ES2391613T3 - Un procedimiento para purificar el factor de coagulación VIII - Google Patents
Un procedimiento para purificar el factor de coagulación VIII Download PDFInfo
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- ES2391613T3 ES2391613T3 ES09769279T ES09769279T ES2391613T3 ES 2391613 T3 ES2391613 T3 ES 2391613T3 ES 09769279 T ES09769279 T ES 09769279T ES 09769279 T ES09769279 T ES 09769279T ES 2391613 T3 ES2391613 T3 ES 2391613T3
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/745—Blood coagulation or fibrinolysis factors
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/745—Blood coagulation or fibrinolysis factors
- C07K14/755—Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
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Landscapes
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- Chemical & Material Sciences (AREA)
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| EP08158893 | 2008-06-24 | ||
| PCT/EP2009/057883 WO2009156430A1 (en) | 2008-06-24 | 2009-06-24 | A process of purifying coagulation factor viii |
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| ES12179389.7T Active ES2538706T3 (es) | 2008-06-24 | 2009-06-24 | Procedimiento de purificación del factor de coagulación VIII |
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| EP2167526B1 (en) | 2007-07-11 | 2011-03-30 | Novo Nordisk A/S | Purification of factor viii using a mixed-mode or multimodal resin |
| EP2027875A1 (en) * | 2007-08-23 | 2009-02-25 | Octapharma AG | A Process for Isolation and Purification of a Target Protein free of Prion Protein (PrPSC) |
| AU2009284113B2 (en) | 2008-08-21 | 2015-05-14 | Octapharma Ag | Recombinantly produced human factor VIII and IX |
| KR101691443B1 (ko) * | 2008-09-03 | 2016-12-30 | 옥타파마 아게 | 재조합에 의해 제조된 인자 ⅷ을 위한 신규한 보호 조성물 |
| EP2326658A4 (en) * | 2008-09-12 | 2013-04-10 | Ge Healthcare Bio Sciences Ab | REMOVAL OF REINFORCED PROTEIN AGGREGATES WITH MULTIMODAL ANION DERIVATIVES IN THE PRESENCE OF TWITTERS WITHOUT PROTEINS |
| CN102858797B (zh) * | 2010-03-30 | 2016-05-11 | 奥克塔法马股份有限公司 | 纯化生长因子蛋白的方法 |
| TR201911082T4 (tr) * | 2010-03-30 | 2019-08-21 | Octapharma Ag | K vitaminine bağımlı proteinlerin saflaştırılması için bir işlem. |
| ES2639641T3 (es) | 2010-04-20 | 2017-10-27 | Octapharma Ag | Nuevo agente estabilizante para proteínas farmacéuticas |
| WO2012049285A1 (en) | 2010-10-14 | 2012-04-19 | Octapharma Ag | A method for the quantitative glycosylation analysis of proteins |
| JP5947802B2 (ja) * | 2010-11-05 | 2016-07-06 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | ミックスモードクロマトグラフィーによる抗体捕捉の最適化方法 |
| KR101980164B1 (ko) * | 2011-05-13 | 2019-05-20 | 옥타파마 아게 | 재조합 ｆｖｉｉｉ의 생산에서 진핵 세포의 생산성을 증가시키는 방법 |
| ES2613723T3 (es) | 2011-06-17 | 2017-05-25 | School Juridical Person Higashi-Nippon-Gakuen | Método de medición del tiempo de coagulación sanguínea para detectar anticoagulantes de Lupus |
| EP2771358A4 (en) * | 2011-10-26 | 2015-08-26 | Bio Rad Laboratories | ELIMINATION OF VIRAL AGENTS IN MIXED MODE CHROMATOGRAPHY |
| AU2013334644B2 (en) * | 2012-10-24 | 2018-07-12 | Genzyme Corporation | Elution of biomolecules from multi-modal resins using mes and mops as mobile phase modifiers |
| US20140154233A1 (en) * | 2012-12-05 | 2014-06-05 | Csl Limited | Method of purifying therapeutic proteins |
| US10188965B2 (en) | 2012-12-05 | 2019-01-29 | Csl Behring Gmbh | Hydrophobic charge induction chromatographic depletion of a protein from a solution |
| CN103880947B (zh) * | 2012-12-21 | 2016-01-13 | 武汉禾元生物科技股份有限公司 | 一种分离纯化高纯度重组人血清白蛋白的层析方法 |
| HK1219964A1 (zh) | 2013-03-08 | 2017-04-21 | Genzyme Corporation | 治疗性蛋白药物物质的整合连续制造 |
| US20160130361A1 (en) * | 2013-06-13 | 2016-05-12 | Biogen Ma Inc. | Anti-factor viii antibodies or uses thereof |
| CA2910770C (en) | 2013-07-12 | 2018-02-27 | Merck Patent Gmbh | Removal of fragments from a sample containing a target protein using activated carbon |
| EP3043813B1 (en) * | 2013-08-08 | 2021-01-13 | Bioverativ Therapeutics Inc. | Purification of chimeric fviii molecules |
| KR101988705B1 (ko) | 2013-09-24 | 2019-06-12 | 화이자 인코포레이티드 | 재조합 인간 응고 인자 Xa 단백질의 이질적 집단을 포함하는 조성물 |
| TWI709569B (zh) | 2014-01-17 | 2020-11-11 | 美商健臻公司 | 無菌層析樹脂及其用於製造方法的用途 |
| TWI671312B (zh) * | 2014-01-17 | 2019-09-11 | 美商健臻公司 | 無菌層析法及製法 |
| EP3097118B1 (en) * | 2014-01-20 | 2018-07-18 | Octapharma AG | A process for manufacturing factor viii having an improved ratio of fviii:c/fviii:ag |
| CA2936829C (en) * | 2014-01-24 | 2024-05-28 | Am-Pharma B.V. | Downstream processing of an alkaline phosphatase |
| KR102382402B1 (ko) | 2014-02-04 | 2022-04-01 | 바이오젠 엠에이 인코포레이티드 | 번역 후 변형을 강화시키기 위한 통류 방식 양이온 교환 크로마토그래피의 용도 |
| CN104861060A (zh) * | 2014-02-21 | 2015-08-26 | 神州细胞工程有限公司 | 一种纯化凝血因子viii的方法 |
| CN106232614A (zh) | 2014-05-29 | 2016-12-14 | 新加坡科技研究局 | 蛋白质提取方法 |
| US10626164B2 (en) * | 2014-07-25 | 2020-04-21 | Csl Limited | Purification of VWF |
| GB201506117D0 (en) | 2015-04-10 | 2015-05-27 | Ge Healthcare Bio Sciences Ab | Method for chromatography |
| GB201506113D0 (en) | 2015-04-10 | 2015-05-27 | Ge Healthcare Bio Sciences Ab | Method for chromatography |
| WO2016207328A1 (en) * | 2015-06-24 | 2016-12-29 | Glycotope Gmbh | PROCESS FOR THE PURIFICATION OF γ-CARBOXYLATED POLYPEPTIDES |
| EP3205665A1 (en) | 2016-02-11 | 2017-08-16 | Octapharma AG | Method of separating factor viii from blood products |
| GB201617240D0 (en) * | 2016-10-11 | 2016-11-23 | Profactor Pharma Ltd | Purification process |
| CN111183151B (zh) * | 2017-06-23 | 2024-06-07 | 武田药品工业株式会社 | 因子viii亚种的纯化 |
| CN107226859B (zh) * | 2017-08-10 | 2020-11-24 | 博雅生物制药集团股份有限公司 | 一种人凝血因子ⅷ的制备方法 |
| US11584777B2 (en) | 2017-08-31 | 2023-02-21 | Green Cross Corporation | Method for purifying a sulfatase protein |
| CA3080656A1 (en) | 2017-10-30 | 2019-05-09 | Baxalta GmbH | Environmentally compatible detergents for inactivation of lipid-enveloped viruses |
| AU2019332764B2 (en) | 2018-08-31 | 2025-05-29 | Genzyme Corporation | Sterile chromatography resin and use thereof in manufacturing processes |
| EP4093745A4 (en) * | 2020-01-20 | 2024-03-06 | Wuxi Biologics Ireland Limited | NEW WASH BUFFER SOLUTION FOR AFFINITY CHROMATOGRAPHY |
| CN118217951B (zh) * | 2024-04-01 | 2025-05-23 | 山东建筑大学 | 一种水中的高纯度磷回收装置和方法 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4540573A (en) | 1983-07-14 | 1985-09-10 | New York Blood Center, Inc. | Undenatured virus-free biologically active protein derivatives |
| US5605884A (en) * | 1987-10-29 | 1997-02-25 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Factor VIII formulations in high ionic strength media |
| US5316680A (en) * | 1992-10-21 | 1994-05-31 | Cornell Research Foundation, Inc. | Multimodal chromatographic separation media and process for using same |
| JPH08506710A (ja) | 1993-06-11 | 1996-07-16 | ノーザン・テレコム・リミテッド | ユーザ制御呼管理サービス方法および装置 |
| DE4337573C1 (de) * | 1993-11-04 | 1995-05-18 | Octapharma Ag | Verfahren zur Herstellung einer virusinaktivierten Faktor VIII enthaltenden Fraktion mittels chromatographischer Methoden |
| SE9403915D0 (sv) | 1994-11-14 | 1994-11-14 | Annelie Almstedt | Process A |
| AUPR638801A0 (en) * | 2001-07-13 | 2001-08-09 | Life Therapeutics Limited | Factor viii separation |
| WO2005082483A1 (en) * | 2004-02-27 | 2005-09-09 | Ge Healthcare Bio-Sciences Ab | A process for the purification of antibodies |
| PL1765866T3 (pl) * | 2004-06-07 | 2014-06-30 | Therapure Biopharma Inc | Wydzielanie białek osocza lub surowicy |
| EP1707634A1 (en) * | 2005-03-29 | 2006-10-04 | Octapharma AG | Method for isolation of recombinantly produced proteins |
| FR2887883B1 (fr) * | 2005-06-29 | 2007-08-31 | Lab Francais Du Fractionnement | Procede de separation des proteines fibrinogene, facteur xiii et colle biologique d'une fraction plasmatique solubilisee et de preparation de concentres lyophilises desdites proteines |
| EP1739179A1 (en) | 2005-06-30 | 2007-01-03 | Octapharma AG | Serum-free stable transfection and production of recombinant human proteins in human cell lines |
| WO2008008975A2 (en) * | 2006-07-14 | 2008-01-17 | Genentech, Inc. | Refolding of recombinant proteins |
| RU2324495C1 (ru) * | 2006-08-31 | 2008-05-20 | Федеральное государственное унитарное предприятие "Научно-производственное объединение по медицинским иммунобиологическим препаратам "Микроген" Министерства здравоохранения Российской Федерации | Способ получения препарата фактора свертывания viii крови человека |
| CA2674881A1 (en) * | 2007-02-01 | 2008-08-07 | Baxter International Inc. | Fviii-independent fix-mutant proteins for hemophilia a treatment |
| JP2010529155A (ja) * | 2007-06-13 | 2010-08-26 | ツェー・エス・エル・ベーリング・ゲー・エム・ベー・ハー | 出血性疾患の治療及び予防的処置における血管外投与のためのｖｗｆ安定化ｆｖｉｉｉ製剤及びｆｖｉｉｉなしのｖｗｆ製剤の使用 |
| EP2167526B1 (en) * | 2007-07-11 | 2011-03-30 | Novo Nordisk A/S | Purification of factor viii using a mixed-mode or multimodal resin |
| GB0723712D0 (en) * | 2007-12-04 | 2008-01-16 | Apitope Technology Bristol Ltd | Peptides |
| DE102008032361A1 (de) * | 2008-07-10 | 2010-01-21 | Csl Behring Gmbh | Der Einsatz von Faktor VIII und vWF bzw. vWF-enthaltenden Konzentraten zur Therapie der durch Thrombocyten-Inhibitoren induzierte Koagulopathie |
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