CN112334489A - 密码子优化的酸性α-葡萄糖苷酶表达盒及其使用方法 - Google Patents

密码子优化的酸性α-葡萄糖苷酶表达盒及其使用方法 Download PDF

Info

Publication number
CN112334489A
CN112334489A CN201980040391.0A CN201980040391A CN112334489A CN 112334489 A CN112334489 A CN 112334489A CN 201980040391 A CN201980040391 A CN 201980040391A CN 112334489 A CN112334489 A CN 112334489A
Authority
CN
China
Prior art keywords
nucleic acid
gaa
aav
sequence
cpg dinucleotides
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
CN201980040391.0A
Other languages
English (en)
Chinese (zh)
Inventor
泽维尔·安谷拉
肖恩·阿穆尔
杰梅·诺丁
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Spark Therapeutics Inc
Original Assignee
Spark Therapeutics Inc
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 Spark Therapeutics Inc filed Critical Spark Therapeutics Inc
Publication of CN112334489A publication Critical patent/CN112334489A/zh
Pending legal-status Critical Current

Links

Images

Classifications

    • 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)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C12N9/2405—Glucanases
    • C12N9/2408—Glucanases acting on alpha -1,4-glucosidic bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/005—Medicinal 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/0102—Alpha-glucosidase (3.2.1.20)
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/0306—Animal model for genetic diseases
    • 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
    • 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
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • 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
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14151—Methods of production or purification of viral material
    • C12N2750/14152—Methods of production or purification of viral material relating to complementing cells and packaging systems for producing virus or viral particles
    • 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
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/22—Vectors comprising a coding region that has been codon optimised for expression in a respective host
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/001—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/50—Vector systems having a special element relevant for transcription regulating RNA stability, not being an intron, e.g. poly A signal

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Microbiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Virology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Immunology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
CN201980040391.0A 2018-05-16 2019-05-15 密码子优化的酸性α-葡萄糖苷酶表达盒及其使用方法 Pending CN112334489A (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201862672419P 2018-05-16 2018-05-16
US62/672,419 2018-05-16
US201862734454P 2018-09-21 2018-09-21
US62/734,454 2018-09-21
PCT/US2019/032502 WO2019222411A1 (en) 2018-05-16 2019-05-15 Codon-optimized acid αlpha-glucosidase expression cassettes and methods of using same

Publications (1)

Publication Number Publication Date
CN112334489A true CN112334489A (zh) 2021-02-05

Family

ID=68540790

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201980040391.0A Pending CN112334489A (zh) 2018-05-16 2019-05-15 密码子优化的酸性α-葡萄糖苷酶表达盒及其使用方法

Country Status (17)

Country Link
US (2) US12084693B2 (enExample)
EP (1) EP3794043A4 (enExample)
JP (2) JP2021523718A (enExample)
KR (1) KR20210021310A (enExample)
CN (1) CN112334489A (enExample)
AU (1) AU2019268363A1 (enExample)
BR (1) BR112020023393A2 (enExample)
CA (1) CA3100213A1 (enExample)
CL (1) CL2020002973A1 (enExample)
CO (1) CO2020015707A2 (enExample)
MX (1) MX2020012332A (enExample)
MY (1) MY207355A (enExample)
PE (1) PE20210337A1 (enExample)
PH (1) PH12020551957A1 (enExample)
SG (1) SG11202011191WA (enExample)
TW (1) TW202016310A (enExample)
WO (1) WO2019222411A1 (enExample)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024188025A1 (zh) * 2023-03-14 2024-09-19 北京据德医药科技有限公司 一种重组酸性α-葡萄糖苷酶及其用途

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2018281280B2 (en) 2017-06-07 2024-12-19 Regeneron Pharmaceuticals, Inc. Compositions and methods for internalizing enzymes
CN112040985A (zh) 2018-02-07 2020-12-04 瑞泽恩制药公司 用于递送治疗性蛋白质的方法和组合物
EP3793591A1 (en) 2018-05-17 2021-03-24 Regeneron Pharmaceuticals, Inc. Anti-cd63 antibodies, conjugates, and uses thereof
US12018087B2 (en) 2018-08-02 2024-06-25 Dyne Therapeutics, Inc. Muscle-targeting complexes comprising an anti-transferrin receptor antibody linked to an oligonucleotide and methods of delivering oligonucleotide to a subject
CN113226352B (zh) 2018-08-24 2025-08-26 星火治疗有限公司 最优化启动子序列、无内含子的表达结构及使用方法
EP3996696A1 (en) * 2019-07-09 2022-05-18 Genethon Treatment of glycogen storage disease (gsd)
MX2022007399A (es) 2019-12-20 2022-09-19 Codexis Inc Variantes de alfa-glucosidasa ácida diseñadas.
PE20240915A1 (es) * 2021-01-14 2024-04-30 Spark Therapeutics Inc Composiciones y metodos para tratar la enfermedad de fabry
CA3229580A1 (en) * 2021-08-20 2023-02-23 Anna Nikolaevna STRELKOVA Method for producing modified adeno-associated virus capsid
WO2023028567A2 (en) * 2021-08-25 2023-03-02 Canbridge Pharmaceuticals, Inc. Aav particles comprising a liver-tropic capsid protein and acid alpha-glucosidase (gaa) and their use to treat pompe disease
EP4392569A4 (en) * 2021-08-25 2025-07-16 Canbridge Pharmaceuticals Inc AAV PARTICLES COMPRISING A LIVER-TROPIC CAPSID PROTEIN AND AN ALPHA-GALACTOSIDASE AND THEIR USE FOR TREATING FABRY DISEASE
IL314482A (en) * 2022-02-02 2024-09-01 Regeneron Pharma Anti-tfr:gaa and anti-cd63:gaa insertions for treatment of pompe disease
WO2024231820A1 (en) * 2023-05-05 2024-11-14 Takeda Pharmaceutical Company Limited Treatment of pompe disease
IL326018A (en) * 2023-07-28 2026-03-01 Regeneron Pharma Introduction of anti-TFR:GAA and anti-CD63:GAA for the treatment of Pompe disease

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
WO2015196179A1 (en) * 2014-06-20 2015-12-23 University Of Florida Research Foundation, Inc. Methods of packaging multiple adeno-associated virus vectors
CN105745322A (zh) * 2013-09-17 2016-07-06 易登尼有限公司 用于增加生物质糖化的改良的β-葡萄糖苷酶
CN105934515A (zh) * 2013-11-26 2016-09-07 美国政府(由卫生和人类服务部的部长所代表) 用于治疗糖原贮积病的腺相关病毒载体
EP3293203A1 (en) * 2016-09-12 2018-03-14 Genethon Acid-alpha glucosidase variants and uses thereof
AU2017322376A1 (en) * 2016-09-12 2019-03-28 Association Institut De Myologie Acid-alpha glucosidase variants and uses thereof
CN113316639A (zh) * 2018-11-16 2021-08-27 阿斯克肋匹奥生物制药公司 用于治疗庞贝氏病的治疗性腺相关病毒

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2687597B1 (en) 2011-03-16 2018-12-26 Amano Enzyme Inc. Modified alpha-glucosidase and applications of same
WO2013151664A1 (en) 2012-04-02 2013-10-10 modeRNA Therapeutics Modified polynucleotides for the production of proteins
JP6342886B2 (ja) * 2012-04-18 2018-06-13 ザ・チルドレンズ・ホスピタル・オブ・フィラデルフィアＴｈｅ Ｃｈｉｌｄｒｅｎ’Ｓ Ｈｏｓｐｉｔａｌ Ｏｆ Ｐｈｉｌａｄｅｌｐｈｉａ Ａａｖカプシドバリアントを使用した高効率な遺伝子導入のための組成物及び方法
WO2016063331A1 (ja) 2014-10-20 2016-04-28 昭和産業株式会社 新規α－グルコシダーゼ
EP3293259A1 (en) * 2016-09-12 2018-03-14 Genethon Acid-alpha glucosidase variants and uses thereof

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
CN105745322A (zh) * 2013-09-17 2016-07-06 易登尼有限公司 用于增加生物质糖化的改良的β-葡萄糖苷酶
CN105934515A (zh) * 2013-11-26 2016-09-07 美国政府(由卫生和人类服务部的部长所代表) 用于治疗糖原贮积病的腺相关病毒载体
WO2015196179A1 (en) * 2014-06-20 2015-12-23 University Of Florida Research Foundation, Inc. Methods of packaging multiple adeno-associated virus vectors
EP3293203A1 (en) * 2016-09-12 2018-03-14 Genethon Acid-alpha glucosidase variants and uses thereof
WO2018046775A1 (en) * 2016-09-12 2018-03-15 Genethon Acid-alpha glucosidase variants and uses thereof
AU2017322376A1 (en) * 2016-09-12 2019-03-28 Association Institut De Myologie Acid-alpha glucosidase variants and uses thereof
CN113316639A (zh) * 2018-11-16 2021-08-27 阿斯克肋匹奥生物制药公司 用于治疗庞贝氏病的治疗性腺相关病毒

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024188025A1 (zh) * 2023-03-14 2024-09-19 北京据德医药科技有限公司 一种重组酸性α-葡萄糖苷酶及其用途

Also Published As

Publication number Publication date
CO2020015707A2 (es) 2021-03-19
JP2021523718A (ja) 2021-09-09
KR20210021310A (ko) 2021-02-25
EP3794043A4 (en) 2022-02-23
MY207355A (en) 2025-02-21
PE20210337A1 (es) 2021-02-19
BR112020023393A2 (pt) 2021-02-09
MX2020012332A (es) 2021-02-26
CL2020002973A1 (es) 2021-07-19
EP3794043A1 (en) 2021-03-24
TW202016310A (zh) 2020-05-01
SG11202011191WA (en) 2020-12-30
WO2019222411A1 (en) 2019-11-21
US20210222141A1 (en) 2021-07-22
PH12020551957A1 (en) 2021-09-20
AU2019268363A1 (en) 2021-01-07
CA3100213A1 (en) 2019-11-21
US20250101396A1 (en) 2025-03-27
JP2025066765A (ja) 2025-04-23
US12084693B2 (en) 2024-09-10

Similar Documents

Publication Publication Date Title
US20250101396A1 (en) Codon-optimized acid alpha-glucosidase expression cassettes and methods of using same
JP6373763B2 (ja) Ａａｖベクター成分、及び、細胞、臓器並びに組織への遺伝子導入のための方法
US12290574B2 (en) Optimized promoter sequences, intron-free expression constructs and methods of use
AU2018304194B2 (en) Apheresis methods and uses
JP2022180543A (ja) 酸性αグルコシダーゼ変異体及びその使用
US20240110201A1 (en) Compositions and Methods for Treating Hereditary Angioedema
JP2024504611A (ja) ファブリー病を治療するための組成物および方法
JP2022512589A (ja) Ｇｍ１ガングリオシドーシスの治療に有用な組成物
US20260131031A1 (en) Aav particles comprising liver-tropic capsid protein and acid alpha-glucosidase and use to treat pompe disease
CN113891712A (zh) 用于晚期婴儿神经元蜡样脂褐质沉积症2型的aav载体治疗方法
KR20240134878A (ko) 오르니틴 트랜스카르바밀라제(otc) 결핍증을 치료하는 방법
RU2823353C2 (ru) КОДОН-ОПТИМИЗИРОВАННЫЕ ЭКСПРЕССИРУЮЩИЕ КАССЕТЫ КИСЛОЙ α-ГЛЮКОЗИДАЗЫ И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
JP2023512043A (ja) ムコ多糖症ｉｖａの治療
TWI813851B (zh) 具有工程化之啟動子之共濟蛋白（ｆｒａｔａｘｉｎ）表現構築體及其使用方法
CN116981770A (zh) 治疗法布里病的组合物和方法
TW202208622A (zh) 用於治療克拉培氏病之組成物
CN117120076A (zh) 用于治疗遗传性血管性水肿的组合物和方法

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication

Application publication date: 20210205

RJ01 Rejection of invention patent application after publication