ES2908008T3 - Polipéptidos truncados del Factor de von Willebrand para su administración extravascular en el tratamiento o profilaxis de un trastorno de la coagulación sanguínea - Google Patents
Polipéptidos truncados del Factor de von Willebrand para su administración extravascular en el tratamiento o profilaxis de un trastorno de la coagulación sanguínea Download PDFInfo
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- ES2908008T3 ES2908008T3 ES17801644T ES17801644T ES2908008T3 ES 2908008 T3 ES2908008 T3 ES 2908008T3 ES 17801644 T ES17801644 T ES 17801644T ES 17801644 T ES17801644 T ES 17801644T ES 2908008 T3 ES2908008 T3 ES 2908008T3
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Classifications
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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)
-
- 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
-
- 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
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- 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)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Toxicology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP16198497 | 2016-11-11 | ||
| PCT/EP2017/078840 WO2018087271A1 (en) | 2016-11-11 | 2017-11-10 | Truncated von willebrand factor polypeptides for extravascular administration in the treatment or prophylaxis of a blood coagulation disorder |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2908008T3 true ES2908008T3 (es) | 2022-04-27 |
Family
ID=57389201
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES17801644T Active ES2908008T3 (es) | 2016-11-11 | 2017-11-10 | Polipéptidos truncados del Factor de von Willebrand para su administración extravascular en el tratamiento o profilaxis de un trastorno de la coagulación sanguínea |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US11890327B2 (https=) |
| EP (1) | EP3538134B1 (https=) |
| JP (1) | JP2020504082A (https=) |
| KR (1) | KR20190073576A (https=) |
| CN (1) | CN110381986B (https=) |
| AU (1) | AU2017358865A1 (https=) |
| CA (1) | CA3043397A1 (https=) |
| DK (1) | DK3538134T3 (https=) |
| ES (1) | ES2908008T3 (https=) |
| SG (2) | SG11201903954WA (https=) |
| TW (1) | TW201828974A (https=) |
| WO (1) | WO2018087271A1 (https=) |
Families Citing this family (5)
| 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 |
| BR112020022164A2 (pt) | 2018-05-18 | 2021-02-02 | Bioverativ Therapeutics Inc. | métodos de tratamento de hemofilia a |
| 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 |
| KR102647642B1 (ko) * | 2021-05-04 | 2024-03-15 | (주)케어젠 | 혈액 응고 활성을 갖는 펩타이드와 이의 용도 |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| AU2353384A (en) | 1983-01-19 | 1984-07-26 | Genentech Inc. | Amplification in eukaryotic host cells |
| US4713339A (en) | 1983-01-19 | 1987-12-15 | Genentech, Inc. | Polycistronic expression vector construction |
| US4970300A (en) | 1985-02-01 | 1990-11-13 | New York University | Modified factor VIII |
| AU6029594A (en) | 1993-01-15 | 1994-08-15 | Enzon, Inc. | Factor viii - polymeric conjugates |
| SE504074C2 (sv) | 1993-07-05 | 1996-11-04 | Pharmacia Ab | Proteinberedning för subkutan, intramuskulär eller intradermal administrering |
| IL113010A0 (en) | 1994-03-31 | 1995-10-31 | Pharmacia Ab | Pharmaceutical formulation comprising factor VIII or factor ix with an activity of at least 200 IU/ml and an enhancer for improved subcutaneous intramuscular or intradermal administration |
| JPH11501506A (ja) | 1994-12-12 | 1999-02-09 | ベス イスラエル デアコネス メディカル センター | キメラ型サイトカインおよびその利用 |
| 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 |
| AT403764B (de) * | 1996-03-15 | 1998-05-25 | Immuno Ag | Stabiler faktor viii/vwf-komplex |
| PT1754718E (pt) | 1996-04-24 | 2011-07-13 | Univ Michigan | Factor viii resistente à inactivação |
| US20040092442A1 (en) | 1996-04-24 | 2004-05-13 | University Of Michigan | Inactivation resistant factor VIII |
| 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 |
| US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| US6887470B1 (en) | 1999-09-10 | 2005-05-03 | Conjuchem, Inc. | Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components |
| 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 |
| US20080108560A1 (en) | 2002-03-05 | 2008-05-08 | Eli Lilly And Company | Heterologous G-Csf Fusion Proteins |
| DE60332011D1 (de) | 2002-04-29 | 2010-05-20 | Sanquin Bloedvoorziening | Antagonisten der interaktion zwischen faktor viii und lrp ("low-density lipoprotein receptor related protein") |
| 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 |
| TWI353991B (en) | 2003-05-06 | 2011-12-11 | Syntonix Pharmaceuticals Inc | Immunoglobulin chimeric monomer-dimer hybrids |
| PT1624891E (pt) | 2003-05-06 | 2010-01-05 | Syntonix Pharmaceuticals Inc | Proteínas quiméricas de factor de coagulação-fc destinadas ao tratamento da hemofilia |
| MXPA05013565A (es) | 2003-06-12 | 2006-03-09 | Lilly Co Eli | Proteinas de fusion analogas al glp-1. |
| JP2008504008A (ja) | 2003-12-31 | 2008-02-14 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | 改良された薬物動態を有するＦｃ−エリスロポエチン融合タンパク質 |
| US7670595B2 (en) | 2004-06-28 | 2010-03-02 | Merck Patent Gmbh | Fc-interferon-beta fusion proteins |
| 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 |
| EP1816201A1 (en) | 2006-02-06 | 2007-08-08 | CSL Behring GmbH | Modified coagulation factor VIIa with extended half-life |
| CA2647314A1 (en) | 2006-03-31 | 2007-11-08 | Baxter International Inc. | Pegylated factor viii |
| AU2007260185B2 (en) | 2006-06-14 | 2013-01-31 | Csl Behring Gmbh | Proteolytically cleavable fusion protein comprising a blood coagulation factor |
| AU2007338298B2 (en) | 2006-12-22 | 2013-02-07 | Csl Behring Gmbh | Modified coagulation factors with prolonged in vivo half-life |
| 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 |
| KR101648734B1 (ko) | 2008-06-24 | 2016-08-18 | 체에스엘 베링 게엠베하 | 연장된 생체내 반감기를 갖는 인자 ｖｉｉｉ, 폰 빌레브란트 인자 또는 이들의 복합체 |
| KR101808751B1 (ko) | 2009-11-13 | 2017-12-13 | 그리폴스 테라퓨틱스 인코포레이티드 | 폰 빌레브란트 인자(ｖＷＦ)-함유 제제, 및 그와 관련된 방법, 키트 및 용도 |
| WO2013093760A2 (en) | 2011-12-19 | 2013-06-27 | Grifols, S.A. | Compositions, methods, and kits for preparing sialylated recombinant proteins |
| DK2804623T3 (da) | 2012-01-12 | 2019-11-11 | Bioverativ Therapeutics Inc | Kimære faktor viii-polypeptider og anvendelser deraf |
| WO2013120939A1 (en) | 2012-02-15 | 2013-08-22 | Csl Behring Gmbh | Von willebrand factor variants having improved factor viii binding affinity |
| EP2841091A1 (en) * | 2012-04-24 | 2015-03-04 | Novo Nordisk A/S | Pharmaceutical composition suitable for treatment of haemophilia |
| 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 |
| HRP20200007T1 (hr) | 2012-07-11 | 2020-03-20 | Bioverativ Therapeutics Inc. | Kompleks proteina faktora viii s xten i von willebrandovim faktorom, te njegova uporaba |
| 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 |
| EP3152230B1 (en) | 2014-06-06 | 2019-08-07 | Octapharma AG | Preparation comprising factor viii and von willebrand factor peptides |
| CA2953593C (en) | 2014-07-02 | 2023-09-26 | Csl Limited | Modified von willebrand factor |
| WO2016188905A1 (en) | 2015-05-22 | 2016-12-01 | Csl Behring Recombinant Facility Ag | Methods for preparing modified von willebrand factor |
-
2017
- 2017-11-10 CA CA3043397A patent/CA3043397A1/en not_active Abandoned
- 2017-11-10 AU AU2017358865A patent/AU2017358865A1/en not_active Abandoned
- 2017-11-10 DK DK17801644.0T patent/DK3538134T3/da active
- 2017-11-10 EP EP17801644.0A patent/EP3538134B1/en active Active
- 2017-11-10 CN CN201780069945.0A patent/CN110381986B/zh active Active
- 2017-11-10 SG SG11201903954WA patent/SG11201903954WA/en unknown
- 2017-11-10 SG SG10201912768YA patent/SG10201912768YA/en unknown
- 2017-11-10 US US16/349,002 patent/US11890327B2/en active Active
- 2017-11-10 KR KR1020197016644A patent/KR20190073576A/ko not_active Withdrawn
- 2017-11-10 WO PCT/EP2017/078840 patent/WO2018087271A1/en not_active Ceased
- 2017-11-10 JP JP2019524345A patent/JP2020504082A/ja active Pending
- 2017-11-10 ES ES17801644T patent/ES2908008T3/es active Active
- 2017-11-10 TW TW106139051A patent/TW201828974A/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA3043397A1 (en) | 2018-05-17 |
| JP2020504082A (ja) | 2020-02-06 |
| CN110381986A (zh) | 2019-10-25 |
| TW201828974A (zh) | 2018-08-16 |
| DK3538134T3 (da) | 2022-02-07 |
| WO2018087271A1 (en) | 2018-05-17 |
| EP3538134A1 (en) | 2019-09-18 |
| SG10201912768YA (en) | 2020-02-27 |
| KR20190073576A (ko) | 2019-06-26 |
| AU2017358865A1 (en) | 2019-05-09 |
| SG11201903954WA (en) | 2019-05-30 |
| EP3538134B1 (en) | 2021-12-29 |
| CN110381986B (zh) | 2023-08-18 |
| US20210268071A1 (en) | 2021-09-02 |
| US11890327B2 (en) | 2024-02-06 |
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