TWI753168B - 用於血友病b基因療法之編碼具有增強表現的重組fix變異體之病毒載體 - Google Patents

用於血友病b基因療法之編碼具有增強表現的重組fix變異體之病毒載體 Download PDF

Info

Publication number
TWI753168B
TWI753168B TW107117388A TW107117388A TWI753168B TW I753168 B TWI753168 B TW I753168B TW 107117388 A TW107117388 A TW 107117388A TW 107117388 A TW107117388 A TW 107117388A TW I753168 B TWI753168 B TW I753168B
Authority
TW
Taiwan
Prior art keywords
seq
factor
sequence
polynucleotide
nucleic acid
Prior art date
Application number
TW107117388A
Other languages
English (en)
Chinese (zh)
Other versions
TW201900184A (zh
Inventor
法郎西斯卡 侯恩林
約翰尼斯 朗格勒
佛可 岡特 佛卡納
翰斯彼得 羅特斯登能
費德瑞奇 雪佛玲格
Original Assignee
日商武田藥品工業股份有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 日商武田藥品工業股份有限公司 filed Critical 日商武田藥品工業股份有限公司
Publication of TW201900184A publication Critical patent/TW201900184A/zh
Application granted granted Critical
Publication of TWI753168B publication Critical patent/TWI753168B/zh

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424Serine endopeptidases (3.4.21)
    • C12N9/644Coagulation factor IXa (3.4.21.22)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088Compounds having three or more nucleosides or nucleotides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66Microorganisms or materials therefrom
    • A61K35/76Viruses; Subviral particles; Bacteriophages
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46Hydrolases (3)
    • A61K38/48Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/482Serine endopeptidases (3.4.21)
    • A61K38/4846Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/005Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
    • A61K48/0058Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/005Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
    • A61K48/0066Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/745Blood coagulation or fibrinolysis factors
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62DNA sequences coding for fusion proteins
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86Viral vectors
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y304/00Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21Serine endopeptidases (3.4.21)
    • C12Y304/21022Coagulation factor IXa (3.4.21.22)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2750/00MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011Details
    • C12N2750/14011Parvoviridae
    • C12N2750/14111Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141Use of virus, viral particle or viral elements as a vector
    • C12N2750/14143Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2800/00Nucleic acids vectors
    • C12N2800/10Plasmid DNA
    • C12N2800/106Plasmid DNA for vertebrates
    • C12N2800/107Plasmid DNA for vertebrates for mammalian
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2800/00Nucleic acids vectors
    • C12N2800/22Vectors comprising a coding region that has been codon optimised for expression in a respective host
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2830/00Vector systems having a special element relevant for transcription
    • C12N2830/008Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2830/00Vector systems having a special element relevant for transcription
    • C12N2830/42Vector systems having a special element relevant for transcription being an intron or intervening sequence for splicing and/or stability of RNA

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Plant Pathology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physics & Mathematics (AREA)
  • Virology (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Diabetes (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Immunology (AREA)
  • Toxicology (AREA)
  • Mycology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
TW107117388A 2017-05-22 2018-05-22 用於血友病b基因療法之編碼具有增強表現的重組fix變異體之病毒載體 TWI753168B (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201762509616P 2017-05-22 2017-05-22
US62/509,616 2017-05-22

Publications (2)

Publication Number Publication Date
TW201900184A TW201900184A (zh) 2019-01-01
TWI753168B true TWI753168B (zh) 2022-01-21

Family

ID=62621009

Family Applications (1)

Application Number Title Priority Date Filing Date
TW107117388A TWI753168B (zh) 2017-05-22 2018-05-22 用於血友病b基因療法之編碼具有增強表現的重組fix變異體之病毒載體

Country Status (17)

Country Link
US (2) US10842853B2 (https=)
EP (1) EP3630974A1 (https=)
JP (1) JP6961171B2 (https=)
KR (2) KR102386890B1 (https=)
CN (2) CN110945127B (https=)
AR (1) AR112057A1 (https=)
AU (1) AU2018272831B2 (https=)
BR (1) BR112019024256A2 (https=)
CA (1) CA3064730A1 (https=)
CL (2) CL2019003395A1 (https=)
CO (1) CO2019012885A2 (https=)
IL (2) IL280637B2 (https=)
MX (2) MX2019013836A (https=)
NZ (1) NZ759034A (https=)
TW (1) TWI753168B (https=)
WO (1) WO2018217731A1 (https=)
ZA (1) ZA201907716B (https=)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201420139D0 (en) 2014-11-12 2014-12-24 Ucl Business Plc Factor IX gene therapy
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
AU2019360270B2 (en) 2018-10-18 2025-08-07 Intellia Therapeutics, Inc. Compositions and methods for expressing factor IX.
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
US11596671B2 (en) * 2019-02-01 2023-03-07 Takeda Pharmaceutical Company Limited Gene therapy of hemophilia B using viral vectors encoding recombinant fix variants with increased expression
AU2020242945B2 (en) * 2019-03-19 2025-06-26 CSL Innovation Pty Ltd Factor IX variants and uses thereof in therapy
CN114207135A (zh) * 2019-06-11 2022-03-18 夏尔人类遗传性治疗公司 用于治疗由失调的血浆激肽释放酶介导的疾病的抗体的腺相关病毒载体递送
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
CN110684798A (zh) * 2019-09-03 2020-01-14 深圳新诺微环生物科技有限公司 肌肉靶向的微环dna基因治疗
EP4087489B1 (en) * 2020-01-08 2025-05-14 Vitruvia Holdings Inc. Methods and computing system for processing ultrasound image to determine health of subdermal tissue
JP2023510392A (ja) * 2020-01-16 2023-03-13 武田薬品工業株式会社 フェニルケトン尿症に対するアデノ随伴ウイルスベースの遺伝子治療
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
JP2024521537A (ja) * 2021-06-23 2024-05-31 フロンテーラ セラピューティクス,インク. 血友病bを処置するための組成物および方法
CN114277057B (zh) * 2021-07-09 2023-10-13 上海天泽云泰生物医药有限公司 用于治疗或预防b型血友病的重组腺相关病毒载体和方法
US20230149563A1 (en) * 2021-10-27 2023-05-18 Regeneron Pharmaceuticals, Inc. Compositions and methods for expressing factor ix for hemophilia b therapy
CN118460618A (zh) * 2022-04-19 2024-08-09 康霖生物科技(杭州)有限公司 一种用于遗传性凝血因子缺乏病治疗的核酸构建体
WO2025143742A1 (ko) * 2023-12-26 2025-07-03 삼성바이오에피스 주식회사 혈액응고인자 IX를 암호화하는 코돈-최적화된 폴리뉴클레오티드 및 이를 포함하는 rAAV 생산용 플라스미드

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2438931B1 (en) * 2004-09-22 2013-11-13 St. Jude Children's Research Hospital Improved expression of factor IX in gene therapy vectors

Family Cites Families (31)

* 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
US5139941A (en) 1985-10-31 1992-08-18 University Of Florida Research Foundation, Inc. AAV transduction vectors
US6268213B1 (en) 1992-06-03 2001-07-31 Richard Jude Samulski Adeno-associated virus vector and cis-acting regulatory and promoter elements capable of expressing at least one gene and method of using same for gene therapy
EP0710288B1 (en) 1993-06-10 2006-04-05 Genetic Therapy, Inc. Adenoviral vectors for treatment of hemophilia
US5786464C1 (en) 1994-09-19 2012-04-24 Gen Hospital Corp Overexpression of mammalian and viral proteins
JPH10506530A (ja) 1994-09-23 1998-06-30 ザ ジェネラル ホスピタル コーポレーション 哺乳類細胞において外来遺伝子を発現する非哺乳類dnaウイルスの使用
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
US5858351A (en) 1996-01-18 1999-01-12 Avigen, Inc. Methods for delivering DNA to muscle cells using recombinant adeno-associated virus vectors
US5866552A (en) 1996-09-06 1999-02-02 The Trustees Of The University Of Pennsylvania Method for expressing a gene in the absence of an immune response
US6114148C1 (en) 1996-09-20 2012-05-01 Gen Hospital Corp High level expression of proteins
EP1005376B1 (en) 1997-03-14 2010-11-03 The Children's Hospital of Philadelphia Compositions for use in gene therapy for treatment of hemophilia
US6531298B2 (en) 1997-07-21 2003-03-11 The University Of North Carolina At Chapel Hill Factor IX antihemophilic factor with increased clotting activity
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
WO2000074688A1 (en) 1999-06-08 2000-12-14 The Children's Hospital Of Philadelphia Methods for preventing formation of inhibitory antibodies in the setting of gene therapy
CN1148228C (zh) 2000-08-30 2004-05-05 夏家辉 治疗血友病b的基因药物及其制备方法
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
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
EP2423307A1 (en) * 2006-06-19 2012-02-29 Catalyst Biosciences, Inc. Modified coagulation factor IV polypeptides and use thereof for treatment
CA2722238C (en) 2008-04-22 2017-11-28 Life Sciences Research Partners Vzw Liver-specific nucleic acid regulatory elements and methods and use thereof
TR201813067T4 (tr) 2008-09-15 2018-09-21 Uniqure Biopharma B V Faktör IX polipeptit mutantı, bunun kullanımları ve bunu üretmeye yönelik bir yöntem.
US9663778B2 (en) * 2009-07-09 2017-05-30 OPKO Biologies Ltd. Long-acting coagulation factors and methods of producing same
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
HK1202434A1 (en) 2011-11-22 2015-10-02 The Children's Hospital Of Philadelphia Virus vectors for highly efficient transgene delivery
CA3018046A1 (en) * 2011-12-16 2013-06-20 Moderna Therapeutics, Inc. Modified nucleoside, nucleotide, and nucleic acid compositions
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.
WO2014063753A1 (en) 2012-10-26 2014-05-01 Vrije Universiteit Brussel Hyper-active factor ix vectors for liver-directed gene therapy of hemophilia 'b' and methods and use thereof
AU2013336601B2 (en) * 2012-10-26 2018-01-25 Vrije Universiteit Brussel Vector for liver-directed gene therapy of hemophilia and methods and use thereof
US11007280B2 (en) 2015-03-17 2021-05-18 Vrije Universiteit Brussel Optimized liver-specific expression systems for FVIII and FIX
MX390848B (es) * 2015-06-23 2025-03-21 Childrens Hospital Philadelphia Factor ix modificado, y composiciones, metodos y usos para la transferencia de genes a celulas, organos y tejidos.
CN106497949A (zh) * 2016-10-14 2017-03-15 上海交通大学医学院附属瑞金医院 一种高活性凝血因子ix突变体、重组蛋白与融合蛋白的制备与应用

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2438931B1 (en) * 2004-09-22 2013-11-13 St. Jude Children's Research Hospital Improved expression of factor IX in gene therapy vectors

Also Published As

Publication number Publication date
MX2024009571A (es) 2024-08-14
BR112019024256A2 (pt) 2020-06-09
US10842853B2 (en) 2020-11-24
WO2018217731A1 (en) 2018-11-29
JP2020520662A (ja) 2020-07-16
US20210128700A1 (en) 2021-05-06
IL280637B1 (en) 2024-07-01
KR102551733B1 (ko) 2023-07-06
US20180339026A1 (en) 2018-11-29
IL280637A (en) 2021-03-25
TW201900184A (zh) 2019-01-01
CN118581121A (zh) 2024-09-03
CA3064730A1 (en) 2018-11-29
CN110945127A (zh) 2020-03-31
IL280637B2 (en) 2024-11-01
CO2019012885A2 (es) 2020-01-17
CN110945127B (zh) 2024-07-12
RU2019142702A3 (https=) 2021-10-12
AU2018272831B2 (en) 2024-12-12
CL2019003395A1 (es) 2020-04-17
NZ759034A (en) 2023-07-28
CL2020002445A1 (es) 2020-12-28
MX2019013836A (es) 2020-01-30
KR102386890B1 (ko) 2022-04-15
ZA201907716B (en) 2022-06-29
IL270567B (en) 2021-03-25
KR20200010443A (ko) 2020-01-30
AU2018272831A1 (en) 2019-11-28
RU2019142702A (ru) 2021-06-24
KR20220050238A (ko) 2022-04-22
JP6961171B2 (ja) 2021-11-05
EP3630974A1 (en) 2020-04-08
AR112057A1 (es) 2019-09-18

Similar Documents

Publication Publication Date Title
TWI753168B (zh) 用於血友病b基因療法之編碼具有增強表現的重組fix變異體之病毒載體
TWI777175B (zh) 用於a型血友病基因治療之編碼表現增加之重組fviii變異體之病毒載體
US20240100128A1 (en) Gene therapy of hemophilia b using viral vectors encoding recombinant fix variants with increased expression
TWI851647B (zh) 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
TWI823830B (zh) 用於a型血友病基因治療之編碼表現增加之重組fviii變異體之病毒載體
US20250043310A1 (en) Gene therapy of hemophilia a using viral vectors encoding recombinant fviii variants with increased expression
CN111108196A (zh) 凝血因子变体及其用途
US20230023826A1 (en) Gene therapy of hemophilia a using viral vectors encoding recombinant fviii variants with increased expression
RU2773956C2 (ru) Вирусные векторы, кодирующие рекомбинантные варианты fix с повышенной экспрессией, для генотерапии гемофилии в
EA047630B1 (ru) Вирусные векторы, кодирующие рекомбинантные варианты fviii с повышенной экспрессией для генной терапии гемофилии а