KR102484553B1 - A형 혈우병의 유전자 요법을 위한 증가된 발현을 갖는 재조합 fviii 변이체를 인코딩하는 바이러스 벡터 - Google Patents

A형 혈우병의 유전자 요법을 위한 증가된 발현을 갖는 재조합 fviii 변이체를 인코딩하는 바이러스 벡터 Download PDF

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KR102484553B1
KR102484553B1 KR1020187015189A KR20187015189A KR102484553B1 KR 102484553 B1 KR102484553 B1 KR 102484553B1 KR 1020187015189 A KR1020187015189 A KR 1020187015189A KR 20187015189 A KR20187015189 A KR 20187015189A KR 102484553 B1 KR102484553 B1 KR 102484553B1
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factor viii
polynucleotide
sequence
nucleotide sequence
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팔코-귄터 팔크너
프란치스카 호링
조하네스 렝글러
한스페터 로텐스타이너
프리드리히 샤이프링거
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다케다 야쿠힌 고교 가부시키가이샤
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KR1020187015189A 2015-11-13 2016-11-11 A형 혈우병의 유전자 요법을 위한 증가된 발현을 갖는 재조합 fviii 변이체를 인코딩하는 바이러스 벡터 Active KR102484553B1 (ko)

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KR1020227046419A KR20230008256A (ko) 2015-11-13 2016-11-11 A형 혈우병의 유전자 요법을 위한 증가된 발현을 갖는 재조합 fviii 변이체를 인코딩하는 바이러스 벡터

Applications Claiming Priority (3)

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US201562255317P 2015-11-13 2015-11-13
US62/255,317 2015-11-13
PCT/US2016/061684 WO2017083762A1 (en) 2015-11-13 2016-11-11 Viral vectors encoding recombinant fviii variants with increased expression for gene therapy of hemophilia a

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KR102484553B1 true KR102484553B1 (ko) 2023-01-04

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KR1020227046419A Ceased KR20230008256A (ko) 2015-11-13 2016-11-11 A형 혈우병의 유전자 요법을 위한 증가된 발현을 갖는 재조합 fviii 변이체를 인코딩하는 바이러스 벡터

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US (4) US10189888B2 (https=)
EP (1) EP3374387A1 (https=)
JP (4) JP6768798B2 (https=)
KR (2) KR102484553B1 (https=)
CN (3) CN116479001A (https=)
AU (4) AU2016353353B2 (https=)
BR (1) BR112018009717B1 (https=)
CA (1) CA3005334A1 (https=)
CL (1) CL2018001299A1 (https=)
CO (1) CO2018005377A2 (https=)
EA (2) EA202190827A1 (https=)
IL (3) IL281038B2 (https=)
MX (1) MX2018005982A (https=)
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Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MY189674A (en) 2015-10-28 2022-02-24 Sangamo Therapeutics Inc Liver-specific constructs, factor viii expression cassettes and methods of use thereof
CA3005565A1 (en) * 2015-11-13 2017-05-18 Baxalta Incorporated Viral vectors encoding recombinant fviii variants with increased expression for gene therapy of hemophilia 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
US11191847B2 (en) 2016-04-15 2021-12-07 The Trustees Of The University Of Pennsylvania Gene therapy for treating hemophilia B
MX2018012537A (es) * 2016-04-15 2019-02-25 Univ Pennsylvania Terapia de genes para tratar hemofilia a.
BR112019009113A2 (pt) 2016-11-04 2019-07-16 Baxalta Incorporated formulações de vírus adenoassociado
EP3687580A1 (en) * 2017-09-27 2020-08-05 Sigilon Therapeutics, Inc. Methods, compositions, and implantable elements comprising active cells
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
US12091675B2 (en) * 2018-07-16 2024-09-17 Takeda Pharmaceutical Company Limited Gene therapy of hemophilia a using viral vectors encoding recombinant FVIII variants with increased expression
US12497632B2 (en) * 2018-08-03 2025-12-16 Sangamo Therapeutics, Inc. Clinical parameters by expression of factor VIII
GB201813528D0 (en) 2018-08-20 2018-10-03 Ucl Business Plc Factor IX encoding nucleotides
US10842885B2 (en) 2018-08-20 2020-11-24 Ucl Business Ltd 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
SG11202108357PA (en) 2019-02-15 2021-08-30 Crispr Therapeutics Ag 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
CN114375205A (zh) * 2019-06-20 2022-04-19 武田药品工业株式会社 用基于病毒的基因疗法进行治疗的方法
CN114929735A (zh) * 2019-11-01 2022-08-19 自由行疗法有限公司 因子viii构建体
WO2021119357A2 (en) * 2019-12-12 2021-06-17 Baxalta Incorporated Gene therapy of hemophilia a using viral vectors encoding recombinant fviii variants with increased expression
KR102817222B1 (ko) * 2021-04-02 2025-06-11 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
EP4211153A4 (en) * 2021-11-25 2023-11-01 Sichuan Real&Best Biotech Co., Ltd. ENGINEERED HUMAN FVII1 WITH INCREASED SECRETION ABILITY AND COAGULATION ACTIVITY
KR20250007615A (ko) * 2022-04-28 2025-01-14 조인트 스탁 컴퍼니 "바이오케드" Fviii-bdd를 인코딩하는 코돈 최적화된 핵산
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
WO2025180508A1 (en) * 2024-02-29 2025-09-04 Shanghai Vitalgen Biopharma Co., Ltd. Human factor viii variant expression cassettes and uses thereof for treating hemophilia a

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130017997A1 (en) 2010-08-19 2013-01-17 Amunix Operating Inc. Factor VIII Compositions and Methods of Making and Using Same
US20150071883A1 (en) 2013-09-12 2015-03-12 Biomarin Pharmaceutical Inc. Adeno-Associated Virus Factor VIII Vectors

Family Cites Families (52)

* Cited by examiner, † Cited by third party
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
ES8801674A1 (es) 1985-04-12 1988-02-16 Genetics Inst Un procedimiento para la preparacion de una proteina que presenta actividad procoagulante.
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
IL86693A (en) 1987-06-12 1994-06-24 Stichting Centraal Lab 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
EP0710288B1 (en) 1993-06-10 2006-04-05 Genetic Therapy, Inc. 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
US6200560B1 (en) 1998-10-20 2001-03-13 Avigen, Inc. Adeno-associated virus vectors for expression of factor VIII by target cells
US6221349B1 (en) * 1998-10-20 2001-04-24 Avigen, Inc. Adeno-associated 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
ES2319745T3 (es) 2001-10-05 2009-05-12 Expression Therapeutics, Llc Secuencias de acidos nucleicos y aminoacidos que codifican polipeptidos de factor viii de alto nivel de expresion, y metodos de uso.
PT1453547T (pt) 2001-12-17 2016-12-28 Univ Pennsylvania Sequências do vírus adeno-associado (aav) do serotipo 8, vetores contendo as mesmas, e utilizações destas
US7041635B2 (en) 2003-01-28 2006-05-09 In2Gen Co., Ltd. Factor VIII polypeptide
WO2005017149A1 (en) * 2003-06-03 2005-02-24 Cell Genesys, 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
ES2535877T3 (es) 2006-06-19 2015-05-18 Asklepios Biopharmaceutical, Inc. Genes de Factor VIII y Factor IX modificados y vectores para la terapia génica
CA2673459C (en) 2006-12-22 2016-09-13 Stefan Schulte Modified coagulation factors with prolonged in vivo half-life
KR100959454B1 (ko) 2007-12-10 2010-05-25 주식회사 동부하이텍 반도체 소자 및 그 제조 방법
CA2722238C (en) 2008-04-22 2017-11-28 Life Sciences Research Partners Vzw Liver-specific nucleic acid regulatory elements and methods and use thereof
ES2427627T3 (es) 2009-04-06 2013-10-31 Novo Nordisk A/S Entrega dirigida de proteínas de Factor VIII a plaquetas
GB0911870D0 (en) 2009-07-08 2009-08-19 Ucl Business Plc Optimised coding sequence and promoter
TW201217527A (en) 2010-07-09 2012-05-01 Biogen Idec Hemophilia Inc Processable single chain molecules and polypeptides made using same
WO2013016454A1 (en) 2011-07-25 2013-01-31 Biogen Idec Hemophilia Inc. Assays to monitor bleeding disorders
CN104271150A (zh) 2012-01-12 2015-01-07 比奥根艾迪克Ma公司 嵌合因子viii多肽及其用途
EA038705B1 (ru) 2012-01-12 2021-10-07 Биовератив Терапьютикс Инк. Способы снижения иммуногенности фактора свёртывания крови viii у пациентов, получающих лечение фактором viii
JP6256882B2 (ja) * 2012-02-15 2018-01-10 アムニクス オペレーティング インコーポレイテッド 第ｖｉｉｉ因子組成物、ならびに組成物の作製方法および用途
MX367100B (es) 2012-02-17 2019-08-05 The Children´S Hospital Of Philadelphia Composiciones del vector aav y metodos para su transferencia genetica a celulas, organos y tejidos.
CN104411338A (zh) 2012-04-02 2015-03-11 现代治疗公司 用于产生与人类疾病相关的生物制剂和蛋白质的修饰多核苷酸
GB201210357D0 (en) 2012-06-12 2012-07-25 Ucl Business Plc Factor VIII sequences
US8986991B2 (en) 2012-07-03 2015-03-24 Expression Therapeutics, Llc High yield suspension cell line, system and method for making same
AU2013336601B2 (en) 2012-10-26 2018-01-25 Vrije Universiteit Brussel Vector for liver-directed gene therapy of hemophilia and methods and use thereof
US10398787B2 (en) 2012-10-26 2019-09-03 Vrije Universiteit Brussel Vectors for liver-directed gene therapy of hemophilia and methods and use thereof
WO2014127215A1 (en) 2013-02-15 2014-08-21 Biogen Idec Ma Inc. Optimized factor viii gene
SG10201803999UA (en) 2013-03-15 2018-06-28 Bayer Healthcare Llc Recombinant factor viii formulations
LT3013855T (lt) * 2013-06-24 2021-01-25 Xiao, Weidong Mutavusio viii faktoriaus kompozicijos ir metodai
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
MX388739B (es) * 2015-02-06 2025-03-20 Univ North Carolina Chapel Hill Casetes optimizados de expresión del gen humano del factor viii de coagulación y su uso.
US11007280B2 (en) 2015-03-17 2021-05-18 Vrije Universiteit Brussel Optimized liver-specific expression systems for FVIII and 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

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130017997A1 (en) 2010-08-19 2013-01-17 Amunix Operating Inc. Factor VIII Compositions and Methods of Making and Using Same
US20150071883A1 (en) 2013-09-12 2015-03-12 Biomarin Pharmaceutical Inc. Adeno-Associated Virus Factor VIII Vectors

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