JP6768798B2 - 組換えｆｖｉｉｉ変異型をコードする血友病ａ遺伝子治療用高発現ウイルスベクター - Google Patents
組換えｆｖｉｉｉ変異型をコードする血友病ａ遺伝子治療用高発現ウイルスベクター Download PDFInfo
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| MX2018005969A (es) | 2015-11-13 | 2018-11-29 | Baxalta Inc | Vectores virales que codifican variantes del factor fviii recombinantes con mayor expresión para la terapia génica de hemofilia a. |
| EA202190827A1 (ru) | 2015-11-13 | 2021-11-30 | Баксалта Инкорпорейтед | Вирусные векторы, кодирующие рекомбинантные варианты fviii с повышенной экспрессией для генной терапии гемофилии a |
| WO2017180861A1 (en) | 2016-04-15 | 2017-10-19 | The Trustees Of The University Of Pennsulvania | Gene therapy for treating hemophilia b |
| KR102450833B1 (ko) * | 2016-04-15 | 2022-10-05 | 더 트러스티스 오브 더 유니버시티 오브 펜실베니아 | 혈우병 a 치료용 유전자 요법 |
| WO2018128689A1 (en) | 2016-11-04 | 2018-07-12 | Baxalta Incorporated | Adeno-associated virus formulations |
| WO2019067766A1 (en) * | 2017-09-27 | 2019-04-04 | Sigilon Therapeutics, Inc. | METHODS, COMPOSITIONS AND IMPLANTABLE ELEMENTS COMPRISING ACTIVE CELLS |
| US20200248179A1 (en) * | 2017-10-02 | 2020-08-06 | Research Institute At Nationwide Children's Hospital | MiRNA Detargeting System for Tissue Specific Interference |
| KR102105145B1 (ko) * | 2017-10-13 | 2020-05-13 | 영남대학교 산학협력단 | 촬영 장치 및 용기 |
| KR101952102B1 (ko) * | 2017-12-07 | 2019-02-26 | 주식회사 지앤피바이오사이언스 | 단백질 발현량이 증대된 인자 ⅷ 변이체 발현벡터 |
| KR20210034013A (ko) * | 2018-07-16 | 2021-03-29 | 박스알타 인코퍼레이티드 | 발현이 증가된 재조합 fviii 변이체들을 인코딩하는 바이러스 벡터를 이용한 혈우병의 유전적 치료법 |
| WO2020028830A1 (en) * | 2018-08-03 | 2020-02-06 | Sangamo Therapeutics, Inc. | Improved clinical parameters by expression of factor viii |
| US10842885B2 (en) | 2018-08-20 | 2020-11-24 | Ucl Business Ltd | Factor IX encoding nucleotides |
| GB201813528D0 (en) | 2018-08-20 | 2018-10-03 | Ucl Business Plc | Factor IX encoding nucleotides |
| 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 |
| AU2020221340A1 (en) | 2019-02-15 | 2021-09-16 | Bayer Healthcare Llc | Gene editing for hemophilia A with improved Factor VIII expression |
| BR112021015776A2 (pt) * | 2019-06-05 | 2021-11-09 | Bayer Healthcare Llc | Edição de gene para hemofilia a com expressão de fator viii melhorada |
| EP3986481A2 (en) * | 2019-06-20 | 2022-04-27 | Takeda Pharmaceutical Company Limited | Method of treatment with viral-based gene therapy |
| CN114901686A (zh) * | 2019-11-01 | 2022-08-12 | 自由行疗法有限公司 | 因子viii多肽 |
| EP4073106A2 (en) * | 2019-12-12 | 2022-10-19 | Takeda Pharmaceutical Company Limited | Gene therapy of hemophilia a using viral vectors encoding recombinant fviii variants with increased expression |
| WO2022211604A1 (ko) * | 2021-04-02 | 2022-10-06 | 연세대학교 산학협력단 | Fe-fviii 변이 유전자로 교정된 줄기세포, 이로부터 분화된 내피 세포 및 이를 포함하는 혈우병 예방 또는 치료용 약제학적 조성물 |
| KR102421131B1 (ko) * | 2021-05-28 | 2022-07-15 | 알엔에이진(주) | 세포내에서 장시간동안 존재할 수 있는 외부 도입 mRNA를 선별하는 방법 |
| JP2024544499A (ja) * | 2021-11-25 | 2024-12-03 | 四川至善唯新生物科技有限公司 | 遺伝子工学的改変により得られた、分泌能と凝固活性を向上させた組換えヒト第ｖｉｉｉ因子 |
| MA68586A1 (fr) * | 2022-04-28 | 2025-04-30 | Joint Stock Company "Biocad" | Acide nucléique à codons optimisés codant pour fviii-bdd |
| CN115948408A (zh) * | 2022-09-23 | 2023-04-11 | 上海信致医药科技有限公司 | 改进的人凝血因子viii基因表达盒及其应用 |
| WO2024191428A1 (en) | 2023-03-14 | 2024-09-19 | Sigilon Therapeutics, Inc. | Hydrogel capsules comprising covalently photocrosslinked polysaccharides and islet cells |
| 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 (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4797368A (en) | 1985-03-15 | 1989-01-10 | The United States Of America As Represented By The Department Of Health And Human Services | Adeno-associated virus as eukaryotic expression vector |
| JPH0788399B2 (ja) | 1985-04-12 | 1995-09-27 | ジェネティックス・インスチチュ−ト・インコ−ポレ−テッド | 新規プロコアギュラント蛋白質 |
| US5139941A (en) | 1985-10-31 | 1992-08-18 | University Of Florida Research Foundation, Inc. | AAV transduction vectors |
| US5595886A (en) | 1986-01-27 | 1997-01-21 | Chiron Corporation | Protein complexes having Factor VIII:C activity and production thereof |
| US5543502A (en) | 1986-06-24 | 1996-08-06 | Novo Nordisk A/S | Process for producing a coagulation active complex of factor VIII fragments |
| US6060447A (en) | 1987-05-19 | 2000-05-09 | Chiron Corporation | Protein complexes having Factor VIII:C activity and production thereof |
| US6346513B1 (en) | 1987-06-12 | 2002-02-12 | Baxter Trading Gmbh | Proteins with factor VIII activity: process for their preparation using genetically-engineered cells and pharmaceutical compositions containing them |
| US5171844A (en) | 1987-06-12 | 1992-12-15 | Gist-Brocades N.W. | Proteins with factor viii activity: process for their preparation using genetically-engineered cells and pharmaceutical compositions containing them |
| FR2619314B1 (fr) | 1987-08-11 | 1990-06-15 | Transgene Sa | Analogue du facteur viii, procede de preparation et composition pharmaceutique le contenant |
| CA2162497A1 (en) | 1993-06-10 | 1994-12-22 | Sheila Connelly | Adenoviral vectors for treatment of hemophilia |
| SE504074C2 (sv) | 1993-07-05 | 1996-11-04 | Pharmacia Ab | Proteinberedning för subkutan, intramuskulär eller intradermal administrering |
| US6818439B1 (en) | 1994-12-30 | 2004-11-16 | Chiron Corporation | Methods for administration of recombinant gene delivery vehicles for treatment of hemophilia and other disorders |
| US5952198A (en) * | 1995-05-04 | 1999-09-14 | Bayer Corporation | Production of recombinant Factor VIII in the presence of liposome-like substances of mixed composition |
| SE9503380D0 (sv) | 1995-09-29 | 1995-09-29 | Pharmacia Ab | Protein derivatives |
| US6013516A (en) | 1995-10-06 | 2000-01-11 | The Salk Institute For Biological Studies | Vector and method of use for nucleic acid delivery to non-dividing cells |
| US6458563B1 (en) | 1996-06-26 | 2002-10-01 | Emory University | Modified factor VIII |
| US6114148C1 (en) | 1996-09-20 | 2012-05-01 | Gen Hospital Corp | High level expression of proteins |
| US5994136A (en) | 1997-12-12 | 1999-11-30 | Cell Genesys, Inc. | Method and means for producing high titer, safe, recombinant lentivirus vectors |
| US6924365B1 (en) | 1998-09-29 | 2005-08-02 | Transkaryotic Therapies, Inc. | Optimized messenger RNA |
| US6221349B1 (en) * | 1998-10-20 | 2001-04-24 | Avigen, Inc. | Adeno-associated vectors for expression of factor VIII by target cells |
| US6200560B1 (en) | 1998-10-20 | 2001-03-13 | Avigen, Inc. | Adeno-associated virus vectors for expression of factor VIII by target cells |
| US20060099685A1 (en) | 1999-04-15 | 2006-05-11 | Yallop Christopher A | Recombinant expression of factor VIII in human cells |
| CN1179976C (zh) * | 2000-12-29 | 2004-12-15 | 中国科学院上海生物化学研究所 | 产生凝血因子ⅷ的生产方法和宿主细胞 |
| EP1572889B1 (en) | 2001-10-05 | 2008-12-17 | Expression Therapeutics, LLC | Nucleic acid and amino acid sequences encoding high-level expressor factor viii polypeptides and methods of use |
| JP4810062B2 (ja) | 2001-12-17 | 2011-11-09 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | アデノ随伴ウイルス（ａａｖ）血清型８の配列 |
| US7041635B2 (en) | 2003-01-28 | 2006-05-09 | In2Gen Co., Ltd. | Factor VIII polypeptide |
| US7709224B2 (en) * | 2003-06-03 | 2010-05-04 | Biosante Pharmaceuticals, Inc. | Compositions and methods for enhanced expression of recombinant polypeptides from a single vector using a peptide cleavage site |
| US7943374B2 (en) | 2005-08-21 | 2011-05-17 | Markus Hildinger | Super-size adeno-associated viral vector harboring a recombinant genome larger than 5.7 kb |
| EP2037892B1 (en) | 2006-06-19 | 2015-03-18 | Asklepios Biopharmaceutical, Inc. | Modified factor viii and factor ix genes and vectors for gene therapy |
| KR101542752B1 (ko) | 2006-12-22 | 2015-08-10 | 체에스엘 베링 게엠베하 | 연장된 생체내 반감기를 갖는 변형된 응고 인자 |
| KR100959454B1 (ko) | 2007-12-10 | 2010-05-25 | 주식회사 동부하이텍 | 반도체 소자 및 그 제조 방법 |
| JP5797551B2 (ja) | 2008-04-22 | 2015-10-21 | フエー・イー・ベー・フエー・ゼツト・ウエー | 肝特異的核酸調節要素ならびにその方法および用途 |
| EP2417155B1 (en) | 2009-04-06 | 2013-06-19 | Novo Nordisk A/S | Targeted delivery of factor viii proteins to platelets |
| GB0911870D0 (en) | 2009-07-08 | 2009-08-19 | Ucl Business Plc | Optimised coding sequence and promoter |
| AU2011274423B2 (en) | 2010-07-09 | 2016-02-11 | Bioverativ Therapeutics Inc. | Chimeric clotting factors |
| US20130017997A1 (en) | 2010-08-19 | 2013-01-17 | Amunix Operating Inc. | Factor VIII Compositions and Methods of Making and Using Same |
| US10656167B2 (en) | 2011-07-25 | 2020-05-19 | Bioverativ Therapeutics Inc. | Assays to monitor bleeding disorders |
| HUE041595T2 (hu) * | 2012-01-12 | 2019-05-28 | Bioverativ Therapeutics Inc | A VIII-as faktorral szembeni immunogenitás csökkentése a VIII-as faktorterápiát kapó egyéneknél |
| HRP20191920T1 (hr) | 2012-01-12 | 2020-01-10 | Bioverativ Therapeutics Inc. | Kimerni polipeptidi faktora viii i njihova uporaba |
| CN119192402A (zh) * | 2012-02-15 | 2024-12-27 | 比奥贝拉蒂治疗公司 | 因子viii组合物及其制备和使用方法 |
| CN104520428B (zh) | 2012-02-17 | 2018-09-21 | 费城儿童医院 | 将基因转移到细胞、器官和组织的aav载体组合物和方法 |
| HK1206612A1 (en) * | 2012-04-02 | 2016-01-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of secreted proteins |
| GB201210357D0 (en) * | 2012-06-12 | 2012-07-25 | Ucl Business Plc | Factor VIII sequences |
| WO2014008172A2 (en) | 2012-07-03 | 2014-01-09 | Expression Therapeutics, Llc | High yield suspension cell line, system and method for making same |
| JP6454643B2 (ja) | 2012-10-26 | 2019-01-16 | フリーイェ・ユニヴェルシテイト・ブリュッセルＶｒｉｊｅ Ｕｎｉｖｅｒｓｉｅｉｔ Ｂｒｕｓｓｅｌ | 血友病の肝臓指向性遺伝子治療のためのベクター並びにその方法及び使用 |
| EP3513802B1 (en) | 2012-10-26 | 2023-11-29 | Vrije Universiteit Brussel | Vector for liver-directed gene therapy of hemophilia and methods and use thereof |
| PL2956477T5 (pl) | 2013-02-15 | 2024-05-27 | Bioverativ Therapeutics Inc. | Zoptymalizowany gen czynnika viii |
| RU2015144076A (ru) | 2013-03-15 | 2017-04-24 | БАЙЕР ХелсКер ЛЛСи | Композиции рекомбинантного фактора viii |
| LT3013855T (lt) | 2013-06-24 | 2021-01-25 | Xiao, Weidong | Mutavusio viii faktoriaus kompozicijos ir metodai |
| CA3178379A1 (en) * | 2013-09-12 | 2015-03-19 | Biomarin Pharmaceutical Inc. | Adeno-associated virus factor viii vectors |
| CN107427557B (zh) | 2014-08-13 | 2022-01-04 | 费城儿童医院 | 用于包装和表达变体因子viii以治疗血友病的改良表达组件 |
| KR102554850B1 (ko) * | 2015-02-06 | 2023-07-13 | 더 유니버시티 오브 노쓰 캐롤라이나 엣 채플 힐 | 최적화된 인간 응고 인자 viii 유전자 발현 카세트 및 그의 용도 |
| ES2764453T3 (es) | 2015-03-17 | 2020-06-03 | Univ Brussel Vrije | Sistemas de expresión específica de hígado optimizados para FVIII y FIX |
| EA202190827A1 (ru) | 2015-11-13 | 2021-11-30 | Баксалта Инкорпорейтед | Вирусные векторы, кодирующие рекомбинантные варианты fviii с повышенной экспрессией для генной терапии гемофилии a |
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