ES2772933T3 - Factor de von Willebrand modificado que tiene una semivida mejorada - Google Patents
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- ES2772933T3 ES2772933T3 ES16712738T ES16712738T ES2772933T3 ES 2772933 T3 ES2772933 T3 ES 2772933T3 ES 16712738 T ES16712738 T ES 16712738T ES 16712738 T ES16712738 T ES 16712738T ES 2772933 T3 ES2772933 T3 ES 2772933T3
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- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
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- 238000004904 shortening Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- KYOYLUVYCHVYGC-BUOKYLHBSA-M sodium (E)-but-2-enedioic acid (E)-4-hydroxy-4-oxobut-2-enoate Chemical compound [Na+].OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C([O-])=O KYOYLUVYCHVYGC-BUOKYLHBSA-M 0.000 description 1
- BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical compound [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000000176 sodium gluconate Substances 0.000 description 1
- 229940005574 sodium gluconate Drugs 0.000 description 1
- 239000001433 sodium tartrate Substances 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
- GNBVPFITFYNRCN-UHFFFAOYSA-M sodium thioglycolate Chemical compound [Na+].[O-]C(=O)CS GNBVPFITFYNRCN-UHFFFAOYSA-M 0.000 description 1
- 229940046307 sodium thioglycolate Drugs 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- LLVQEXSQFBTIRD-UHFFFAOYSA-M sodium;2,3,4-trihydroxy-4-oxobutanoate;hydrate Chemical compound O.[Na+].OC(=O)C(O)C(O)C([O-])=O LLVQEXSQFBTIRD-UHFFFAOYSA-M 0.000 description 1
- KMPHTYSTEHXSTL-UHFFFAOYSA-M sodium;2-hydroxypropanoate;2-hydroxypropanoic acid Chemical compound [Na+].CC(O)C(O)=O.CC(O)C([O-])=O KMPHTYSTEHXSTL-UHFFFAOYSA-M 0.000 description 1
- VDZDAHYKYRVHJR-UHFFFAOYSA-M sodium;2-hydroxypropanoate;hydrate Chemical compound [OH-].[Na+].CC(O)C(O)=O VDZDAHYKYRVHJR-UHFFFAOYSA-M 0.000 description 1
- OESFSXYRSCBAQJ-UHFFFAOYSA-M sodium;3-carboxy-3,5-dihydroxy-5-oxopentanoate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.OC(=O)CC(O)(C(O)=O)CC([O-])=O OESFSXYRSCBAQJ-UHFFFAOYSA-M 0.000 description 1
- VBGUQBPWJMPQBI-UHFFFAOYSA-M sodium;butanedioic acid;4-hydroxy-4-oxobutanoate Chemical compound [Na+].OC(=O)CCC(O)=O.OC(=O)CCC([O-])=O VBGUQBPWJMPQBI-UHFFFAOYSA-M 0.000 description 1
- JISIBLCXFLGVJX-UHFFFAOYSA-M sodium;butanedioic acid;hydroxide Chemical compound [OH-].[Na+].OC(=O)CCC(O)=O JISIBLCXFLGVJX-UHFFFAOYSA-M 0.000 description 1
- KIJIBEBWNNLSKE-UHFFFAOYSA-M sodium;oxalic acid;hydroxide Chemical compound [OH-].[Na+].OC(=O)C(O)=O KIJIBEBWNNLSKE-UHFFFAOYSA-M 0.000 description 1
- UQZIYBXSHAGNOE-XNSRJBNMSA-N stachyose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)O2)O)O1 UQZIYBXSHAGNOE-XNSRJBNMSA-N 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
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- SFVFIFLLYFPGHH-UHFFFAOYSA-M stearalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SFVFIFLLYFPGHH-UHFFFAOYSA-M 0.000 description 1
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- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
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- 238000011830 transgenic mouse model Methods 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 150000004043 trisaccharides Chemical class 0.000 description 1
- JYXKLAOSCQDVIX-NFMYELBMSA-K trisodium (E)-but-2-enedioate (E)-4-hydroxy-4-oxobut-2-enoate Chemical compound [Na+].[Na+].[Na+].OC(=O)\C=C\C([O-])=O.[O-]C(=O)\C=C\C([O-])=O JYXKLAOSCQDVIX-NFMYELBMSA-K 0.000 description 1
- ZHSGGJXRNHWHRS-VIDYELAYSA-N tunicamycin Chemical compound O([C@H]1[C@@H]([C@H]([C@@H](O)[C@@H](CC(O)[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C(NC(=O)C=C2)=O)O)O1)O)NC(=O)/C=C/CC(C)C)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)=O ZHSGGJXRNHWHRS-VIDYELAYSA-N 0.000 description 1
- MEYZYGMYMLNUHJ-UHFFFAOYSA-N tunicamycin Natural products CC(C)CCCCCCCCCC=CC(=O)NC1C(O)C(O)C(CC(O)C2OC(C(O)C2O)N3C=CC(=O)NC3=O)OC1OC4OC(CO)C(O)C(O)C4NC(=O)C MEYZYGMYMLNUHJ-UHFFFAOYSA-N 0.000 description 1
- 230000006107 tyrosine sulfation Effects 0.000 description 1
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- 229940046009 vitamin E Drugs 0.000 description 1
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- 208000020294 von Willebrand disease 1 Diseases 0.000 description 1
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Classifications
-
- 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)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/36—Blood coagulation or fibrinolysis factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/36—Blood coagulation or fibrinolysis factors
- A61K38/37—Factors VIII
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Toxicology (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15158065 | 2015-03-06 | ||
| PCT/EP2016/054647 WO2016142288A1 (en) | 2015-03-06 | 2016-03-04 | Modified von willebrand factor having improved half-life |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2772933T3 true ES2772933T3 (es) | 2020-07-08 |
Family
ID=52629450
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES16712738T Active ES2772933T3 (es) | 2015-03-06 | 2016-03-04 | Factor de von Willebrand modificado que tiene una semivida mejorada |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US11155601B2 (https=) |
| EP (1) | EP3265483B1 (https=) |
| JP (1) | JP2018510212A (https=) |
| KR (1) | KR20170125941A (https=) |
| CN (1) | CN107406493B (https=) |
| AU (1) | AU2016231327B2 (https=) |
| BR (1) | BR112017018468A2 (https=) |
| CA (1) | CA2978374A1 (https=) |
| DK (1) | DK3265483T3 (https=) |
| ES (1) | ES2772933T3 (https=) |
| SG (1) | SG11201706659WA (https=) |
| WO (1) | WO2016142288A1 (https=) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL319473A (en) | 2016-12-02 | 2025-05-01 | Bioverativ Therapeutics Inc | Methods for treating hemophilic arthritis using chimeric blood clotting factors |
| CA3069295A1 (en) | 2017-07-07 | 2019-01-10 | Baxalta Incorporated | Treatment of gastrointestinal bleeding in patients with severe von willebrand disease by administration of recombinant vwf |
| BR112020022164A2 (pt) | 2018-05-18 | 2021-02-02 | Bioverativ Therapeutics Inc. | métodos de tratamento de hemofilia a |
| US20220395560A1 (en) * | 2019-02-01 | 2022-12-15 | Takeda Pharmaceutical Company Limited | METHODS OF PROPHYLACTIC TREATMENT USING RECOMBINANT VWF (rVWF) |
| US12128090B2 (en) * | 2019-02-01 | 2024-10-29 | Takeda Pharmaceutical Company Limited | Methods of prophylactic treatment using recombinant VWF (rVWF) |
| CN114072420B (zh) * | 2019-07-04 | 2024-06-11 | 康诺贝林伦瑙有限公司 | 用于增加凝血因子viii的体外稳定性的截短的血管性血友病因子(vwf) |
| JP7680442B2 (ja) * | 2019-11-11 | 2025-05-20 | ツェー・エス・エル・ベーリング・レングナウ・アクチエンゲゼルシャフト | 第ｖｉｉｉ因子に対する寛容を誘導するためのポリペプチド |
Family Cites Families (84)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4444887A (en) | 1979-12-10 | 1984-04-24 | Sloan-Kettering Institute | Process for making human antibody producing B-lymphocytes |
| US4716111A (en) | 1982-08-11 | 1987-12-29 | Trustees Of Boston University | Process for producing human antibodies |
| GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
| GB8422238D0 (en) | 1984-09-03 | 1984-10-10 | Neuberger M S | Chimeric proteins |
| US4970300A (en) | 1985-02-01 | 1990-11-13 | New York University | Modified factor VIII |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| GB8720833D0 (en) | 1987-09-04 | 1987-10-14 | Celltech Ltd | Recombinant dna product |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| GB8907617D0 (en) | 1989-04-05 | 1989-05-17 | Celltech Ltd | Drug delivery system |
| US5413923A (en) | 1989-07-25 | 1995-05-09 | Cell Genesys, Inc. | Homologous recombination for universal donor cells and chimeric mammalian hosts |
| GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
| EP1690934A3 (en) | 1990-01-12 | 2008-07-30 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| ATE300615T1 (de) | 1990-08-29 | 2005-08-15 | Genpharm Int | Transgene mäuse fähig zur produktion heterologer antikörper |
| EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
| IE922437A1 (en) | 1991-07-25 | 1993-01-27 | Idec Pharma Corp | Recombinant antibodies for human therapy |
| ES2136092T3 (es) | 1991-09-23 | 1999-11-16 | Medical Res Council | Procedimientos para la produccion de anticuerpos humanizados. |
| ES2341666T3 (es) | 1991-12-02 | 2010-06-24 | Medimmune Limited | Produccion de autoanticuerpos de repertorios de segmentos de anticue rpos expresados en la superficie de fagos. |
| NZ249786A (en) | 1992-04-10 | 1995-05-26 | Sprintpak Pty Ltd | Postage stamp - luminescent coating comprises coated regions and non-coated regions |
| US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
| AU6029594A (en) | 1993-01-15 | 1994-08-15 | Enzon, Inc. | Factor viii - polymeric conjugates |
| CA2219361C (en) | 1995-04-27 | 2012-02-28 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| EP0823941A4 (en) | 1995-04-28 | 2001-09-19 | Abgenix Inc | HUMAN ANTIBODIES DERIVED FROM IMMUNIZED XENO MOUSES |
| WO1997003193A1 (en) | 1995-07-11 | 1997-01-30 | Chiron Corporation | Novel factor viii:c polypeptide analogs with altered metal-binding properties |
| SE9503380D0 (sv) | 1995-09-29 | 1995-09-29 | Pharmacia Ab | Protein derivatives |
| US20040092442A1 (en) | 1996-04-24 | 2004-05-13 | University Of Michigan | Inactivation resistant factor VIII |
| PT1754718E (pt) | 1996-04-24 | 2011-07-13 | Univ Michigan | Factor viii resistente à inactivação |
| US5916771A (en) | 1996-10-11 | 1999-06-29 | Abgenix, Inc. | Production of a multimeric protein by cell fusion method |
| EP1500329B1 (en) | 1996-12-03 | 2012-03-21 | Amgen Fremont Inc. | Human antibodies that specifically bind human TNF alpha |
| GB9625640D0 (en) | 1996-12-10 | 1997-01-29 | Celltech Therapeutics Ltd | Biological products |
| BRPI9809391B8 (pt) | 1997-04-14 | 2021-05-25 | Amgen Res Munich Gmbh | processo para a produção de um receptor de antígeno anti-humano, anticorpo humano e composição farmacêutica |
| US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
| JP4545928B2 (ja) | 1998-04-27 | 2010-09-15 | ジリップ・ファーマ・ビー．ブイ． | 第ｖｉｉｉ因子及び中性リポソームを含有する薬学的組成物 |
| AU1728800A (en) | 1998-11-18 | 2000-06-05 | Genentech Inc. | Antibody variants with higher binding affinity compared to parent antibodies |
| US7615622B2 (en) | 2001-01-12 | 2009-11-10 | University Of Maryland, Baltimore | Methods and compositions for reducing heparan sulfate proteoglycan-mediated clearance of factor VIII |
| US7205278B2 (en) | 2001-06-14 | 2007-04-17 | The Scripps Research Institute | Stabilized proteins with engineered disulfide bonds |
| EP2042196B1 (en) | 2001-10-10 | 2016-07-13 | ratiopharm GmbH | Remodelling and glycoconjugation of Granulocyte Colony Stimulating Factor (G-CSF) |
| DE60332011D1 (de) | 2002-04-29 | 2010-05-20 | Sanquin Bloedvoorziening | Antagonisten der interaktion zwischen faktor viii und lrp ("low-density lipoprotein receptor related protein") |
| US7365168B2 (en) | 2002-10-15 | 2008-04-29 | Pdl Biopharma, Inc. | Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis |
| US7217797B2 (en) | 2002-10-15 | 2007-05-15 | Pdl Biopharma, Inc. | Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis |
| US7361740B2 (en) | 2002-10-15 | 2008-04-22 | Pdl Biopharma, Inc. | Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis |
| US7041635B2 (en) | 2003-01-28 | 2006-05-09 | In2Gen Co., Ltd. | Factor VIII polypeptide |
| WO2004075923A2 (en) | 2003-02-26 | 2004-09-10 | Nektar Therapeutics Al, Corporation | Polymer-factor viii moiety conjugates |
| PT1624891E (pt) | 2003-05-06 | 2010-01-05 | Syntonix Pharmaceuticals Inc | Proteínas quiméricas de factor de coagulação-fc destinadas ao tratamento da hemofilia |
| JP2007531707A (ja) | 2003-10-15 | 2007-11-08 | ピーディーエル バイオファーマ， インコーポレイテッド | ＩＧの重鎖定常領域の位置２５０、３１４および／または４２８の変異誘発によるＦｃ融合タンパク質血清半減期の改変 |
| WO2005123780A2 (en) | 2004-04-09 | 2005-12-29 | Protein Design Labs, Inc. | Alteration of fcrn binding affinities or serum half-lives of antibodies by mutagenesis |
| GB0412181D0 (en) | 2004-06-01 | 2004-06-30 | Celltech R&D Ltd | Biological products |
| KR101468345B1 (ko) | 2004-11-12 | 2014-12-03 | 바이엘 헬스케어 엘엘씨 | Ｆｖｉｉｉ의 부위 지향 변형 |
| CA2591852A1 (en) | 2004-12-27 | 2006-07-06 | Baxter International Inc. | Polymer-von willebrand factor-conjugates |
| CA2604299A1 (en) | 2005-04-14 | 2006-10-19 | Csl Behring Gmbh | Modified coagulation factor viii with enhanced stability and its derivates |
| US7982010B2 (en) | 2006-03-31 | 2011-07-19 | Baxter International Inc. | Factor VIII polymer conjugates |
| US7645860B2 (en) | 2006-03-31 | 2010-01-12 | Baxter Healthcare S.A. | Factor VIII polymer conjugates |
| CA2647314A1 (en) | 2006-03-31 | 2007-11-08 | Baxter International Inc. | Pegylated factor viii |
| US7985839B2 (en) | 2006-03-31 | 2011-07-26 | Baxter International Inc. | Factor VIII polymer conjugates |
| AU2007338298B2 (en) | 2006-12-22 | 2013-02-07 | Csl Behring Gmbh | Modified coagulation factors with prolonged in vivo half-life |
| MX2009007145A (es) | 2006-12-27 | 2009-08-27 | Nektar Therapeutics Al Corp | Conjugados de polimero con factor viii y factor de von willebrand que tienen una ligadura liberable. |
| EP1988101A1 (en) | 2007-05-04 | 2008-11-05 | Novo Nordisk A/S | Improvement of factor VIII polypeptide titers in cell cultures |
| ES2392569T3 (es) * | 2007-06-13 | 2012-12-11 | Csl Behring Gmbh | Uso de preparaciones FVIII estabilizadas VWF para administración extravascular en la terapia y el tratamiento profiláctico de trastornos de hemorragias |
| US8399620B2 (en) | 2007-07-11 | 2013-03-19 | Novo Nordisk A/S | Purification of factor VIII using a mixed-mode or multimodal resin |
| CA2704234A1 (en) | 2007-11-09 | 2009-05-14 | Baxter International Inc. | Modified recombinant factor viii and von willebrand factor and methods of use |
| KR101582841B1 (ko) | 2008-02-27 | 2016-01-11 | 노보 노르디스크 에이/에스 | 콘쥬게이트된 인자 ｖｉｉｉ 분자 |
| KR101648734B1 (ko) | 2008-06-24 | 2016-08-18 | 체에스엘 베링 게엠베하 | 연장된 생체내 반감기를 갖는 인자 ｖｉｉｉ, 폰 빌레브란트 인자 또는 이들의 복합체 |
| KR101929641B1 (ko) | 2008-10-17 | 2018-12-14 | 박스알타 인코퍼레이티드 | 낮은 수준의 수용성 중합체를 포함하는 개질된 혈액 인자 |
| EP2398822B1 (en) | 2009-02-19 | 2013-01-02 | Novo Nordisk A/S | Modification of factor viii |
| JP5770161B2 (ja) | 2009-04-06 | 2015-08-26 | ノヴォ ノルディスク アー／エス | 血小板への第ｖｉｉｉ因子タンパク質の標的送達 |
| KR101808751B1 (ko) * | 2009-11-13 | 2017-12-13 | 그리폴스 테라퓨틱스 인코포레이티드 | 폰 빌레브란트 인자(ｖＷＦ)-함유 제제, 및 그와 관련된 방법, 키트 및 용도 |
| US20130040888A1 (en) | 2010-02-16 | 2013-02-14 | Novo Nordisk A/S | Factor VIII Molecules With Reduced VWF Binding |
| JP5826772B2 (ja) | 2010-02-16 | 2015-12-02 | ノヴォ ノルディスク アー／エス | コンジュゲートタンパク質 |
| CN105153313A (zh) | 2010-02-16 | 2015-12-16 | 诺沃—诺迪斯克有限公司 | 因子viii融合蛋白 |
| US8859731B2 (en) | 2010-04-21 | 2014-10-14 | Novo Nordisk A/S | Selective modification of proteins |
| JP2013532176A (ja) | 2010-07-15 | 2013-08-15 | ノヴォ ノルディスク アー／エス | 安定化させた第ｖｉｉｉ因子バリアント |
| CN102161692B (zh) * | 2011-03-08 | 2013-10-02 | 中国人民解放军第三军医大学 | 改造的止血多肽及其运用 |
| JP2015515482A (ja) | 2012-04-24 | 2015-05-28 | ノヴォ ノルディスク アー／エス | 血友病の治療に適する化合物 |
| EP2662083A1 (en) * | 2012-05-08 | 2013-11-13 | CSL Behring GmbH | Sugar compositions for treating hemophilia a and/or von willebrand disease |
| EP2796145B1 (en) * | 2013-04-22 | 2017-11-01 | CSL Ltd. | A covalent complex of von willebrand factor and faktor viii linked by a disulphide bridge |
| WO2014198699A2 (en) * | 2013-06-12 | 2014-12-18 | Novo Nordisk A/S | Compounds suitable for treatment of haemophilia |
-
2016
- 2016-03-04 ES ES16712738T patent/ES2772933T3/es active Active
- 2016-03-04 US US15/555,894 patent/US11155601B2/en active Active
- 2016-03-04 SG SG11201706659WA patent/SG11201706659WA/en unknown
- 2016-03-04 BR BR112017018468-0A patent/BR112017018468A2/pt not_active Application Discontinuation
- 2016-03-04 CN CN201680014025.4A patent/CN107406493B/zh active Active
- 2016-03-04 JP JP2017564946A patent/JP2018510212A/ja not_active Ceased
- 2016-03-04 KR KR1020177028206A patent/KR20170125941A/ko not_active Withdrawn
- 2016-03-04 AU AU2016231327A patent/AU2016231327B2/en not_active Ceased
- 2016-03-04 DK DK16712738.0T patent/DK3265483T3/da active
- 2016-03-04 WO PCT/EP2016/054647 patent/WO2016142288A1/en not_active Ceased
- 2016-03-04 CA CA2978374A patent/CA2978374A1/en not_active Abandoned
- 2016-03-04 EP EP16712738.0A patent/EP3265483B1/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| BR112017018468A2 (pt) | 2018-04-17 |
| JP2018510212A (ja) | 2018-04-12 |
| KR20170125941A (ko) | 2017-11-15 |
| AU2016231327B2 (en) | 2018-08-09 |
| EP3265483A1 (en) | 2018-01-10 |
| CN107406493B (zh) | 2021-08-13 |
| HK1244292A1 (en) | 2018-08-03 |
| US11155601B2 (en) | 2021-10-26 |
| US20180051067A1 (en) | 2018-02-22 |
| DK3265483T3 (da) | 2020-03-02 |
| AU2016231327A1 (en) | 2017-10-26 |
| EP3265483B1 (en) | 2019-12-11 |
| WO2016142288A1 (en) | 2016-09-15 |
| CN107406493A (zh) | 2017-11-28 |
| CA2978374A1 (en) | 2016-09-15 |
| SG11201706659WA (en) | 2017-09-28 |
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