AR035786A2 - Variantes de factores de coagulacion dependientes de vitamina k y composiciones que los contienen - Google Patents
Variantes de factores de coagulacion dependientes de vitamina k y composiciones que los contienenInfo
- Publication number
- AR035786A2 AR035786A2 ARP020101003A ARP020101003A AR035786A2 AR 035786 A2 AR035786 A2 AR 035786A2 AR P020101003 A ARP020101003 A AR P020101003A AR P020101003 A ARP020101003 A AR P020101003A AR 035786 A2 AR035786 A2 AR 035786A2
- Authority
- AR
- Argentina
- Prior art keywords
- amino acid
- vitamin
- gla domain
- protein
- modified gla
- Prior art date
Links
Classifications
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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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/52—Genes encoding for enzymes or proenzymes
-
- 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
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6437—Coagulation factor VIIa (3.4.21.21)
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- 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
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
-
- 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
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/644—Coagulation factor IXa (3.4.21.22)
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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
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6464—Protein C (3.4.21.69)
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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
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/647—Blood coagulation factors not provided for in a preceding group or according to more than one of the proceeding groups
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21021—Coagulation factor VIIa (3.4.21.21)
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21022—Coagulation factor IXa (3.4.21.22)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21069—Protein C activated (3.4.21.69)
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- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Se describen: polipéptidos dependientes de vitamina K que incluye un dominio GLA modificado que aumenta la afinidad de unión del polipéptido con las membranas con respecto al correspondiente polipéptido nativo dependiente de vitamina K. El dominio GLA modificado puede incluir por lo menos una sustitución de amino ácido. Por ejemplo, la sustitución de amino ácido puede ser en el amino ácido 11, 12, 29, 33 o 34. El dominio GLA modificado, puede incluir una secuencia de amino ácidos que, en el estado saturado de calcio, forma una estructura terciaria que tiene un núcleo catiónico con un halo de carga electro-negativa. El polipéptido dependiente de vitamina K, puede ser por ejemplo, proteína C, proteína C actividad, factor IX, factor IXa, factor VII, factor VIIa o factor VIIa de sitio activo modificado. El dominio GLA modificado de la proteína C o la proteína C activada puede incluir un residuo ácido glutámico en el amino ácido 33 y un residuo ácido aspártico en el amino ácido 34. El dominio GLA modificado de la proteína C o de la proteína C activada, puede también incluir un residuo glutamina o ácido glutámico en el amino ácido 11. Adicionalmente, un residuo glicina puede ser sustituido en el amino ácido 12 en el dominio GLA de la proteína C o de la proteína C activada. El dominio GLA modificado del factor VII, el factor VIIa y el factor VIIa de sitio activo modificado puede contener una sustitución en el amino ácido 11 y 33. Por ejemplo, un residuo glutamina en el amino ácido 11 y un residuo ácido glutámico en el amino ácido 33, pueden estar sustituidos. Un ácido nucleico aislado que codifica una polipéptido dependiente de vitamina K que contiene un dominio GLA modificado tal como se describe arriba. Además, la presente se refiere también a una célula hospedante de mamífero que incluye un vector ácido nucleico que codifica un polipéptido dependiente de vitamina K que contiene un dominio GLA modificado según se describe arriba. Una composición farmacéutica que incluye un vehículo farmacéuticamente aceptable y una cantidad de un polipéptido dependiente de vitamina K efectiva para inhibir o incrementar la formación de coágulos en un mamífero, donde el polipéptido dependiente de vitamina K incluye un dominio GLA modificado como se ha descripto anteriormente. Un polipéptido dependiente de la vitamina K para ser utilizado en el tratamiento de una trastorno relacionado con la coagulación o en la manufactura de un medicamento para el tratamiento de un trastorno de coagulación. Métodos para incrementar o disminuir la formación de coágulos en un mamífero.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/955,636 US6017882A (en) | 1997-10-23 | 1997-10-23 | Modified vitamin K-dependent polypeptides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR035786A2 true AR035786A2 (es) | 2004-07-14 |
Family
ID=25497114
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP980105278A AR020048A1 (es) | 1997-10-23 | 1998-10-22 | Un polipeptido dependiente de la vitamina k, una composicion farmaceutica que lo comprende, el uso del mismo para la manufactura de un medicamento, unacido nucleico aislado que codifica a dicho polipeptido y una celula hospedante de mamifero. |
| ARP020101003A AR035786A2 (es) | 1997-10-23 | 2002-03-20 | Variantes de factores de coagulacion dependientes de vitamina k y composiciones que los contienen |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP980105278A AR020048A1 (es) | 1997-10-23 | 1998-10-22 | Un polipeptido dependiente de la vitamina k, una composicion farmaceutica que lo comprende, el uso del mismo para la manufactura de un medicamento, unacido nucleico aislado que codifica a dicho polipeptido y una celula hospedante de mamifero. |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US6017882A (es) |
| EP (2) | EP1676919B1 (es) |
| JP (1) | JP4276379B2 (es) |
| KR (1) | KR20010031370A (es) |
| CN (1) | CN1246462C (es) |
| AP (1) | AP2000001811A0 (es) |
| AR (2) | AR020048A1 (es) |
| AT (1) | ATE390486T1 (es) |
| AU (1) | AU749279C (es) |
| BR (1) | BR9814611A (es) |
| CA (1) | CA2307175C (es) |
| DE (1) | DE69839313T2 (es) |
| DK (1) | DK1090128T3 (es) |
| EA (1) | EA200000449A1 (es) |
| ES (2) | ES2303362T3 (es) |
| HR (1) | HRP20000234A2 (es) |
| HU (1) | HU225993B1 (es) |
| ID (1) | ID26330A (es) |
| IL (1) | IL135603A0 (es) |
| IS (1) | IS5449A (es) |
| MY (1) | MY136336A (es) |
| NO (1) | NO20002025L (es) |
| NZ (1) | NZ504114A (es) |
| PL (1) | PL194194B1 (es) |
| PT (1) | PT1090128E (es) |
| SG (1) | SG105547A1 (es) |
| TR (1) | TR200001105T2 (es) |
| TW (1) | TW587081B (es) |
| WO (1) | WO1999020767A1 (es) |
| ZA (1) | ZA989597B (es) |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6693075B1 (en) | 1997-10-23 | 2004-02-17 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US6747003B1 (en) | 1997-10-23 | 2004-06-08 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US7247708B2 (en) * | 1997-10-23 | 2007-07-24 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US6998122B1 (en) | 1999-04-30 | 2006-02-14 | Eli Lilly And Company | Protein C derivatives |
| EP1237917A2 (en) * | 1999-11-19 | 2002-09-11 | Eli Lilly And Company | Protein c derivatives |
| CA2399267A1 (en) | 2000-02-02 | 2001-08-09 | Eli Lilly And Company | Protein c derivatives |
| US6630138B2 (en) | 2000-02-11 | 2003-10-07 | Eli Lilly And Company | Protein C derivatives |
| US6806063B2 (en) * | 2000-02-11 | 2004-10-19 | Maxygen Aps | Factor VII or VIIa-like molecules |
| US7220837B1 (en) | 2000-04-28 | 2007-05-22 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US7812132B2 (en) * | 2000-04-28 | 2010-10-12 | Regents Of The University Of Minnesota | Modified vitamin K-dependent polypeptides |
| US20030211094A1 (en) * | 2001-06-26 | 2003-11-13 | Nelsestuen Gary L. | High molecular weight derivatives of vitamin k-dependent polypeptides |
| US7160540B2 (en) * | 2000-06-30 | 2007-01-09 | Regents Of The University Of Minnesota | Methods for detecting activity of clottings factors |
| US6423826B1 (en) | 2000-06-30 | 2002-07-23 | Regents Of The University Of Minnesota | High molecular weight derivatives of vitamin K-dependent polypeptides |
| EP1320371A2 (en) * | 2000-07-31 | 2003-06-25 | Ottawa Heart Institute Research Corporation | Charged phospholipid compositions and methods for their use |
| US6933367B2 (en) | 2000-10-18 | 2005-08-23 | Maxygen Aps | Protein C or activated protein C-like molecules |
| CA2440092A1 (en) * | 2001-03-02 | 2002-09-12 | T.A.C. Thrombosis And Coagulation Ab | Protein c variants |
| JP2005518801A (ja) * | 2002-03-01 | 2005-06-30 | テイ・エイ・シー・スロムボシス・アンド・コアグラシヨン・アクテイエボラーク | 組換えプロテインｃバリアント |
| US20030186862A1 (en) * | 2002-04-02 | 2003-10-02 | Nelsestuen Gary L. | Factor VIIa compositions |
| SI1499719T1 (sl) | 2002-04-30 | 2011-03-31 | Bayer Healthcare Llc | Polipeptidne variante faktorja VII ali VIIa |
| US20030232075A1 (en) * | 2002-05-06 | 2003-12-18 | University Of Minnesota, A Minnesota Corporation | Compositions for producing factor Xa |
| ES2523655T5 (es) | 2002-06-21 | 2018-04-23 | Novo Nordisk Health Care Ag | Composiciones sólidas estabilizadas de polipéptidos del Factor VIIa |
| US20040176704A1 (en) * | 2003-03-04 | 2004-09-09 | Stevens Timothy A | Collection device adapted to accept cartridge for point of care system |
| WO2004083421A1 (en) | 2003-03-18 | 2004-09-30 | Novo Nordisk Health Care Ag | Method for the production of gla-residue containing serine proteases |
| ATE431403T1 (de) * | 2003-03-20 | 2009-05-15 | Bayer Healthcare Llc | Fvii oder fviia varianten |
| DK1644504T3 (da) * | 2003-06-19 | 2010-05-25 | Bayer Healthcare Llc | Faktor VII- eller -VIIA-Gla-domænevarianter |
| ATE547519T1 (de) | 2003-09-09 | 2012-03-15 | Novo Nordisk Healthcare Ag | Gerinnungsfaktor-vii-polypeptide |
| KR100755967B1 (ko) * | 2003-10-23 | 2007-09-06 | 한국타이어 주식회사 | 타이어의 비드와 휠의 갭 측정장치 |
| CN102351953B (zh) | 2003-12-01 | 2017-05-10 | 诺和诺德医疗保健公司 | 液体因子vii组合物的病毒过滤 |
| TR201809670T4 (tr) | 2003-12-19 | 2018-07-23 | Novo Nordisk Healthcare Ag | Faktör VII polipeptitlerinin stabilize edilmiş kompozisyonları. |
| EP2368579A1 (en) | 2004-01-21 | 2011-09-28 | Novo Nordisk Health Care AG | Transglutaminase mediated conjugation of peptides |
| EP2360171A1 (en) | 2004-12-23 | 2011-08-24 | Novo Nordisk Health Care AG | Reduction of the content of protein contaminants in compositions comprising a vitamin K-dependent protein of interest |
| US8206750B2 (en) | 2005-03-24 | 2012-06-26 | Cerenis Therapeutics Holding S.A. | Charged lipoprotein complexes and their uses |
| US20080188400A1 (en) * | 2005-04-26 | 2008-08-07 | Maxygen Holdings Ltd. | Methods For Treating Bleeding |
| JP5335422B2 (ja) | 2005-06-17 | 2013-11-06 | ノボ ノルディスク ヘルス ケア アクチェンゲゼルシャフト | 少なくとも１つの非天然のシステインを含んでいる操作されたタンパク質の選択的な還元および誘導体化 |
| JP5147692B2 (ja) | 2005-07-13 | 2013-02-20 | ノボ ノルディスク ヘルス ケア アーゲー | 治療用タンパク質生成のための宿主細胞タンパク質ノックアウト細胞 |
| WO2007026021A1 (en) | 2005-09-01 | 2007-03-08 | Novo Nordisk Health Care Ag | Hydrophobic interaction chromatography purification of factor vii polypeptides |
| EP2316930A1 (en) | 2005-09-14 | 2011-05-04 | Novo Nordisk Health Care AG | Human coagulation factor VII polypeptides |
| ES2531934T3 (es) | 2006-09-01 | 2015-03-20 | Novo Nordisk Health Care Ag | Glicoproteínas modificadas |
| JP2010513462A (ja) * | 2006-12-20 | 2010-04-30 | バイエル・ヘルスケア・エルエルシー | 第ＶＩＩおよび第ＶＩＩａ因子組成物 |
| US20100166729A9 (en) | 2007-04-13 | 2010-07-01 | Madison Edwin L | Modified factor VII polypeptides and uses thereof |
| US20080305157A1 (en) * | 2007-06-08 | 2008-12-11 | University Of Maryland Office Of Technology Commercialization | Encapsulation and separation of charged organic solutes inside catanionic vesicles |
| NZ586250A (en) | 2007-12-27 | 2012-11-30 | Baxter Int | Cell culture processes |
| TWI538916B (zh) | 2008-04-11 | 2016-06-21 | 介控生化科技公司 | 經修飾的因子vii多肽和其用途 |
| EP3266463B1 (en) | 2009-06-09 | 2023-12-13 | Prolong Pharmaceuticals, LLC | Hemoglobin compositions |
| EP2514760B1 (en) * | 2009-12-14 | 2015-10-21 | National University Corporation Hokkaido University | Peptides imparting cell permeability to lipid membrane structure |
| TWI557135B (zh) | 2010-11-03 | 2016-11-11 | 介控生化科技公司 | 經修飾之第九因子多胜肽及其用途 |
| ES2704083T3 (es) | 2012-07-25 | 2019-03-14 | Catalyst Biosciences Inc | Polipéptidos de factor x modificados y usos de los mismos |
| US11491212B1 (en) | 2017-09-27 | 2022-11-08 | Catalyst Biosciences, Inc. | Subcutaneous administration of modified factor IX polypeptides and treatment of hemophilia B |
| CN114728044A (zh) | 2019-08-15 | 2022-07-08 | 介控生化科技公司 | 用于皮下施用和按需求治疗的经修饰的因子vii多肽 |
| WO2021154414A2 (en) | 2020-01-29 | 2021-08-05 | Catalyst Biosciences, Inc. | Gene therapy for hemophilia b with a chimeric aav capsid vector encoding modified factor ix polypeptides |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0296413A2 (en) * | 1987-06-12 | 1988-12-28 | Hoechst Japan Limited | Hybrid protein C and method for its preparation |
| JPH0246296A (ja) * | 1988-08-09 | 1990-02-15 | Hoechst Japan Ltd | 雑種プロテインｃ及びその製造方法 |
| US5580560A (en) * | 1989-11-13 | 1996-12-03 | Novo Nordisk A/S | Modified factor VII/VIIa |
| EP0521873B1 (en) * | 1990-01-29 | 1999-06-02 | Zymogenetics, Inc. | Anticoagulant proteins |
| US5504064A (en) * | 1991-04-10 | 1996-04-02 | Oklahoma Medical Research Foundation | Treatment of bleeding with modified tissue factor in combination with an activator of FVII |
-
1997
- 1997-10-23 US US08/955,636 patent/US6017882A/en not_active Expired - Lifetime
-
1998
- 1998-10-20 EP EP05026205.4A patent/EP1676919B1/en not_active Expired - Lifetime
- 1998-10-20 HU HU0102257A patent/HU225993B1/hu not_active IP Right Cessation
- 1998-10-20 NZ NZ504114A patent/NZ504114A/xx unknown
- 1998-10-20 PT PT98967009T patent/PT1090128E/pt unknown
- 1998-10-20 AT AT98967009T patent/ATE390486T1/de active
- 1998-10-20 IL IL13560398A patent/IL135603A0/xx unknown
- 1998-10-20 ES ES98967009T patent/ES2303362T3/es not_active Expired - Lifetime
- 1998-10-20 DE DE69839313T patent/DE69839313T2/de not_active Expired - Lifetime
- 1998-10-20 JP JP2000517087A patent/JP4276379B2/ja not_active Expired - Fee Related
- 1998-10-20 BR BR9814611-4A patent/BR9814611A/pt active Search and Examination
- 1998-10-20 AU AU27024/99A patent/AU749279C/en not_active Ceased
- 1998-10-20 PL PL98340284A patent/PL194194B1/pl unknown
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2000
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