CN113166759B - 经化学修饰的RNAi构建体及其用途 - Google Patents

经化学修饰的RNAi构建体及其用途 Download PDF

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CN113166759B
CN113166759B CN201980081382.6A CN201980081382A CN113166759B CN 113166759 B CN113166759 B CN 113166759B CN 201980081382 A CN201980081382 A CN 201980081382A CN 113166759 B CN113166759 B CN 113166759B
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nucleotides
rnai construct
nucleotide
positions
antisense strand
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CN113166759A (zh
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J·K·默里
B·吴
Y·程
B·J·赫伯瑞奇
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Amgen Inc
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CN201980081382.6A 2018-12-10 2019-12-09 经化学修饰的RNAi构建体及其用途 Active CN113166759B (zh)

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US201862777677P 2018-12-10 2018-12-10
US62/777677 2018-12-10
PCT/US2019/065294 WO2020123410A1 (en) 2018-12-10 2019-12-09 CHEMICALLY-MODIFIED RNAi CONSTRUCTS AND USES THEREOF

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US (1) US20220049252A1 (https=)
EP (1) EP3894554A1 (https=)
JP (1) JP7814932B2 (https=)
KR (1) KR20210102313A (https=)
CN (2) CN113166759B (https=)
AU (1) AU2019395341B2 (https=)
BR (1) BR112021011043A2 (https=)
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Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT3894549T (pt) 2018-12-10 2024-10-16 Amgen Inc Transposase piggybac mutada
US20230078200A1 (en) * 2019-12-09 2023-03-16 Amgen Inc. RNAi CONSTRUCTS AND METHODS FOR INHIBITING LPA EXPRESSION
MX2022015169A (es) * 2020-06-01 2023-07-03 Amgen Inc Constructos de arni para inhibir la expresion de hsd17b13 y metodos de uso de los mismos.
PE20230993A1 (es) 2020-08-13 2023-06-23 Amgen Inc Construcciones de iarn y metodos para inhibir la expresion de marc1
WO2022098841A1 (en) * 2020-11-05 2022-05-12 Amgen Inc. METHODS FOR TREATING ATHEROSCLEROTIC CARDIOVASCULAR DISEASE WITH LPA-TARGETED RNAi CONSTRUCTS
AU2022212580A1 (en) * 2021-01-30 2023-07-27 E-Therapeutics Plc Nucleic acids containing abasic nucleotides
EP4294449A1 (en) * 2021-02-18 2023-12-27 Oneglobe Holdings Limited Compositions for conjugating oligonucleotides and carbohydrates
AU2022308807B2 (en) * 2021-07-08 2026-02-12 Olix Pharmaceuticals, Inc. Rnai agent targeting marc1 gene, and use thereof
IL312811A (en) 2021-11-16 2024-07-01 Shanghai Argo Biopharmaceutical Co Ltd Composition and method for inhibiting angiotensinogen (agt) protein expression
CN114703184B (zh) * 2022-03-11 2024-06-18 厦门甘宝利生物医药有限公司 Lpa抑制剂及其用途
WO2023207615A1 (zh) * 2022-04-26 2023-11-02 南京明德新药研发有限公司 一类含由天然核苷酸组成突出端的双链RNAi化合物
IL317825A (en) 2022-07-25 2025-02-01 Amgen Inc RNA interference constructs and methods for inhibiting fam13a expression
JP2025524135A (ja) * 2022-07-27 2025-07-25 イー－セラピューティクス・ピーエルシー 核酸化合物
IL318229A (en) * 2022-07-27 2025-03-01 E Therapeutics Plc Nucleic acid compounds
AU2023343825A1 (en) * 2022-09-20 2025-03-13 Shanghai Argo Biopharmaceutical Co., Ltd. Specifically modified rnai reagent and composition
CN120265773A (zh) * 2022-10-14 2025-07-04 美国圣因生物股份有限公司 靶向c3的小干扰rna及其用途
WO2024140101A1 (zh) * 2022-12-28 2024-07-04 北京炫景瑞医药科技有限公司 修饰的双链寡核苷酸分子、修饰的双链寡核苷酸缀合物及其用途
WO2024240056A1 (zh) 2023-05-19 2024-11-28 深圳信立泰药业股份有限公司 一种磺酰胺类化合物及其制备方法和医药用途
WO2024240212A1 (zh) * 2023-05-24 2024-11-28 云合智药（苏州）生物科技有限公司 用于抑制angptl3表达的rnai剂及其应用
WO2025113470A1 (en) * 2023-11-27 2025-06-05 Shanghai Argo Biopharmaceutical Co., Ltd. Compositions and methods for inhibiting expression of transthyretin (ttr)
WO2025232837A1 (zh) * 2024-05-08 2025-11-13 深圳信立泰药业股份有限公司 经修饰的siRNA及其制备方法和用途
WO2025260042A1 (en) 2024-06-14 2025-12-18 Amgen Inc. Rnai constructs and methods for inhibiting cnr1 expression
WO2026002138A1 (zh) * 2024-06-27 2026-01-02 成都新泽利医药科技有限公司 特定修饰的双链寡核苷酸及其组合物

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013074974A2 (en) * 2011-11-18 2013-05-23 Alnylam Pharmaceuticals, Inc. Modified rnai agents
WO2016028649A1 (en) * 2014-08-20 2016-02-25 Alnylam Pharmaceuticals, Inc. Modified double-stranded rna agents

Family Cites Families (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5719262A (en) 1993-11-22 1998-02-17 Buchardt, Deceased; Ole Peptide nucleic acids having amino acid side chains
US5714331A (en) 1991-05-24 1998-02-03 Buchardt, Deceased; Ole Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5981505A (en) 1993-01-26 1999-11-09 The Trustees Of The University Of Pennsylvania Compositions and methods for delivery of genetic material
US5837533A (en) 1994-09-28 1998-11-17 American Home Products Corporation Complexes comprising a nucleic acid bound to a cationic polyamine having an endosome disruption agent
US5840710A (en) 1994-12-09 1998-11-24 Genzyme Corporation Cationic amphiphiles containing ester or ether-linked lipophilic groups for intracellular delivery of therapeutic molecules
US7422902B1 (en) 1995-06-07 2008-09-09 The University Of British Columbia Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer
ATE285477T1 (de) 1995-06-07 2005-01-15 Inex Pharmaceutical Corp Herstellung von lipid-nukleinsäure partikeln duch ein hydrophobische lipid-nukleinsäuree komplexe zwischenprodukt und zur verwendung in der gentransfer
US5981501A (en) 1995-06-07 1999-11-09 Inex Pharmaceuticals Corp. Methods for encapsulating plasmids in lipid bilayers
US6217900B1 (en) 1997-04-30 2001-04-17 American Home Products Corporation Vesicular complexes and methods of making and using the same
DE69834038D1 (de) 1997-07-01 2006-05-18 Isis Pharmaceutical Inc Zusammensetzungen und verfahren zur verabreichung von oligonukleotiden über die speiseröhre
US7491805B2 (en) 2001-05-18 2009-02-17 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US7833992B2 (en) 2001-05-18 2010-11-16 Merck Sharpe & Dohme Conjugates and compositions for cellular delivery
US6693187B1 (en) 2000-10-17 2004-02-17 Lievre Cornu Llc Phosphinoamidite carboxlates and analogs thereof in the synthesis of oligonucleotides having reduced internucleotide charge
US20030130186A1 (en) 2001-07-20 2003-07-10 Chandra Vargeese Conjugates and compositions for cellular delivery
US7109165B2 (en) 2001-05-18 2006-09-19 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US9181551B2 (en) 2002-02-20 2015-11-10 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
WO2003093449A2 (en) 2002-05-06 2003-11-13 Nucleonics, Inc. Methods for delivery of nucleic acids
US8017762B2 (en) 2003-04-17 2011-09-13 Alnylam Pharmaceuticals, Inc. Modified iRNA agents
US7723509B2 (en) 2003-04-17 2010-05-25 Alnylam Pharmaceuticals IRNA agents with biocleavable tethers
DK1620544T3 (en) 2003-04-17 2019-01-14 Alnylam Pharmaceuticals Inc MODIFIED iRNA AGENTS
US7851615B2 (en) 2003-04-17 2010-12-14 Alnylam Pharmaceuticals, Inc. Lipophilic conjugated iRNA agents
CA2685127C (en) 2007-04-23 2019-01-08 Alnylam Pharmaceuticals, Inc. Glycoconjugates of rna interference agents
WO2009082607A2 (en) 2007-12-04 2009-07-02 Alnylam Pharmaceuticals, Inc. Targeting lipids
JP2012517822A (ja) * 2009-02-19 2012-08-09 ガラパゴス・ナムローゼ・フェンノートシャップ 炎症を包含する疾患の診断及び治療に有用な同定方法及び化合物
AR090905A1 (es) 2012-05-02 2014-12-17 Merck Sharp & Dohme Conjugados que contienen tetragalnac y peptidos y procedimientos para la administracion de oligonucleotidos, composicion farmaceutica
EP3564374A1 (en) 2013-06-21 2019-11-06 Ionis Pharmaceuticals, Inc. Compositions and methods for modulation of target nucleic acids
CA2997444A1 (en) 2015-09-29 2017-04-06 Amgen Inc. Asgr inhibitors for reducing cholesterol levels
UY37376A (es) 2016-08-26 2018-03-23 Amgen Inc Construcciones de arni para inhibir expresión de asgr1 y métodos para su uso

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013074974A2 (en) * 2011-11-18 2013-05-23 Alnylam Pharmaceuticals, Inc. Modified rnai agents
WO2016028649A1 (en) * 2014-08-20 2016-02-25 Alnylam Pharmaceuticals, Inc. Modified double-stranded rna agents

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