TW202132567A - 亨汀頓蛋白(HTT)iRNA劑組成物及其使用方法 - Google Patents

亨汀頓蛋白(HTT)iRNA劑組成物及其使用方法 Download PDF

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TW202132567A
TW202132567A TW109137670A TW109137670A TW202132567A TW 202132567 A TW202132567 A TW 202132567A TW 109137670 A TW109137670 A TW 109137670A TW 109137670 A TW109137670 A TW 109137670A TW 202132567 A TW202132567 A TW 202132567A
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nucleotides
dsrna agent
strand
antisense strand
agent according
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曼葛拉 蜜納柯斯西 索拉帕迪恩
詹姆斯 D 麥克尼奇
布萊特 李 博斯特威克
馬克K 史奇蓋爾
艾登 卡斯特瑞諾
杰弗里 祖柏
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美商阿尼拉製藥公司
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TW109137670A 2019-11-01 2020-10-29 亨汀頓蛋白(HTT)iRNA劑組成物及其使用方法 TW202132567A (zh)

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US201962929174P 2019-11-01 2019-11-01
US62/929,174 2019-11-01

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US (1) US20220380762A1 (enExample)
EP (1) EP4051795A1 (enExample)
JP (2) JP7830319B2 (enExample)
KR (1) KR20220094213A (enExample)
CN (2) CN114728018B (enExample)
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AU (1) AU2020376840A1 (enExample)
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IL307239A (en) 2021-03-29 2023-11-01 Alnylam Pharmaceuticals Inc Preparations containing Huntingtin IRNA factor (HTT) and methods of using them
EP4341401A1 (en) * 2021-05-18 2024-03-27 Alnylam Pharmaceuticals, Inc. Sodium-glucose cotransporter-2 (sglt2) irna compositions and methods of use thereof
MX2024003519A (es) 2021-09-24 2024-04-01 Alnylam Pharmaceuticals Inc Composiciones de agentes de acido ribonucleico de interferencia (arni) de proteina tau asociada a microtubulos (mapt) y sus metodos de uso.
WO2024156083A1 (en) * 2023-01-27 2024-08-02 Beijing Jitai Pharmaceutical Technology Co., Ltd. Ai-assisted design of lnps for effective cns delivery of rna
CN118853663A (zh) * 2023-04-28 2024-10-29 北京福元医药股份有限公司 用于抑制marc1基因表达的双链核糖核酸及其修饰物、缀合物和用途
WO2025090567A1 (en) * 2023-10-23 2025-05-01 Ophidion Inc. LOW DOSE siRNA TREATMENTS OF HUNTINGTON'S DISEASE
TW202532088A (zh) * 2024-02-07 2025-08-16 大陸商上海舶望製藥有限公司 抑制亨廷頓蛋白(htt)表達的組合物和方法
WO2025170027A1 (ja) * 2024-02-08 2025-08-14 テルモ株式会社 オリゴヌクレオチド
WO2025265013A2 (en) * 2024-06-20 2025-12-26 Arrowhead Pharmaceuticals, Inc. Rnai agents for inhibiting expression of huntingtin (htt), compositions thereof, and methods of use

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