NZ520799A - Modified factor VIII - Google Patents
Modified factor VIIIInfo
- Publication number
- NZ520799A NZ520799A NZ520799A NZ52079901A NZ520799A NZ 520799 A NZ520799 A NZ 520799A NZ 520799 A NZ520799 A NZ 520799A NZ 52079901 A NZ52079901 A NZ 52079901A NZ 520799 A NZ520799 A NZ 520799A
- Authority
- NZ
- New Zealand
- Prior art keywords
- seq
- porcine
- factor
- domain
- human
- Prior art date
Links
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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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S930/00—Peptide or protein sequence
- Y10S930/01—Peptide or protein sequence
- Y10S930/10—Factor VIII, AHF; related peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
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- Hematology (AREA)
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- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Glass Compositions (AREA)
- Fish Paste Products (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/523,656 US6458563B1 (en) | 1996-06-26 | 2000-03-10 | Modified factor VIII |
| PCT/US2001/005076 WO2001068109A1 (en) | 2000-03-10 | 2001-02-16 | Modified factor viii |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ520799A true NZ520799A (en) | 2004-06-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ520799A NZ520799A (en) | 2000-03-10 | 2001-02-16 | Modified factor VIII |
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|---|---|
| US (3) | US6458563B1 (OSRAM) |
| EP (1) | EP1280540B1 (OSRAM) |
| JP (1) | JP4044337B2 (OSRAM) |
| KR (1) | KR100485525B1 (OSRAM) |
| CN (1) | CN1191360C (OSRAM) |
| AT (1) | ATE391512T1 (OSRAM) |
| AU (2) | AU2001238416B2 (OSRAM) |
| BE (1) | BE2016C024I2 (OSRAM) |
| BR (2) | BRPI0109131B8 (OSRAM) |
| CA (1) | CA2400295C (OSRAM) |
| CY (2) | CY1108179T1 (OSRAM) |
| CZ (1) | CZ298250B6 (OSRAM) |
| DE (1) | DE60133541T2 (OSRAM) |
| DK (1) | DK1280540T3 (OSRAM) |
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| ES (1) | ES2304379T3 (OSRAM) |
| FR (1) | FR16C0016I2 (OSRAM) |
| HU (2) | HU227804B1 (OSRAM) |
| IL (2) | IL151371A0 (OSRAM) |
| LT (1) | LTC1280540I2 (OSRAM) |
| LU (1) | LU93049I2 (OSRAM) |
| ME (1) | ME00601B (OSRAM) |
| MX (1) | MXPA02008798A (OSRAM) |
| NL (1) | NL300808I2 (OSRAM) |
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| NZ (1) | NZ520799A (OSRAM) |
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| PT (1) | PT1280540E (OSRAM) |
| RS (1) | RS50364B (OSRAM) |
| RU (1) | RU2285724C2 (OSRAM) |
| SI (1) | SI1280540T1 (OSRAM) |
| SK (1) | SK286205B6 (OSRAM) |
| UA (1) | UA75064C2 (OSRAM) |
| WO (1) | WO2001068109A1 (OSRAM) |
| ZA (1) | ZA200206810B (OSRAM) |
Families Citing this family (99)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7560107B2 (en) * | 1996-06-26 | 2009-07-14 | Emory University | Modified factor VIII |
| 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 |
| AU2002337901B2 (en) * | 2001-10-05 | 2008-01-17 | Expression Therapeutics Llc | Nucleic acid and amino acid sequences encoding high-level expressor factor VIII polypeptides and methods of use |
| WO2003047507A2 (en) * | 2001-11-30 | 2003-06-12 | Emory University | Factor viii c2 domain variants |
| GB0207092D0 (en) | 2002-03-26 | 2002-05-08 | Sod Conseils Rech Applic | Stable pharmaceutical composition containing factor VIII |
| TWI353991B (en) | 2003-05-06 | 2011-12-11 | Syntonix Pharmaceuticals Inc | Immunoglobulin chimeric monomer-dimer hybrids |
| US7498024B2 (en) * | 2003-06-03 | 2009-03-03 | Cell Genesys, Inc. | Compositions and methods for enhanced expression of immunoglobulins from a single vector using a peptide cleavage site |
| US7485291B2 (en) * | 2003-06-03 | 2009-02-03 | Cell Genesys, Inc. | Compositions and methods for generating multiple polypeptides from a single vector using a virus derived peptide cleavage site, and uses thereof |
| DE602004007924T2 (de) * | 2003-06-26 | 2008-04-10 | Merck Patent Gmbh | Thrombopoietinproteine mit verbesserten eigenschaften |
| US20050059023A1 (en) * | 2003-09-16 | 2005-03-17 | Cantor Thomas L. | Methods and kits for monitoring resistance to therapeutic agents |
| US7211559B2 (en) | 2003-10-31 | 2007-05-01 | University Of Maryland, Baltimore | Factor VIII compositions and methods |
| AU2004296768B2 (en) * | 2003-12-03 | 2010-06-24 | University Of Rochester | Recombinant factor VIII having increased specific activity |
| WO2005107776A1 (en) * | 2004-05-03 | 2005-11-17 | Emory University | METHOD OF ADMINISTERING PORCINE B-DOMAINLESS fVIII |
| WO2005123928A1 (en) * | 2004-06-08 | 2005-12-29 | Battelle Memorial Institute | Production of human coagulation factor viii from plant cells and whole plants |
| CN101124331B (zh) * | 2004-11-12 | 2013-04-24 | 拜尔健康护理有限责任公司 | Fvⅲ的位点定向修饰 |
| WO2006063031A2 (en) * | 2004-12-06 | 2006-06-15 | Haplomics | Allelic variants of human factor viii |
| US7855279B2 (en) | 2005-09-27 | 2010-12-21 | Amunix Operating, Inc. | Unstructured recombinant polymers and uses thereof |
| JP2009518345A (ja) | 2005-12-07 | 2009-05-07 | テフニーシェ ウニヴェルジテート ミュンヘン | 因子ｖｉｉｉおよび因子ｖｉｉｉ様タンパク質に対する小型ペプチドおよびペプチド模倣物の親和性リガンド |
| EP1816201A1 (en) | 2006-02-06 | 2007-08-08 | CSL Behring GmbH | Modified coagulation factor VIIa with extended half-life |
| ATE474917T1 (de) * | 2006-04-11 | 2010-08-15 | Csl Behring Gmbh | Verfahren zur erhöhung der in-vivo-gewinnung therapeutischer polypeptide |
| US7939632B2 (en) * | 2006-06-14 | 2011-05-10 | Csl Behring Gmbh | Proteolytically cleavable fusion proteins with high molar specific activity |
| EP1935430A1 (en) * | 2006-12-22 | 2008-06-25 | CSL Behring GmbH | Modified coagulation factors with prolonged in vivo half-life |
| EP2097096B1 (en) | 2006-12-22 | 2017-05-31 | CSL Behring GmbH | Modified coagulation factors with prolonged in vivo half-life |
| FR2913020B1 (fr) * | 2007-02-23 | 2012-11-23 | Biomethodes | Nouveaux facteurs viii pour le traitement des hemophiles de type a |
| EP1988101A1 (en) * | 2007-05-04 | 2008-11-05 | Novo Nordisk A/S | Improvement of factor VIII polypeptide titers in cell cultures |
| EP2209908B1 (en) | 2007-11-01 | 2014-09-03 | University Of Rochester | Recombinant factor viii having increased stability |
| EP2149603A1 (en) | 2008-07-28 | 2010-02-03 | DRK-Blutspendedienst Baden-Württemberg-Hessen gGmbH | Factor IX variants with clotting activity in absence of their cofactor and their use for treating bleeding disorders |
| MX362028B (es) | 2009-02-03 | 2019-01-04 | Amunix Pharmaceuticals Inc | Polipeptidos recombinantes extendidos y composiciones que comprenden los mismos. |
| DK3266463T3 (da) | 2009-06-09 | 2024-01-08 | Prolong Pharmaceuticals Llc | Hæmoglobinsammensætninger |
| BR112012004094A2 (pt) | 2009-08-24 | 2016-03-08 | Amunix Operating Inc | composições de fator vii de coagulação e métodos para fazer e usar as mesmas |
| EP2498804A4 (en) * | 2009-11-13 | 2013-05-08 | Puget Sound Blood Ct | FACTOR VIII B CELL EPITOPARIANTS WITH REDUCED IMMUNOGENITY |
| EP3326643B1 (en) | 2009-12-06 | 2021-04-07 | Bioverativ Therapeutics Inc. | Factor viii-fc chimeric and hybrid polypeptides, and methods of use thereof |
| WO2011088391A2 (en) * | 2010-01-14 | 2011-07-21 | Haplomics, Inc. | Predicting and reducing alloimmunogenicity of protein therapeutics |
| US9611310B2 (en) | 2010-07-09 | 2017-04-04 | Bioverativ Therapeutics Inc. | Systems for factor VIII processing and methods thereof |
| CA2804280A1 (en) | 2010-07-09 | 2012-01-12 | Biogen Idec Hemophilia Inc. | Chimeric clotting factors |
| EP2635297B1 (en) | 2010-11-05 | 2019-02-27 | Baxalta GmbH | A new variant of antihemophilic factor viii having increased specific activity |
| WO2012094532A1 (en) * | 2011-01-05 | 2012-07-12 | Expression Therapeutics, Llc | Method and system for suspension cell culture |
| PL2717898T3 (pl) | 2011-06-10 | 2019-06-28 | Bioverativ Therapeutics Inc. | Związki o działaniu prokoagulacyjnym i sposoby ich stosowania |
| TWI764092B (zh) | 2011-07-08 | 2022-05-11 | 美商百歐維拉提夫治療公司 | 因子viii嵌合及雜交多肽，及其使用方法 |
| EA028914B1 (ru) | 2011-07-25 | 2018-01-31 | Байоджен Хемофилия Инк. | Исследования для мониторинга нарушений свертываемости крови |
| CN102277379B (zh) * | 2011-08-18 | 2013-07-24 | 中国科学院遗传与发育生物学研究所 | 表达凝血因子viii的表达载体及其应用 |
| TR201816253T4 (tr) | 2012-01-12 | 2018-11-21 | Bioverativ Therapeutics Inc | Faktör VIII terapisi almakta olan bireylerde faktör VIII'e karşı immünojenisiteyi azaltmanın yöntemleri. |
| US11370827B2 (en) | 2012-01-12 | 2022-06-28 | Bioverativ Therapeutics Inc. | Chimeric factor VIII polypeptides and uses thereof |
| CN111574632A (zh) | 2012-02-15 | 2020-08-25 | 比奥贝拉蒂治疗公司 | 因子viii组合物及其制备和使用方法 |
| EP3549953A1 (en) | 2012-02-15 | 2019-10-09 | Bioverativ Therapeutics Inc. | Recombinant factor viii proteins |
| EP2666782A1 (en) * | 2012-05-22 | 2013-11-27 | Imnate Sarl | Coagulation factor VIII with reduced immunogenicity. |
| AU2013270683A1 (en) | 2012-06-08 | 2014-12-11 | Biogen Ma Inc. | Chimeric clotting factors |
| EP3693000B1 (en) | 2012-06-08 | 2022-03-02 | Bioverativ Therapeutics Inc. | Procoagulant compounds |
| WO2014008480A2 (en) | 2012-07-06 | 2014-01-09 | Biogen Idec Ma Inc. | Cell line expressing single chain factor viii polypeptides and uses thereof |
| CA2878679A1 (en) | 2012-07-11 | 2014-01-16 | Amunix Operating Inc. | Factor viii complex with xten and von willebrand factor protein, and uses thereof |
| HK1212882A1 (zh) | 2012-07-25 | 2016-06-24 | Bioverativ Therapeutics Inc. | 血液因子的監測分析及其用途 |
| US10391152B2 (en) | 2012-10-18 | 2019-08-27 | Bioverativ Therapeutics Inc. | Methods of using a fixed dose of a clotting factor |
| EP2914293A4 (en) | 2012-10-30 | 2016-04-20 | Biogen Ma Inc | METHOD OF USE OF FVIII POLYPEPTIDE |
| US10272163B2 (en) | 2012-12-07 | 2019-04-30 | The Regents Of The University Of California | Factor VIII mutation repair and tolerance induction |
| EP4223772A3 (en) | 2013-02-15 | 2023-10-18 | Bioverativ Therapeutics Inc. | Optimized factor viii gene |
| WO2014144549A1 (en) | 2013-03-15 | 2014-09-18 | Biogen Idec Ma Inc. | Factor ix polypeptide formulations |
| TWI629993B (zh) | 2013-03-15 | 2018-07-21 | 美商生物化學醫療公司 | 因子ｖｉｉｉ多肽調配物 |
| EP4368194A3 (en) | 2013-06-28 | 2024-07-31 | Bioverativ Therapeutics Inc. | Thrombin cleavable linker with xten and its uses thereof |
| EP3875106A1 (en) | 2013-08-08 | 2021-09-08 | Bioverativ Therapeutics Inc. | Purification of chimeric fviii molecules |
| EP3033097B1 (en) | 2013-08-14 | 2021-03-10 | Bioverativ Therapeutics Inc. | Factor viii-xten fusions and uses thereof |
| CN105848670A (zh) | 2013-10-22 | 2016-08-10 | Dbv技术公司 | 通过诱导对血液因子的耐受治疗血友病的方法 |
| WO2015070014A1 (en) | 2013-11-08 | 2015-05-14 | Biogen Idec Ma Inc. | Procoagulant fusion compound |
| WO2015085276A1 (en) | 2013-12-06 | 2015-06-11 | Biogen Idec Ma Inc. | Population pharmacokinetics tools and uses thereof |
| EP2881463A1 (en) | 2013-12-09 | 2015-06-10 | DRK-Blutspendedienst Baden-Württemberg-Hessen gGmbH | Factor IX variants with clotting activity in absence of their cofactor and/or with increased F.IX clotting activity and their use for treating bleeding disorders |
| SI3091997T1 (sl) | 2014-01-10 | 2022-10-28 | Bioverativ Therapeutics Inc. | Himerni proteini faktorja VIII in njihova uporaba |
| NZ722391A (en) | 2014-02-04 | 2022-12-23 | Biogen Ma Inc | Use of cation-exchange chromatography in the flow-through mode to enrich post-translational modifications |
| EP3107561A4 (en) * | 2014-02-19 | 2017-12-20 | Bloodworks | Factor viii b cell epitope variants having reduced immunogenicity |
| EP3114138B1 (en) | 2014-03-05 | 2021-11-17 | Pfizer Inc. | Improved muteins of clotting factor viii |
| US11008561B2 (en) | 2014-06-30 | 2021-05-18 | Bioverativ Therapeutics Inc. | Optimized factor IX gene |
| MA40864A (fr) | 2014-10-31 | 2017-09-05 | Biogen Ma Inc | Hypotaurine, gaba, bêta-alanine et choline pour la régulation de l'accumulation de sous-produits résiduaires dans des procédés de culture de cellules mammifères |
| BR112018002150A2 (pt) | 2015-08-03 | 2018-09-18 | Bioverativ Therapeutics Inc | proteínas de fusão do fator ix e métodos de fabricação e uso das mesmas |
| PE20231949A1 (es) * | 2015-10-30 | 2023-12-05 | Spark Therapeutics Inc | VARIANTES DEL FACTOR VIII REDUCIDO CON CpG, COMPOSICIONES Y METODOS Y USOS PARA EL TRATAMIENTO DE TRASTORNOS DE LA HEMOSTASIA |
| SG10202106307UA (en) | 2015-11-13 | 2021-07-29 | Takeda Pharmaceuticals Co | Viral vectors encoding recombinant fviii variants with increased expression for gene therapy of hemophilia a |
| EA202092049A1 (ru) | 2015-11-13 | 2020-11-10 | Баксалта Инкорпорейтед | Вирусные векторы, кодирующие рекомбинантные варианты fviii с повышенной экспрессией для генной терапии гемофилии a |
| SG11201806398YA (en) | 2016-02-01 | 2018-08-30 | Bioverativ Therapeutics Inc | Optimized factor viii genes |
| KR102175878B1 (ko) | 2016-06-24 | 2020-11-06 | 재단법인 목암생명과학연구소 | Fviii 및 vwf 인자를 포함하는 키메라 단백질 및 그 용도 |
| AU2017366709A1 (en) | 2016-12-02 | 2019-07-18 | Bioverativ Therapeutics Inc. | Methods of treating hemophilic arthropathy using chimeric clotting factors |
| KR20190091292A (ko) | 2016-12-02 | 2019-08-05 | 바이오버라티브 테라퓨틱스 인크. | 응고 인자에 대한 면역 내성 유도 방법 |
| US11633504B2 (en) | 2017-05-09 | 2023-04-25 | Emory University | Nucleic acids encoding clotting factor variants and their use |
| BR112020002394A2 (pt) | 2017-08-09 | 2020-07-28 | Bioverativ Therapeutics Inc. | moléculas de ácidos nucleicos e usos das mesmas |
| US20210038744A1 (en) | 2018-02-01 | 2021-02-11 | Bioverativ Therapeutics Inc. | Use of lentiviral vectors expressing factor viii |
| CA3096038A1 (en) | 2018-04-04 | 2019-10-10 | Sigilon Therapeutics, Inc. | Implantable particles and related methods |
| SG11202010767SA (en) | 2018-05-18 | 2020-11-27 | Bioverativ Therapeutics Inc | Methods of treating hemophilia a |
| KR20210034013A (ko) | 2018-07-16 | 2021-03-29 | 박스알타 인코퍼레이티드 | 발현이 증가된 재조합 fviii 변이체들을 인코딩하는 바이러스 벡터를 이용한 혈우병의 유전적 치료법 |
| EP3833766A1 (en) | 2018-08-09 | 2021-06-16 | Bioverativ Therapeutics Inc. | Nucleic acid molecules and uses thereof for non-viral gene therapy |
| UY38389A (es) | 2018-09-27 | 2020-04-30 | Sigilon Therapeutics Inc | Dispositivos implantables para terapia celular y métodos relacionados |
| TWI851647B (zh) | 2019-01-16 | 2024-08-11 | 日商武田藥品工業股份有限公司 | 用於a型血友病基因治療之編碼表現增加之重組fviii變異體的病毒載體 |
| CA3144630A1 (en) | 2019-06-19 | 2020-12-24 | Bioverativ Therapeutics Inc. | Methods and compositions for treating hemophilia and low bone mineral density with factor viiifc protein |
| EP3986481A2 (en) | 2019-06-20 | 2022-04-27 | Takeda Pharmaceutical Company Limited | Method of treatment with viral-based gene therapy |
| CA3152600A1 (en) | 2019-09-30 | 2021-04-08 | Andrew KROETSCH | Lentiviral vector formulations |
| US20230023826A1 (en) | 2019-12-12 | 2023-01-26 | Takeda Pharmaceutical Company Limited | Gene therapy of hemophilia a using viral vectors encoding recombinant fviii variants with increased expression |
| IL299333A (en) | 2020-06-24 | 2023-02-01 | Bioverativ Therapeutics Inc | Methods for the purification of viral vectors |
| TW202246505A (zh) * | 2021-03-05 | 2022-12-01 | 俄羅斯聯邦商亞那拜恩有限公司 | 編碼凝血因子ｉｘ蛋白的密碼子優化的核酸及其用途 |
| CN117098996A (zh) * | 2021-03-31 | 2023-11-21 | 美国血液技术公司 | 止血测量装置质量控制制剂 |
| US20240269241A1 (en) | 2021-06-14 | 2024-08-15 | Takeda Pharmaceutical Company Limited | Gene therapy of hemophilia a using viral vectors encoding recombinant fviii variants with increased expression |
| US20230084036A1 (en) | 2021-08-23 | 2023-03-16 | Bioverativ Therapeutics Inc. | Optimized factor viii genes |
| AU2022355088A1 (en) | 2021-09-30 | 2024-05-16 | Bioverativ Therapeutics Inc. | Nucleic acids encoding factor viii polypeptides with reduced immunogenicity |
| JP2025534659A (ja) | 2022-10-11 | 2025-10-17 | シギロン セラピューティクス， インコーポレイテッド | 疾患治療のための改変細胞及び移植可能エレメント |
| WO2025008774A1 (en) | 2023-07-05 | 2025-01-09 | Takeda Pharmaceutical Company Limited | Viral vectors encoding recombinant fviii variants with increased expression for gene therapy of hemophilia a |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4757006A (en) | 1983-10-28 | 1988-07-12 | Genetics Institute, Inc. | Human factor VIII:C gene and recombinant methods for production |
| EP0182448A3 (en) | 1984-08-24 | 1987-10-28 | Genetics Institute, Inc. | Production of factor viii and related products |
| AU5772886A (en) | 1985-04-12 | 1986-11-05 | Genetics Institute Inc. | Novel procoagulant proteins |
| JPH0387173A (ja) | 1987-09-10 | 1991-04-11 | Teijin Ltd | ヒト活性化天然型ファクター８ｃの製造方法及びそれに用いる形質転換体 |
| DK162233C (da) | 1989-11-09 | 1992-03-16 | Novo Nordisk As | Fremgangsmaade til isolering af faktor viii fra blodplasma og pharmaceutisk praeparat indeholdende den saaledes isolerede fator viii |
| WO1991008216A1 (en) * | 1989-12-01 | 1991-06-13 | Genpharm International, Inc. | Production of recombinant polypeptides by bovine species and transgenic methods |
| US5663060A (en) | 1992-04-07 | 1997-09-02 | Emory University | Hybrid human/animal factor VIII |
| US6180371B1 (en) * | 1996-06-26 | 2001-01-30 | Emory University | Modified factor VIII |
| US5364771A (en) | 1992-04-07 | 1994-11-15 | Emory University | Hybrid human/porcine factor VIII |
| US5563045A (en) | 1992-11-13 | 1996-10-08 | Genetics Institute, Inc. | Chimeric procoagulant proteins |
| WO1997003193A1 (en) | 1995-07-11 | 1997-01-30 | Chiron Corporation | Novel factor viii:c polypeptide analogs with altered metal-binding properties |
| WO1997003191A1 (en) | 1995-07-11 | 1997-01-30 | Chiron Corporation | Novel factor viii:c polypeptide analogs comprising factor v domains or subdomains |
| CN1205221C (zh) * | 2000-09-19 | 2005-06-08 | 埃默里大学 | 修饰的凝血因子ⅷ |
| WO2003047507A2 (en) * | 2001-11-30 | 2003-06-12 | Emory University | Factor viii c2 domain variants |
| US7105745B2 (en) * | 2002-12-31 | 2006-09-12 | Thomas & Betts International, Inc. | Water resistant electrical floor box cover assembly |
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