JP2012506387A5 - - Google Patents
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- JP2012506387A5 JP2012506387A5 JP2011532347A JP2011532347A JP2012506387A5 JP 2012506387 A5 JP2012506387 A5 JP 2012506387A5 JP 2011532347 A JP2011532347 A JP 2011532347A JP 2011532347 A JP2011532347 A JP 2011532347A JP 2012506387 A5 JP2012506387 A5 JP 2012506387A5
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- Prior art keywords
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- amino acid
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- Prior art date
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- 238000009472 formulation Methods 0.000 claims description 116
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| KR102698051B1 (ko) * | 2015-02-27 | 2024-08-26 | 더 보드 오브 리젠츠 오브 더 유니버시티 오브 텍사스 시스템 | 폴리펩타이드 치료제 및 이의 용도 |
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| MX2020009788A (es) | 2018-03-21 | 2020-12-09 | Takeda Pharmaceuticals Co | Separación de factor de von willebrand (vwf) y propéptido de factor de von willebrand (vwf) por métodos cromatográficos. |
| AU2019339260B2 (en) | 2018-09-10 | 2025-06-26 | Rein Therapeutics, Inc. | Modified peptide fragments of Cav-1 protein and the use thereof in the treatment of fibrosis |
| KR20210134642A (ko) | 2019-02-01 | 2021-11-10 | 다케다 야쿠힌 고교 가부시키가이샤 | 재조합 vwf (rvwf)를 이용한 예방 치료 방법 |
| US20220401524A1 (en) | 2019-09-11 | 2022-12-22 | Takeda Pharmaceutical Company Limited | Methods of treatment related to complexes of von willebrand factor and complement c1q |
| AR121268A1 (es) | 2020-02-04 | 2022-05-04 | Takeda Pharmaceuticals Co | Tratamiento de la menorragia en pacientes con enfermedad de von willebrand grave mediante la administración de vwf recombinante |
| CN111789867B (zh) * | 2020-08-27 | 2022-01-11 | 中国人民解放军军事科学院军事医学研究院 | 一种适用于提高血浆干粉功能的适配液 |
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Family Cites Families (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3941763A (en) | 1975-03-28 | 1976-03-02 | American Home Products Corporation | PGlu-D-Met-Trp-Ser-Tyr-D-Ala-Leu-Arg-Pro-Gly-NH2 and intermediates |
| US8597910B1 (en) | 1985-04-11 | 2013-12-03 | Children's Medical Center Corporation | DNA encoding Von Willebrand Factor (VWF) and methods and cells for producing VFW, and VFW produced by the DNA, methods and cells |
| WO1986006096A1 (en) | 1985-04-11 | 1986-10-23 | The Children's Medical Center Corporation | Von willebrand factor |
| US5900476A (en) * | 1986-05-30 | 1999-05-04 | The Scripps Research Institute | Therapeutic domains of van Willebrand factor |
| US5201033A (en) | 1990-01-17 | 1993-04-06 | International Business Machines Corporation | Method for controlling cursor movements on certain computer workstations |
| ATE283864T1 (de) * | 1991-06-20 | 2004-12-15 | Aventis Behring L L C | Ein verfahren zur herstellung therapeutisch wirksamer bruchstücke von von willebrand-faktor |
| US5847086A (en) * | 1991-06-20 | 1998-12-08 | Centeon L.L.C. | Therapeutic fragments of von Willebrand factor |
| US5670132A (en) * | 1994-09-20 | 1997-09-23 | Immunomedics, Inc. | Modified radioantibody fragments for reduced renal uptake |
| DE4435485C1 (de) | 1994-10-04 | 1996-03-21 | Immuno Ag | Verfahren zur Gewinnung von hochreinem von Willebrand-Faktor |
| DE4435392B4 (de) * | 1994-10-04 | 2008-02-07 | Immuno Ag | Verfahren zur Trennung von vWF in hochmolekularen vWF und niedermolekularen vWF |
| US20010046487A1 (en) | 1994-12-30 | 2001-11-29 | Roser Bruce J. | Methods for loading platelets, stabilizing platelets for dry storage and compositions obtained thereby |
| US7244824B2 (en) * | 1995-01-19 | 2007-07-17 | Quadrant Drug Delivery Limited | Dried blood factor composition comprising trehalose |
| US7253262B2 (en) * | 1995-01-19 | 2007-08-07 | Quandrant Drug Delivery Limited | Dried blood factor composition comprising trehalose |
| GB9501040D0 (en) | 1995-01-19 | 1995-03-08 | Quadrant Holdings Cambridge | Dried composition |
| US6267958B1 (en) * | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
| MX9800684A (es) | 1995-07-27 | 1998-04-30 | Genentech Inc | Formulacion de proteinas liofilizadas isotonicas estables. |
| US6005077A (en) * | 1995-11-10 | 1999-12-21 | Immuno Aktiengesellschaft | Use of von willebrand factor and pharmaceutical formulation |
| US5925738A (en) * | 1995-12-01 | 1999-07-20 | The American National Red Cross | Methods of production and use of liquid formulations of plasma proteins |
| AT403764B (de) * | 1996-03-15 | 1998-05-25 | Immuno Ag | Stabiler faktor viii/vwf-komplex |
| WO1998003683A1 (en) * | 1996-07-19 | 1998-01-29 | The Regents Of The University Of Michigan | Dna encoding canine von willebrand factor and methods of use |
| SE9604296D0 (sv) | 1996-11-22 | 1996-11-22 | Astra Ab | New pharmaceutical formulation of polypeptides |
| AT405740B (de) * | 1996-12-13 | 1999-11-25 | Immuno Ag | Von willebrand-faktor-derivat sowie ein verfahren zur isolierung von proteinen |
| US20020019036A1 (en) | 1996-12-13 | 2002-02-14 | Hans-Peter Schwarz | Von willebrand factor derivatives and methods of isolating proteins that bind to von willebrand factor |
| 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 |
| AT405485B (de) | 1997-05-28 | 1999-08-25 | Immuno Ag | Eine das vwf-propeptid enthaltende pharmazeutische präparation |
| US6005007A (en) * | 1997-07-18 | 1999-12-21 | Farmer; Luc J. | Retinoids, methods for their production and use |
| US6310183B1 (en) * | 1997-09-10 | 2001-10-30 | Novo Nordisk A/S | Coagulation factor VIIa composition |
| 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 |
| EP1148063A1 (de) | 2000-04-18 | 2001-10-24 | Octapharma AG | Haemostatisch aktives vWF enthaltendes Präparat und Verfahren zu seiner Herstellung |
| US20040038878A1 (en) * | 2000-08-04 | 2004-02-26 | Masahiko Tanikawa | Injectable protein formulations |
| WO2002013860A1 (en) | 2000-08-11 | 2002-02-21 | Chugai Seiyaku Kabushiki Kaisha | Stabilized antibody-containing preparations |
| DE10043124A1 (de) * | 2000-08-31 | 2002-03-14 | Max Delbrueck Centrum | Verfahren zur Diagnostik von neuronalen Erkrankungen sowie zur Behandlung der defizienten primären Hämostase |
| AU2001291653A1 (en) | 2000-10-02 | 2002-04-15 | Novo-Nordisk A/S | Industrial-scale serum-free production of recombinant factor vii in mammalian cells |
| IL155002A0 (en) * | 2000-10-12 | 2003-10-31 | Genentech Inc | Reduced-viscosity concentrated protein formulations |
| CN1671420A (zh) | 2002-06-21 | 2005-09-21 | 诺和诺德医疗保健公司 | Peg化因子ⅶ糖型 |
| AU2003291689A1 (en) | 2002-10-31 | 2004-05-25 | Protein Design Labs, Inc. | Stable liquid pharmaceutical formulation of antibodies that are prone to isomerization |
| ES2229931B1 (es) * | 2003-10-03 | 2006-01-16 | Grifols, S.A. | Composicion liquida bilogicamente estable de fviii, de fvw o del complejo fviii/fvw humanos. |
| FR2861395B1 (fr) | 2003-10-23 | 2006-02-17 | Lab Francais Du Fractionnement | Facteur viii viralement securise a faible teneur en multimeres superieurs |
| EP2298287B1 (en) * | 2003-12-19 | 2018-04-11 | Novo Nordisk Health Care AG | Stabilised compositions of factor VII polypeptides |
| US20060008415A1 (en) * | 2004-06-25 | 2006-01-12 | Protein Design Labs, Inc. | Stable liquid and lyophilized formulation of proteins |
| FR2874216B1 (fr) | 2004-08-16 | 2006-11-03 | Lab Francais Du Fractionnement | Procede de preparation d'un concentre de facteur von willebrand (fvw) par voie chromatographique et concentre de fvw susceptible d'etre ainsi obtenu |
| DE102004044421B4 (de) * | 2004-09-14 | 2010-06-24 | Biotest Ag | Verfahren zur Trennung eines von Willebrand Faktors mit einer spezifischen VWF-Aktivität von wenigstens 50 E/mg VWF-Antigen von einem von Willebrand Faktor mit niedriger Aktivität und Verwendung von Hydroxylapatit dafür |
| KR20070092754A (ko) * | 2004-12-27 | 2007-09-13 | 백스터 인터내셔널 인코포레이티드 | 중합체 - 폰 빌레브란트 인자 - 접합체 |
| EP1707634A1 (en) * | 2005-03-29 | 2006-10-04 | Octapharma AG | Method for isolation of recombinantly produced proteins |
| GB0509443D0 (en) * | 2005-05-09 | 2005-06-15 | Prometic Biosciences Ltd | Affinity adsorbents for factor VIII and von willebrand's factor |
| EP2264162A1 (en) * | 2005-07-02 | 2010-12-22 | Arecor Limited | Stable aqueous systems comprising proteins |
| AU2006272804B2 (en) * | 2005-07-22 | 2011-02-24 | Amgen Inc. | Concentrated protein lyophilates, methods, and uses |
| JP5364382B2 (ja) * | 2006-02-07 | 2013-12-11 | シャイアー ヒューマン ジェネティック セラピーズ インコーポレイテッド | 遊離チオール部分を有するタンパク質の安定化された組成物 |
| GB0700523D0 (en) * | 2007-01-11 | 2007-02-21 | Insense Ltd | The Stabilisation Of Proteins |
| US7559509B1 (en) | 2007-02-12 | 2009-07-14 | Thomas C. Taylor | Large cryogenic tank logistics for in-space vehicles |
| US20100137211A1 (en) * | 2007-04-11 | 2010-06-03 | Monahan Paul E | Methods and compositions for intra-articular coagulation proteins |
| WO2008134310A1 (en) * | 2007-04-26 | 2008-11-06 | Bayer Healthcare Llc | Stabilization of liquid solutions of recombinant protein for frozen storage |
| 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 |
| FR2920429B1 (fr) * | 2007-08-30 | 2012-10-05 | Lfb Biotechnologies | Procede de purification du facteur viii et du facteur von willebrand |
| NZ586383A (en) * | 2007-12-28 | 2012-11-30 | 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. |
| 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 |
| US20100092566A1 (en) * | 2008-10-15 | 2010-04-15 | Alessi Thomas R | Highly concentrated drug particles, formulations, suspensions and uses thereof |
| TWI670072B (zh) * | 2008-10-21 | 2019-09-01 | 美商巴克斯歐塔公司 | 凍乾的重組ｖｗｆ調配物 |
| KR20110093775A (ko) * | 2008-11-03 | 2011-08-18 | 바이엘 헬스케어 엘엘씨 | 혈우병 치료 방법 |
| NZ594698A (en) * | 2009-02-05 | 2013-08-30 | Pierre Philippart | Method and means for producing tissues and tissues obtained |
| SG10201408106WA (en) * | 2009-08-20 | 2015-01-29 | Baxter Int | Purification of vwf for increased removal of non-lipid enveloped viruses |
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