TW202143984A - 微管相關蛋白TAU (MAPT) iRNA劑組合物及其使用方法 - Google Patents

微管相關蛋白TAU (MAPT) iRNA劑組合物及其使用方法 Download PDF

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TW202143984A
TW202143984A TW110111671A TW110111671A TW202143984A TW 202143984 A TW202143984 A TW 202143984A TW 110111671 A TW110111671 A TW 110111671A TW 110111671 A TW110111671 A TW 110111671A TW 202143984 A TW202143984 A TW 202143984A
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nucleotides
dsrna agent
strand
antisense strand
mapt
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TW110111671A
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曼歌拉 米納科希 桑德拉潘迪恩
詹母士 Ｄ 馬克辛尼克
伊蓮 費雪維克
亞當 克斯拓雷諾
察拉藍伯斯 凱特妮思
馬克 Ｋ 史齊歌
強納森 愛德華 斐爾禮
傑佛瑞 祖伯
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美商艾爾妮蘭製藥公司
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TW110111671A 2020-03-30 2021-03-30 微管相關蛋白TAU (MAPT) iRNA劑組合物及其使用方法 TW202143984A (zh)

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US202063002030P 2020-03-30 2020-03-30
US63/002,030 2020-03-30
US202163164467P 2021-03-22 2021-03-22
US63/164,467 2021-03-22

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US (1) US20230203486A1 (https=)
EP (1) EP4126230A4 (https=)
JP (1) JP2023521604A (https=)
KR (1) KR20230005194A (https=)
CN (1) CN116234585A (https=)
AU (1) AU2021246024A1 (https=)
BR (1) BR112022019606A2 (https=)
CA (1) CA3178304A1 (https=)
IL (1) IL296851A (https=)
MX (1) MX2022012293A (https=)
TW (1) TW202143984A (https=)
WO (1) WO2021202511A2 (https=)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW202328449A (zh) * 2021-09-24 2023-07-16 美商艾拉倫製藥公司 微管相關蛋白ＴＡＵ（ＭＡＰＴ）ｉＲＮＡ試劑組合物及其使用方法
WO2023064707A1 (en) * 2021-10-07 2023-04-20 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing tau expression
US20230212576A1 (en) 2021-12-13 2023-07-06 Eli Lilly And Company Mapt rna interference agents
JP2025507372A (ja) 2022-02-11 2025-03-18 アルナイラム ファーマシューティカルズ， インコーポレイテッド 微小管関連タンパク質タウ（ＭＡＰＴ）ｉＲＮＡ剤組成物およびその使用方法
KR20240154674A (ko) * 2022-03-16 2024-10-25 얀센 파마슈티카 엔브이 MAPT siRNA 및 이의 용도
KR20250129743A (ko) * 2022-12-29 2025-08-29 보이저 테라퓨틱스, 인크. Mapt를 조절하기 위한 조성물 및 방법
WO2024201423A2 (en) * 2023-03-30 2024-10-03 Biorchestra Co., Ltd. Microtubule-associated protein tau targeting sirnas and uses thereof
TW202448484A (zh) * 2023-04-20 2024-12-16 美商雅迪克斯製藥公司 Ｍａｐｔ調節組合物及其使用方法
AU2024315297A1 (en) * 2023-08-01 2026-02-12 Tuojie Biotech (Shanghai) Co., Ltd. Dsrna targeting mapt and pharmaceutical use thereof
WO2025027577A1 (en) * 2023-08-02 2025-02-06 Consejo Nacional De Investigaciones Científicas Y Técnicas (Conicet) Micrornas designed against the microtubule-associated protein tau for the treatment of tauopathies
WO2025077806A1 (en) * 2023-10-11 2025-04-17 Shanghai Argo Biopharmaceutical Co., Ltd. Compositions and methods for inhibiting expression of microtubule associated protein tau (mapt)
US12551569B2 (en) * 2024-03-31 2026-02-17 Arrowhead Pharmaceuticals, Inc. RNAi agents for inhibiting expression of microtubule associated protein tau (MAPT), compositions thereof, and methods of use
WO2025233849A2 (en) * 2024-05-07 2025-11-13 Janssen Pharmaceutica Nv MAPT siRNA AND USES THEREOF
WO2026010722A1 (en) * 2024-07-03 2026-01-08 Voyager Therapeutics, Inc. Compositions and methods for regulating mapt
WO2026017176A1 (zh) * 2024-07-19 2026-01-22 北京安龙生物医药有限公司 靶向微管相关蛋白Tau基因的寡核苷酸及其用途
CN121780524A (zh) * 2024-08-02 2026-04-03 北京尧景基因技术有限公司 抑制MAPT基因表达的siRNA及其缀合物和应用
WO2026067655A1 (zh) * 2024-09-26 2026-04-02 大睿生物医药科技(上海)有限公司 调控TAU表达的dsRNA分子

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101346393B (zh) * 2005-11-02 2015-07-22 普洛体维生物治疗公司 修饰的siRNA分子及其应用
GB0605337D0 (en) * 2006-03-17 2006-04-26 Genomica Sau Treatment of CNS conditions
EP2831232A4 (en) * 2012-03-30 2015-11-04 Univ Washington METHOD FOR MODULATING TAU EXPRESSION TO REDUCE PROBLEMS AND MODIFY A NEURODEGENERATIVE SYNDROME
US9133461B2 (en) * 2012-04-10 2015-09-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the ALAS1 gene
CN105264091B (zh) * 2013-03-14 2020-02-28 Ionis制药公司 用于调节tau表达的组合物和方法
US9951330B2 (en) * 2013-07-11 2018-04-24 The Trustees Of Columbia University In The City Of New York Micrornas that silence tau expression
TW202246503A (zh) * 2013-07-19 2022-12-01 美商百健Ｍａ公司 用於調節τ蛋白表現之組合物
WO2015038892A1 (en) * 2013-09-13 2015-03-19 Moderna Therapeutics, Inc. Polynucleotide compositions containing amino acids
IL316808A (en) * 2014-08-20 2025-01-01 Alnylam Pharmaceuticals Inc Modified double-stranded RNA materials and their uses
US11077132B2 (en) * 2015-02-04 2021-08-03 F. Hoffmann-La Roche Ag Tau antisense oligomers and uses thereof
US10513701B2 (en) * 2015-03-25 2019-12-24 Università Degli Studi Di Trento RNA interference mediated therapy for neurodegenerative diseases
IL320434A (en) * 2015-07-22 2025-06-01 Wave Life Sciences Ltd Oligonucleotide preparations and methods
PH12018501207B1 (en) * 2015-12-21 2024-02-23 Novartis Ag Compositions and methods for decreasing tau expression
EP3728281A1 (en) * 2017-12-21 2020-10-28 Alnylam Pharmaceuticals Inc. Chirally-enriched double-stranded rna agents
PE20210346A1 (es) * 2018-07-03 2021-02-25 Hoffmann La Roche Oligonucleotidos para modular la expresion de tau
US20230099372A1 (en) * 2020-02-07 2023-03-30 Biorchestra Co., Ltd. Use of mirna-485 inhibitors for treating tauopathy
US20210363523A1 (en) * 2020-03-18 2021-11-25 University Of Massachusetts Oligonucleotides for mapt modulation

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US20230203486A1 (en) 2023-06-29
CA3178304A1 (en) 2021-10-07
MX2022012293A (es) 2022-10-27
WO2021202511A3 (en) 2021-11-25
AU2021246024A1 (en) 2022-10-27
IL296851A (en) 2022-11-01
KR20230005194A (ko) 2023-01-09
CN116234585A (zh) 2023-06-06
EP4126230A4 (en) 2025-07-30
JP2023521604A (ja) 2023-05-25
WO2021202511A2 (en) 2021-10-07
BR112022019606A2 (pt) 2022-11-16
EP4126230A2 (en) 2023-02-08

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