
| CA2939293C (en) * | 2014-03-11 | 2023-10-03 | The Board Of Trustees Of The Leland Standford Junior University | Anti sirp-alpha antibodies and bi-specific macrophage enhancing antibodies |
| MA40764A (fr) | 2014-09-26 | 2017-08-01 | Chugai Pharmaceutical Co Ltd | Agent thérapeutique induisant une cytotoxicité |
| TWI701435B (zh) | 2014-09-26 | 2020-08-11 | 日商中外製藥股份有限公司 | 測定ｆｖｉｉｉ的反應性之方法 |
| TWI700300B (zh) | 2014-09-26 | 2020-08-01 | 日商中外製藥股份有限公司 | 中和具有第ｖｉｉｉ凝血因子（ｆｖｉｉｉ）機能替代活性的物質之抗體 |
| JP7082484B2 (ja) | 2015-04-01 | 2022-06-08 | 中外製薬株式会社 | ポリペプチド異種多量体の製造方法 |
| US20200270363A1 (en) | 2015-12-25 | 2020-08-27 | Chugai Seiyaku Kabushiki Kaisha | Antibody having enhanced activity, and method for modifying same |
| MX2018007781A (es) | 2015-12-28 | 2018-09-05 | Chugai Pharmaceutical Co Ltd | Metodo para promover la eficiencia de purificacion del polipeptido que contiene la region de fragmento cristalizable (fc). |
| BR112018067792A2 (pt) | 2016-04-28 | 2019-02-12 | Chugai Seiyaku Kabushiki Kaisha | preparação contendo o anticorpo |
| KR102625416B1 (ko) * | 2016-05-16 | 2024-01-15 | 다케다 파머수티컬 컴패니 리미티드 | 항-인자 ix 파두아 항체 |
| CA3035327A1 (en) | 2016-09-06 | 2018-03-15 | Chugai Seiyaku Kabushiki Kaisha | Methods of using a bispecific antibody that recognizes coagulation factor ix and/or activated coagulation factor ix and coagulation factor x and/or activated coagulation factor x |
| US20190248920A1 (en) * | 2016-09-23 | 2019-08-15 | Csl Limited | Coagulation factor binding proteins and uses thereof |
| KR20190080949A (ko) * | 2016-11-23 | 2019-07-08 | 바이오버라티브 테라퓨틱스 인크. | 응고 인자 ｉｘ 및 응고 인자 ｘ에 결합하는 이중특이적 항체 |
| JP7366747B2 (ja) | 2017-02-01 | 2023-10-23 | ノヴォ ノルディスク アー／エス | 血液凝固抗体 |
| GB201709970D0 (en) | 2017-06-22 | 2017-08-09 | Kymab Ltd | Bispecific antigen-binding molecules |
| TWI667254B (zh) | 2017-09-29 | 2019-08-01 | 日商中外製藥股份有限公司 | 具有第viii凝血因子(fviii)輔因子機能替代活性的多重特異性抗原結合分子及含有此分子作為有效成分之藥學製劑 |
| WO2019088143A1 (ja) | 2017-11-01 | 2019-05-09 | 中外製薬株式会社 | 生物活性が低下した抗体バリアントおよびアイソフォーム |
| US11220554B2 (en) | 2018-09-07 | 2022-01-11 | Novo Nordisk A/S | Procoagulant antibodies |
| JP6761142B1 (ja) | 2018-08-01 | 2020-09-23 | ノヴォ ノルディスク アー／エス | 改良された血液凝固促進抗体 |
| LT3723858T (lt) | 2018-12-21 | 2022-02-10 | Kymab Limited | Fixaxfx bispecifiniai antikūnai, turintys bendrą lenvąją grandinę |
| EP4097141A1 (en) | 2020-01-30 | 2022-12-07 | Novo Nordisk A/S | Bispecific factor viii mimetic antibodies |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT368883B (de) | 1980-07-22 | 1982-11-25 | Immuno Ag | Verfahren zur herstellung einer neuen blutgerinnungsfoerdernden praeparation auf basis von humanproteinen |
| US4873316A (en) | 1987-06-23 | 1989-10-10 | Biogen, Inc. | Isolation of exogenous recombinant proteins from the milk of transgenic mammals |
| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| WO1994005692A1 (en) | 1992-08-27 | 1994-03-17 | Stichting Centraal Laboratorium Van De Bloedtransfusiedienst Van Het Nederlandse Rode Kruis | Antibodies specific for a haemostatic protein, their use for isolating intact protein, haemostatic compositions devoid of proteolytic cleavage products of the protein |
| DK128093D0 (da) | 1993-11-12 | 1993-11-12 | Novo Nordisk As | Hidtil ukendte forbindelser |
| MA24512A1 (fr) | 1996-01-17 | 1998-12-31 | Univ Vermont And State Agrienl | Procede pour la preparation d'agents anticoagulants utiles dans le traitement de la thrombose |
| US6013256A (en) * | 1996-09-24 | 2000-01-11 | Protein Design Labs, Inc. | Method of preventing acute rejection following solid organ transplantation |
| JP2002510321A (ja) | 1997-07-03 | 2002-04-02 | スミスクライン・ビーチャム・コーポレイション | 抗−第ＩＸ因子 Ｆａｂフラグメントの結晶構造およびペプチド模倣物デザインのための使用方法 |
| AT411997B (de) * | 1999-09-14 | 2004-08-26 | Baxter Ag | Faktor ix/faktor ixa aktivierende antikörper und antikörper-derivate |
| CU23007A1 (es) * | 2001-04-06 | 2004-12-17 | Ct De Inmunologia Molecular Ct De Inmunologia Mole | Combinaciones inmunoterapéuticas para el tratamiencombinaciones inmunoterapéuticas para el tratamiento de tumores que sobre-expresan gangliósidos to de tumores que sobre-expresan gangliósidos |
| US6969517B2 (en) * | 2001-05-03 | 2005-11-29 | Emd Lexigen Research Center Corp. | Recombinant tumor specific antibody and use thereof |
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- 2004-09-07 DE DE602004018788T patent/DE602004018788D1/de not_active Expired - Lifetime
- 2004-09-07 CA CA002538895A patent/CA2538895A1/en not_active Abandoned
- 2004-09-07 ES ES04764918T patent/ES2320665T3/es not_active Expired - Lifetime
- 2004-09-07 JP JP2006525744A patent/JP4887148B2/ja not_active Expired - Fee Related
- 2004-09-07 EP EP04764918A patent/EP1660536B1/en not_active Expired - Lifetime
- 2004-09-07 AU AU2004271706A patent/AU2004271706B2/en not_active Expired
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| DE602004018788D1 (de) | 2009-02-12 |
| WO2005025615A3 (en) | 2005-06-02 |
| WO2005025615A2 (en) | 2005-03-24 |
| JP2007504812A (ja) | 2007-03-08 |
| AU2004271706A1 (en) | 2005-03-24 |
| ATE419277T1 (de) | 2009-01-15 |
| AU2004271706B2 (en) | 2010-09-02 |
| JP4887148B2 (ja) | 2012-02-29 |
| EP1660536A2 (en) | 2006-05-31 |
| EP1660536B1 (en) | 2008-12-31 |
| US20050058640A1 (en) | 2005-03-17 |
| ES2320665T3 (es) | 2009-05-27 |
| US7297336B2 (en) | 2007-11-20 |
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