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

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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
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nucleic acid
gaa
aav
sequence
cpg dinucleotides
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Chinese (zh)
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泽维尔·安谷拉
肖恩·阿穆尔
杰梅·诺丁
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Spark Therapeutics Inc
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Spark Therapeutics Inc
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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

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CN112334489A true CN112334489A (zh) 2021-02-05

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

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
DK3635009T3 (da) 2017-06-07 2026-03-30 Regeneron Pharma Sammensætninger og fremgangsmåder til internalisering af enzymer
US12258597B2 (en) 2018-02-07 2025-03-25 Regeneron Pharmaceuticals, Inc. Methods and compositions for therapeutic protein delivery
BR112020023145A2 (pt) 2018-05-17 2021-02-02 Regeneron Pharmaceuticals, Inc. anticorpo anti-cd63 ou fragmento de ligação ao antígeno do mesmo, molécula de ligação ao antígeno biespecífica, proteína terapêutica de múltiplos domínios, polinucleotídeo composição farmacêutica, e, composto
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
BR112021003399A2 (pt) 2018-08-24 2021-05-18 Spark Therapeutics, Inc. sequências de promotores otimizadas, construtos de expressão livres de íntron e métodos de uso
EP3996696A1 (en) * 2019-07-09 2022-05-18 Genethon Treatment of glycogen storage disease (gsd)
JP2023507575A (ja) 2019-12-20 2023-02-24 コデクシス， インコーポレイテッド 操作された酸性アルファ－グルコシダーゼバリアント
MX2023008362A (es) * 2021-01-14 2023-10-04 Spark Therapeutics Inc Composiciones y metodos para el tratamiento de la enfermedad de fabry.
CR20240137A (es) * 2021-08-20 2024-07-29 Biocad Joint Stock Co Método para obtener una cápside de virus adenoasociado modificada
CA3229998A1 (en) * 2021-08-25 2023-03-02 Canbridge Pharmaceuticals, Inc. Aav particles comprising a liver-tropic capsid protein and alpha-galactosidase and their use to treat fabry disease
AR126877A1 (es) * 2021-08-25 2023-11-22 Canbridge Pharmaceuticals Inc PARTÍCULAS DE AAV QUE COMPRENDEN UNA PROTEÍNA DE LA CÁPSIDE HEPATOTRÓPICA Y a-GLUCOSIDASA ÁCIDA (GAA) Y SU USO PARA TRATAR LA ENFERMEDAD DE POMPE
CA3242731A1 (en) * 2022-02-02 2023-08-10 Regeneron Pharmaceuticals, Inc. 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
CN103443273B (zh) 2011-03-16 2016-10-26 天野酶制品株式会社 修饰型α-葡萄糖苷酶及其用途
WO2013151665A2 (en) * 2012-04-02 2013-10-10 modeRNA Therapeutics Modified polynucleotides for the production of proteins associated with human disease
NZ701693A (en) * 2012-04-18 2017-02-24 The Children’S Hospital Of Philadelphia Composition and methods for highly efficient gene transfer using aav capsid variants
EP3211076A4 (en) 2014-10-20 2018-03-21 Showa Sangyo Co., Ltd. Novel alpha-glucosidase
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

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

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