ZA200402606B - Modified factor IX. - Google Patents
Modified factor IX. Download PDFInfo
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- ZA200402606B ZA200402606B ZA200402606A ZA200402606A ZA200402606B ZA 200402606 B ZA200402606 B ZA 200402606B ZA 200402606 A ZA200402606 A ZA 200402606A ZA 200402606 A ZA200402606 A ZA 200402606A ZA 200402606 B ZA200402606 B ZA 200402606B
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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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
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- 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)
-
- 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
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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
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- 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
-
- 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)
-
- 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)
-
- 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)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Wood Science & Technology (AREA)
- Hematology (AREA)
- Toxicology (AREA)
- Biophysics (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Biotechnology (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Microbiology (AREA)
- Diabetes (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01121154 | 2001-09-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200402606B true ZA200402606B (en) | 2004-12-14 |
Family
ID=8178534
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200402606A ZA200402606B (en) | 2001-09-04 | 2004-04-01 | Modified factor IX. |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20040254106A1 (zh) |
| EP (1) | EP1427820A2 (zh) |
| JP (1) | JP2005501547A (zh) |
| KR (1) | KR20040039328A (zh) |
| CN (1) | CN1547608A (zh) |
| BR (1) | BR0212035A (zh) |
| CA (1) | CA2457429A1 (zh) |
| HU (1) | HUP0401534A3 (zh) |
| MX (1) | MXPA04001982A (zh) |
| PL (1) | PL369065A1 (zh) |
| RU (1) | RU2004110239A (zh) |
| WO (1) | WO2003020764A2 (zh) |
| ZA (1) | ZA200402606B (zh) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2084274A2 (en) * | 2006-06-19 | 2009-08-05 | Nautilus Technology LLC | Modified coagulation factor ix polypeptides and use thereof for treatment |
| KR101399175B1 (ko) * | 2006-07-21 | 2014-06-19 | 푼다싸웅 지 앙빠루 아 뻬스끼자 두 에스따두 지 싸웅 파울루 - 에피아뻬에에씨뻬 | 항염증성 및 항알레르기성 시클릭 펩티드 |
| AU2008279550B2 (en) | 2007-06-21 | 2012-08-09 | Angelica Therapeutics, Inc. | Modified toxins |
| US20110154516A1 (en) * | 2007-10-15 | 2011-06-23 | Stafford Darrel W | Human factor ix variants with an extended half life |
| EP2268297A4 (en) | 2008-02-29 | 2011-11-16 | Angelica Therapeutics Inc | MODIFIED TOXINS |
| SG189790A1 (en) * | 2008-04-16 | 2013-05-31 | Bayer Healthcare Llc | Modified factor ix polypeptides and uses thereof |
| FI3581650T3 (fi) | 2008-09-15 | 2023-03-23 | Uniqure Biopharma B V | IX-tekijän polypeptidimutantti, sen käyttöjä ja menetelmä sen valmistamiseksi |
| EA037095B1 (ru) | 2010-07-09 | 2021-02-05 | Биовератив Терапьютикс Инк. | Способ лечения гемофилии в и эпизодов кровотечения |
| 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 |
| WO2012170969A2 (en) | 2011-06-10 | 2012-12-13 | Biogen Idec Ma Inc. | Pro-coagulant compounds and methods of use thereof |
| WO2013016454A1 (en) | 2011-07-25 | 2013-01-31 | Biogen Idec Hemophilia Inc. | Assays to monitor bleeding disorders |
| US10001495B2 (en) | 2012-07-25 | 2018-06-19 | Bioverativ Therapeutics Inc. | Blood factor monitoring assay and uses thereof |
| WO2014052490A1 (en) | 2012-09-25 | 2014-04-03 | Biogen Idec Ma Inc. | Methods of using fix polypeptides |
| US10391152B2 (en) | 2012-10-18 | 2019-08-27 | Bioverativ Therapeutics Inc. | Methods of using a fixed dose of a clotting factor |
| US10717965B2 (en) | 2013-01-10 | 2020-07-21 | Gloriana Therapeutics, Inc. | Mammalian cell culture-produced neublastin antibodies |
| HRP20231183T1 (hr) | 2013-02-15 | 2024-01-05 | Bioverativ Therapeutics Inc. | Optimizirani gen faktora viii |
| TWI683666B (zh) | 2013-03-15 | 2020-02-01 | 美商百歐維拉提夫治療公司 | 因子ｉｘ多肽調配物 |
| JP2016519651A (ja) | 2013-03-15 | 2016-07-07 | アンジェリカ セラピューティックス，インク． | 改質された毒素 |
| WO2015048330A2 (en) | 2013-09-25 | 2015-04-02 | Biogen Idec Ma Inc. | On-column viral inactivation methods |
| EP3065769A4 (en) | 2013-11-08 | 2017-05-31 | Biogen MA Inc. | Procoagulant fusion compound |
| WO2015085276A1 (en) | 2013-12-06 | 2015-06-11 | Biogen Idec Ma Inc. | Population pharmacokinetics tools and uses thereof |
| US20160289633A1 (en) | 2013-12-20 | 2016-10-06 | Biogen Ma Inc. | Use of Perfusion Seed Cultures to Improve Biopharmaceutical Fed-Batch Production Capacity and Product Quality |
| KR102385372B1 (ko) | 2014-03-24 | 2022-04-11 | 바이오버라티브 테라퓨틱스 인크. | 동결건조된 ix 인자 제형 |
| US11008561B2 (en) | 2014-06-30 | 2021-05-18 | Bioverativ Therapeutics Inc. | Optimized factor IX gene |
| GB201420139D0 (en) | 2014-11-12 | 2014-12-24 | Ucl Business Plc | Factor IX gene therapy |
| UA126016C2 (uk) | 2015-08-03 | 2022-08-03 | Біовератів Терапеутікс Інк. | Злитий білок фактора іх |
| EP3411478B1 (en) | 2016-02-01 | 2022-06-08 | Bioverativ Therapeutics Inc. | Optimized factor viii genes |
| EP3548066A1 (en) | 2016-12-02 | 2019-10-09 | Bioverativ Therapeutics Inc. | Methods of treating hemophilic arthropathy using chimeric clotting factors |
| KR20190112763A (ko) | 2017-01-31 | 2019-10-07 | 바이오버라티브 테라퓨틱스 인크. | 인자 ix 융합 단백질 및 이의 제조 및 사용 방법 |
| KR20200035130A (ko) | 2017-08-09 | 2020-04-01 | 바이오버라티브 테라퓨틱스 인크. | 핵산 분자 및 이의 용도 |
| WO2019067766A1 (en) | 2017-09-27 | 2019-04-04 | Sigilon Therapeutics, Inc. | METHODS, COMPOSITIONS AND IMPLANTABLE ELEMENTS COMPRISING ACTIVE CELLS |
| US11491212B1 (en) | 2017-09-27 | 2022-11-08 | Catalyst Biosciences, Inc. | Subcutaneous administration of modified factor IX polypeptides and treatment of hemophilia B |
| WO2019195056A1 (en) | 2018-04-04 | 2019-10-10 | Sigilon Therapeutics, Inc. | Methods, compositions, and implantable elements comprising stem cells |
| TW202014181A (zh) | 2018-04-04 | 2020-04-16 | 美商希吉隆醫療公司 | 可植入顆粒及相關方法 |
| TW202015723A (zh) | 2018-05-18 | 2020-05-01 | 美商百歐維拉提夫治療公司 | 治療ａ型血友病的方法 |
| MX2021001599A (es) | 2018-08-09 | 2021-07-02 | Bioverativ Therapeutics Inc | Moleculas de acido nucleico y sus usos para la terapia genica no viral. |
| US10842885B2 (en) | 2018-08-20 | 2020-11-24 | Ucl Business Ltd | Factor IX encoding nucleotides |
| UY38389A (es) | 2018-09-27 | 2020-04-30 | Sigilon Therapeutics Inc | Dispositivos implantables para terapia celular y métodos relacionados |
| WO2020086408A1 (en) | 2018-10-26 | 2020-04-30 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | A high-yield perfusion-based transient gene expression bioprocess |
| JP2022531095A (ja) | 2019-04-17 | 2022-07-06 | コディアック バイオサイエンシーズ， インコーポレイテッド | エキソソーム及びａａｖの組成物 |
| 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 |
| WO2024081309A1 (en) | 2022-10-11 | 2024-04-18 | Sigilon Therapeutics, Inc. | Engineered cells and implantable elements for treatment of disease |
| WO2024081310A1 (en) | 2022-10-11 | 2024-04-18 | Sigilon Therapeutics, Inc. | Engineered cells and implantable elements for treatment of disease |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6180371B1 (en) * | 1996-06-26 | 2001-01-30 | Emory University | Modified factor VIII |
| US5621039A (en) * | 1993-06-08 | 1997-04-15 | Hallahan; Terrence W. | Factor IX- polymeric conjugates |
| JP2002512624A (ja) * | 1997-05-21 | 2002-04-23 | バイオベーション リミテッド | 非免疫原性タンパク質の製造方法 |
| EP1051432B1 (en) * | 1998-12-08 | 2007-01-24 | Biovation Limited | Method for reducing immunogenicity of proteins |
-
2002
- 2002-08-30 PL PL02369065A patent/PL369065A1/xx unknown
- 2002-08-30 RU RU2004110239/04A patent/RU2004110239A/ru not_active Application Discontinuation
- 2002-08-30 WO PCT/EP2002/009717 patent/WO2003020764A2/en not_active Application Discontinuation
- 2002-08-30 KR KR10-2004-7003227A patent/KR20040039328A/ko not_active Application Discontinuation
- 2002-08-30 CA CA002457429A patent/CA2457429A1/en not_active Abandoned
- 2002-08-30 US US10/488,671 patent/US20040254106A1/en not_active Abandoned
- 2002-08-30 HU HU0401534A patent/HUP0401534A3/hu unknown
- 2002-08-30 JP JP2003525034A patent/JP2005501547A/ja not_active Withdrawn
- 2002-08-30 MX MXPA04001982A patent/MXPA04001982A/es not_active Application Discontinuation
- 2002-08-30 BR BR0212035-6A patent/BR0212035A/pt not_active Application Discontinuation
- 2002-08-30 CN CNA028167597A patent/CN1547608A/zh active Pending
- 2002-08-30 EP EP02767457A patent/EP1427820A2/en not_active Withdrawn
-
2004
- 2004-04-01 ZA ZA200402606A patent/ZA200402606B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20040039328A (ko) | 2004-05-10 |
| MXPA04001982A (es) | 2004-06-07 |
| CN1547608A (zh) | 2004-11-17 |
| US20040254106A1 (en) | 2004-12-16 |
| PL369065A1 (en) | 2005-04-18 |
| BR0212035A (pt) | 2004-08-03 |
| WO2003020764A2 (en) | 2003-03-13 |
| RU2004110239A (ru) | 2005-10-20 |
| CA2457429A1 (en) | 2003-03-13 |
| WO2003020764A3 (en) | 2003-11-20 |
| HUP0401534A3 (en) | 2006-01-30 |
| HUP0401534A2 (hu) | 2004-11-29 |
| JP2005501547A (ja) | 2005-01-20 |
| EP1427820A2 (en) | 2004-06-16 |
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