ES2860450T3 - Tratamiento de una enfermedad de la coagulación mediante la administración de VWF recombinante - Google Patents
Tratamiento de una enfermedad de la coagulación mediante la administración de VWF recombinante Download PDFInfo
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| CN102776260B (zh) * | 2012-07-26 | 2015-04-29 | 上海泰龙生物医药科技有限公司 | 一种高效表达重组人凝血八因子的方法 |
| ES2657291T3 (es) * | 2013-04-22 | 2018-03-02 | Csl Ltd. | Un complejo covalente de factor de von Willebrand y factor VIII asociado por un puente disulfuro |
| NL2013007B1 (en) | 2014-06-16 | 2016-07-05 | Ablynx Nv | Methods of treating TTP with immunoglobulin single variable domains and uses thereof. |
| FR3034669B1 (fr) * | 2015-04-07 | 2020-02-14 | Laboratoire Francais Du Fractionnement Et Des Biotechnologies | Nouvelle utilisation du facteur von willebrand |
| CN109804432B (zh) | 2016-04-15 | 2023-07-14 | 武田药品工业株式会社 | 提供药代动力学药物给药方案的方法和设备 |
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| CN111436193A (zh) | 2017-07-07 | 2020-07-21 | 百深公司 | 通过施用重组vwf来治疗患有严重冯维勒布兰德病的患者中的胃肠道出血 |
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| AU2019240135B2 (en) * | 2018-03-21 | 2024-10-03 | Takeda Pharmaceutical Company Limited | Separation of VWF and VWF propeptide by chromatographic methods |
| EP3917557A1 (en) * | 2019-02-01 | 2021-12-08 | Takeda Pharmaceutical Company Limited | Methods of prophylactic treatment using recombinant vwf (rvwf) |
| WO2021050718A1 (en) | 2019-09-11 | 2021-03-18 | Baxalta Incorporated | Methods of treatment related to complexes of von willebrand factor and complement c1q |
| KR20220150303A (ko) | 2020-02-04 | 2022-11-10 | 다케다 야쿠힌 고교 가부시키가이샤 | 재조합 vwf의 투여에 의한 중증 폰 빌레브란트병 환자의 월경과다 치료 |
| AU2021387981A1 (en) * | 2020-11-24 | 2023-07-06 | Band Therapeutics, Llc | Compositions and methods for treatment of bleeding disorders |
| WO2024124136A1 (en) * | 2022-12-09 | 2024-06-13 | Vega Therapeutics, Inc. | Von willebrand disease animal models |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| JPS6023084B2 (ja) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
| US4640835A (en) | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
| US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
| US4638028A (en) | 1985-04-08 | 1987-01-20 | Goodyear Tire & Rubber Company | Rubber polymerases and methods for their production and use |
| AU591671B2 (en) | 1985-04-11 | 1989-12-14 | Children's Medical Center Corporation | Von willebrand factor |
| EP0206448B1 (en) | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
| US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| SE504074C2 (sv) * | 1993-07-05 | 1996-11-04 | Pharmacia Ab | Proteinberedning för subkutan, intramuskulär eller intradermal administrering |
| DE4435485C1 (de) * | 1994-10-04 | 1996-03-21 | Immuno Ag | Verfahren zur Gewinnung von hochreinem von Willebrand-Faktor |
| AT403764B (de) * | 1996-03-15 | 1998-05-25 | Immuno Ag | Stabiler faktor viii/vwf-komplex |
| AT405403B (de) * | 1997-02-27 | 1999-08-25 | Immuno Ag | Reinigung von von willebrand-faktor durch kationenaustauscherchromatographie |
| AT406373B (de) * | 1997-02-27 | 2000-04-25 | Immuno Ag | Verfahren zur reinigung von faktor viii/vwf-komplex mittels kationenaustauscherchromatographie |
| US6531577B1 (en) | 1997-12-15 | 2003-03-11 | Hemasure Denmark A/S | von Willebrand factor (vWF)-containing preparation, process for preparing vWF-containing preparations, and use of such preparations |
| US6864403B1 (en) | 1998-10-15 | 2005-03-08 | E. I. Du Pont De Nemours And Company | Plant protein disulfide isomerases |
| US20040014657A1 (en) * | 2001-11-05 | 2004-01-22 | Jan Ohrstrom | Use of blood coagulation factor XIII for treating haemophilia A |
| WO2005012354A1 (en) * | 2003-07-31 | 2005-02-10 | Zlb Behring Gmbh | Method for extending the half-life of fviii |
| EP1593388A1 (en) | 2004-05-05 | 2005-11-09 | ZLB Behring GmbH | Therapeutic plasma protein-concentrates containing von willebrand factor as high molecular weight multimers |
| US20060094104A1 (en) | 2004-10-29 | 2006-05-04 | Leopold Grillberger | Animal protein-free media for cultivation of cells |
| CA2591852A1 (en) * | 2004-12-27 | 2006-07-06 | Baxter International Inc. | Polymer-von willebrand factor-conjugates |
| EP3653699A1 (en) | 2006-01-04 | 2020-05-20 | Baxalta Incorporated | Oligopeptide-free cell culture media |
| CA2690218C (en) * | 2007-06-13 | 2017-02-28 | Csl Behring Gmbh | Use of vwf stabilized fviii preparations and of vwf preparations without fviii for extravascular administration in the therapy and prophylactic treatment of bleeding disorders |
| KR20100095441A (ko) | 2007-11-09 | 2010-08-30 | 백스터 인터내셔널 인코포레이티드 | 변형된 재조합 인자 ⅷ 및 폰 빌레브란트 인자 및 사용 방법 |
| JP2009127455A (ja) | 2007-11-20 | 2009-06-11 | Bando Kiko Co Ltd | 往復動エンジン |
| SG187410A1 (en) | 2007-12-28 | 2013-02-28 | Baxter Int | Recombinant vwf formulations |
| ES2298096B1 (es) * | 2008-01-08 | 2009-01-01 | Grifols, S.A. | Procedimiento para la obtencion de un concentrado de factor von willebrand o del complejo de factor viii/factor von willebrand y utilizacionde los mismos. |
| AU2009262476C1 (en) * | 2008-06-24 | 2016-06-02 | Csl Behring Gmbh | Factor VIII, von Willebrand factor or complexes thereof with prolonged in vivo half-life |
| TWI593421B (zh) * | 2008-10-21 | 2017-08-01 | 巴克斯歐塔公司 | 凍乾的重組ｖｗｆ調配物 |
| US20110072524A1 (en) * | 2009-08-04 | 2011-03-24 | Baxter International Inc. | Transgenic Mouse Lacking Endogenous FVIII and VWF - A Model of Hemophilia A |
| KR101924120B1 (ko) * | 2010-07-08 | 2018-11-30 | 박스알타 인코퍼레이티드 | 세포 배양에서 재조합 ａｄａｍｔｓ13을 생산하는 방법 |
| US20120006800A1 (en) | 2010-07-09 | 2012-01-12 | Illinois Tool Works Inc. | Weld bead feature communication systems and devices |
| RU2680402C2 (ru) * | 2011-06-10 | 2019-02-21 | Бакстер Интернэшнл Инк. | Лечение нарушений свертываемости крови путем введения рекомбинантного фв |
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