JP7289610B2 - 修飾二本鎖rna剤 - Google Patents

修飾二本鎖rna剤 Download PDF

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JP7289610B2
JP7289610B2 JP2017509743A JP2017509743A JP7289610B2 JP 7289610 B2 JP7289610 B2 JP 7289610B2 JP 2017509743 A JP2017509743 A JP 2017509743A JP 2017509743 A JP2017509743 A JP 2017509743A JP 7289610 B2 JP7289610 B2 JP 7289610B2
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ome
antisense strand
positions
dsrna agent
dsrna
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JP2017525705A5 (enExample
JP2017525705A (ja
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マルティン・マイアー
ドン・フォスター
スチュアート・ミルスタイン
サティア・クチマンチ
バサント・ジャダブ
カラントッタティル・ラジーブ
ムティア・マノハラン
ルビーナ・パルマル
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Alnylam Pharmaceuticals Inc
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Alnylam Pharmaceuticals Inc
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Publication of JP2017525705A publication Critical patent/JP2017525705A/ja
Publication of JP2017525705A5 publication Critical patent/JP2017525705A5/ja
Priority to JP2020212528A priority Critical patent/JP7672220B2/ja
Priority to JP2020212527A priority patent/JP7370311B2/ja
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Publication of JP7289610B2 publication Critical patent/JP7289610B2/ja
Priority to JP2023178574A priority patent/JP7654744B2/ja
Priority to JP2025044214A priority patent/JP2025111426A/ja
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JP2017509743A 2014-08-20 2015-08-14 修飾二本鎖rna剤 Active JP7289610B2 (ja)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP2020212528A JP7672220B2 (ja) 2014-08-20 2020-12-22 修飾二本鎖rna剤
JP2020212527A JP7370311B2 (ja) 2014-08-20 2020-12-22 修飾二本鎖rna剤
JP2023178574A JP7654744B2 (ja) 2014-08-20 2023-10-17 修飾二本鎖rna剤
JP2025044214A JP2025111426A (ja) 2014-08-20 2025-03-19 修飾二本鎖rna剤

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201462039507P 2014-08-20 2014-08-20
US62/039,507 2014-08-20
US201462083744P 2014-11-24 2014-11-24
US62/083,744 2014-11-24
US201462093919P 2014-12-18 2014-12-18
US62/093,919 2014-12-18
PCT/US2015/045407 WO2016028649A1 (en) 2014-08-20 2015-08-14 Modified double-stranded rna agents

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JP2020212527A Division JP7370311B2 (ja) 2014-08-20 2020-12-22 修飾二本鎖rna剤
JP2020212528A Division JP7672220B2 (ja) 2014-08-20 2020-12-22 修飾二本鎖rna剤

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JP2017525705A JP2017525705A (ja) 2017-09-07
JP2017525705A5 JP2017525705A5 (enExample) 2018-09-20
JP7289610B2 true JP7289610B2 (ja) 2023-06-12

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JP2017509743A Active JP7289610B2 (ja) 2014-08-20 2015-08-14 修飾二本鎖rna剤
JP2020212528A Active JP7672220B2 (ja) 2014-08-20 2020-12-22 修飾二本鎖rna剤
JP2020212527A Active JP7370311B2 (ja) 2014-08-20 2020-12-22 修飾二本鎖rna剤
JP2023178574A Active JP7654744B2 (ja) 2014-08-20 2023-10-17 修飾二本鎖rna剤
JP2025044214A Pending JP2025111426A (ja) 2014-08-20 2025-03-19 修飾二本鎖rna剤

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JP2020212528A Active JP7672220B2 (ja) 2014-08-20 2020-12-22 修飾二本鎖rna剤
JP2020212527A Active JP7370311B2 (ja) 2014-08-20 2020-12-22 修飾二本鎖rna剤
JP2023178574A Active JP7654744B2 (ja) 2014-08-20 2023-10-17 修飾二本鎖rna剤
JP2025044214A Pending JP2025111426A (ja) 2014-08-20 2025-03-19 修飾二本鎖rna剤

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US (11) US10233448B2 (enExample)
EP (4) EP3186377A1 (enExample)
JP (5) JP7289610B2 (enExample)
KR (3) KR102494171B1 (enExample)
CN (3) CN114181942B (enExample)
CA (1) CA2958758A1 (enExample)
EA (1) EA201790420A1 (enExample)
IL (3) IL316808A (enExample)
MX (3) MX2017002144A (enExample)
NZ (1) NZ730296A (enExample)
SG (3) SG11201701166UA (enExample)
WO (1) WO2016028649A1 (enExample)

Families Citing this family (140)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2739895C (en) 2008-10-20 2018-09-25 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of transthyretin
MX345095B (es) 2011-06-21 2017-01-17 Alnylam Pharmaceuticals Inc Composiciones de arni similares a angiopoyetina 3 (angptl3) y metodos para su uso.
SI3366775T2 (sl) 2011-11-18 2025-12-31 Alnylam Pharmaceuticals, Inc. Modificirana sredstva RNAI
CN104661664B (zh) 2012-07-13 2020-07-03 波涛生命科学有限公司 手性控制
KR102295648B1 (ko) 2013-05-22 2021-08-31 알닐람 파마슈티칼스 인코포레이티드 SERPINA1 iRNA 조성물 및 이의 사용 방법
IL316808A (en) * 2014-08-20 2025-01-01 Alnylam Pharmaceuticals Inc Modified double-stranded RNA materials and their uses
EP3929293A3 (en) 2015-04-03 2022-03-16 University Of Massachusetts Fully stabilized asymmetric sirna
JP6975641B2 (ja) 2015-04-13 2021-12-01 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Alnylam Pharmaceuticals, Inc. アンギオポエチン様3(ANGPTL3)iRNA組成物およびそれらの使用方法
HUE051998T2 (hu) 2015-07-31 2021-04-28 Alnylam Pharmaceuticals Inc Transztiretin (TTR) iRNS készítmények és eljárások azok alkalmazása TTR-asszociált betegségek kezelésére vagy megelõzésére
EP3334499A4 (en) 2015-08-14 2019-04-17 University of Massachusetts BIOACTIVE CONJUGATES FOR THE RELEASE OF OLIGONUCLEOTIDES
HK1258758A1 (zh) 2016-01-31 2019-11-22 University Of Massachusetts 分支的寡核苷酸
MX2018009325A (es) * 2016-02-01 2019-05-15 Arrakis Therapeutics Inc Compuestos y metodos para tratar enfermedades mediadas por el acido ribonucleico (arn).
MA45470A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Acides nucléiques kras et leurs utilisations
MA45328A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Compositions acide nucléique-polypeptide et utilisations de celles-ci
MA45469A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Acides nucléiques de bêta-caténine et leurs utilisations
MA45349A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Acides nucléiques egfr et leurs utilisations
CA3023764A1 (en) 2016-06-06 2017-12-14 Arrowhead Pharmaceuticals, Inc. 5'-cyclo-phosphonate modified nucleotides
WO2018031933A2 (en) 2016-08-12 2018-02-15 University Of Massachusetts Conjugated oligonucleotides
WO2018035380A1 (en) * 2016-08-17 2018-02-22 Solstice Biologics, Ltd. Polynucleotide constructs
US10131911B2 (en) * 2016-11-07 2018-11-20 nanoSUR LLC Post-transcriptionally chemically modified double strand RNAs
WO2018089582A1 (en) 2016-11-10 2018-05-17 San Diego State University Research Foundation Compounds for fluorescence sensing of duplex formation
TWI788312B (zh) * 2016-11-23 2023-01-01 美商阿尼拉製藥公司 絲胺酸蛋白酶抑制因子A1 iRNA組成物及其使用方法
KR102645243B1 (ko) * 2016-11-23 2024-03-11 알닐람 파마슈티칼스 인코포레이티드 표적외 효과가 감소된 변형 rna 작용제
EP3554561B1 (en) 2016-12-14 2023-06-28 Janssen Biotech, Inc. Cd137 binding fibronectin type iii domains
JP7104703B2 (ja) 2016-12-14 2022-07-21 ヤンセン バイオテツク,インコーポレーテツド Cd8a結合フィブロネクチンiii型ドメイン
EP3555292A1 (en) * 2016-12-16 2019-10-23 Alnylam Pharmaceuticals, Inc. Methods for treating or preventing ttr-associated diseases using transthyretin (ttr) irna compositions
CN110520531A (zh) * 2017-04-05 2019-11-29 赛伦斯治疗有限责任公司 产品和组合物
PL3607068T3 (pl) * 2017-04-05 2023-03-20 Silence Therapeutics Gmbh Hamowanie TMPRSS6 mediowane interferencją RNA
EP3550022A1 (en) * 2018-04-05 2019-10-09 Silence Therapeutics GmbH Products and compositions
CN110799647A (zh) 2017-06-23 2020-02-14 马萨诸塞大学 双尾自递送sirna及相关的方法
US11597744B2 (en) 2017-06-30 2023-03-07 Sirius Therapeutics, Inc. Chiral phosphoramidite auxiliaries and methods of their use
KR20250004009A (ko) 2017-09-14 2025-01-07 애로우헤드 파마슈티컬스 인코포레이티드 안지오포이에틴-유사 3 (ANGPTL3)의 발현을 억제하기 위한 RNAi 작용제 및 조성물, 및 사용 방법
WO2019060442A1 (en) 2017-09-19 2019-03-28 Alnylam Pharmaceuticals, Inc. COMPOSITIONS AND METHODS FOR TREATMENT OF TRANSTHYRETIN MEDIATED AMYLOSIS (TTR)
US11110180B2 (en) * 2017-10-04 2021-09-07 Avidity Biosciences Inc. Nucleic acid-polypeptide compositions and uses thereof
US11873489B2 (en) * 2017-11-13 2024-01-16 Silence Therapeutics Gmbh Nucleic acids for inhibiting expression of a target gene comprising phosphorodithioate linkages
SG11202003664TA (en) 2017-11-30 2020-05-28 Arrakis Therapeutics Inc Nucleic acid-binding photoprobes and uses thereof
CN110997919B (zh) * 2017-12-01 2024-04-02 苏州瑞博生物技术股份有限公司 双链寡核苷酸、含双链寡核苷酸的组合物与缀合物及制备方法和用途
CN110997917B (zh) * 2017-12-01 2024-04-09 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
CN111050807B (zh) * 2017-12-01 2024-05-28 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
CN110944675B9 (zh) * 2017-12-01 2024-08-09 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
CN110945130B (zh) * 2017-12-01 2024-04-09 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
WO2019105403A1 (zh) * 2017-12-01 2019-06-06 苏州瑞博生物技术有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
HRP20250192T1 (hr) 2017-12-01 2025-04-11 Suzhou Ribo Life Science Co., Ltd. Nukleinska kiselina, sastav i konjugat koji je sadrži, te metoda pripreme i uporaba
MA51103A (fr) 2017-12-06 2020-10-14 Avidity Biosciences Inc Compositions et procédés de traitement de l'atrophie musculaire et de la dystrophie myotonique
CA3086485A1 (en) * 2017-12-21 2019-06-27 Alnylam Pharmaceuticals, Inc. Chirally-enriched double-stranded rna agents
WO2019127004A1 (zh) * 2017-12-26 2019-07-04 广州市锐博生物科技有限公司 修饰的寡核苷酸和可用于合成修饰的寡核苷酸的化合物
CN116375774B (zh) 2017-12-29 2025-09-23 苏州瑞博生物技术股份有限公司 缀合物及其制备方法和用途
CN112055597A (zh) * 2018-03-02 2020-12-08 迪克纳制药公司 用于治疗胆管缺乏相关病况的方法和组合物
EP3775209A1 (en) * 2018-04-05 2021-02-17 Silence Therapeutics GmbH Sirnas with at least two ligands at different ends
EP3775207A1 (en) * 2018-04-05 2021-02-17 Silence Therapeutics GmbH Sirnas with vinylphosphonate at the 5' end of the antisense strand
US12397013B2 (en) 2018-05-07 2025-08-26 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
US12173287B2 (en) 2018-05-07 2024-12-24 Alnylam Pharmaceuticals, Inc. Compositions and methods for improving strand biased
US12247203B2 (en) 2018-05-16 2025-03-11 Alnylam Pharmaceuticals, Inc. Modified RNA agents with reduced off-target effect
WO2020038377A1 (zh) 2018-08-21 2020-02-27 苏州瑞博生物技术有限公司 一种核酸、含有该核酸的药物组合物和缀合物及其用途
US11279930B2 (en) * 2018-08-23 2022-03-22 University Of Massachusetts O-methyl rich fully stabilized oligonucleotides
JP7470107B2 (ja) * 2018-09-28 2024-04-17 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 トランスサイレチン(TTR)iRNA組成物及びTTR関連眼疾患を治療又は予防するためのその使用方法
CN111655297A (zh) * 2018-09-30 2020-09-11 苏州瑞博生物技术有限公司 一种siRNA缀合物及其制备方法和用途
AU2019376628B2 (en) * 2018-11-09 2025-08-07 Alnylam Pharmaceuticals, Inc. Modified double stranded oligonucleotides
CA3122393A1 (en) * 2018-12-10 2020-06-18 Amgen Inc. Chemically-modified rnai constructs and uses thereof
EP3898979A4 (en) * 2018-12-19 2022-10-12 Alnylam Pharmaceuticals, Inc. Amyloid precursor protein (app) rnai agent compositions and methods of use thereof
DK3897672T5 (da) 2018-12-20 2024-08-05 Vir Biotechnology Inc Hbv kombinationsbehandling
WO2020135581A1 (zh) * 2018-12-28 2020-07-02 苏州瑞博生物技术有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
CN111378657B (zh) * 2018-12-28 2024-03-15 苏州瑞博生物技术股份有限公司 抑制COL1A1基因表达的siRNA、含有该siRNA的药物组合物及其用途
US12496347B2 (en) 2018-12-28 2025-12-16 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, composition and conjugate containing nucleic acid, preparation method therefor and use thereof
CN111378658B (zh) * 2018-12-28 2024-03-15 苏州瑞博生物技术股份有限公司 抑制TIMP-1基因表达的siRNA、含有该siRNA的药物组合物及其用途
CN111378655B (zh) * 2018-12-28 2024-03-19 苏州瑞博生物技术股份有限公司 抑制CTGF基因表达的siRNA、含有该siRNA的药物组合物及其用途
CN111378659B (zh) * 2018-12-29 2024-01-30 苏州瑞博生物技术股份有限公司 抑制stat3基因表达的核酸、含有该核酸的药物组合物及其用途
EP3911747A4 (en) 2019-01-18 2023-05-24 University Of Massachusetts DYNAMIC PHARMACOKINETICS-MODIFYING ANCHORS
CN113330117B (zh) * 2019-01-18 2024-05-28 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
JP2022528487A (ja) * 2019-03-29 2022-06-13 ユニバーシティ・オブ・マサチューセッツ C9orf72のオリゴヌクレオチドベースの調節
US11629347B2 (en) 2019-05-06 2023-04-18 University Of Massachusetts Anti-C9ORF72 oligonucleotides and related methods
SG11202112240VA (en) * 2019-05-13 2021-12-30 Vir Biotechnology Inc Compositions and methods for treating hepatitis b virus (hbv) infection
CA3138915A1 (en) * 2019-05-17 2020-11-26 Alnylam Pharmaceuticals, Inc. Oral delivery of oligonucleotides
CN113227376B (zh) * 2019-05-22 2024-04-09 苏州瑞博生物技术股份有限公司 核酸、药物组合物与缀合物及制备方法和用途
EP3974530A4 (en) * 2019-05-22 2023-07-12 Suzhou Ribo Life Science Co., Ltd. NUCLEIC ACID, PHARMACEUTICAL COMPOSITION, CONJUGATE, METHOD FOR PREPARATION AND USE
CN111973619B (zh) * 2019-05-23 2024-01-30 苏州瑞博生物技术股份有限公司 核酸、含有该核酸的药物组合物与siRNA缀合物及制备方法和用途
CN113891939B (zh) * 2019-05-24 2024-04-02 苏州瑞博生物技术股份有限公司 核酸、药物组合物与缀合物及制备方法和用途
WO2020238763A1 (zh) * 2019-05-24 2020-12-03 苏州瑞博生物技术股份有限公司 核酸、药物组合物与缀合物及制备方法和用途
CN112007040B (zh) * 2019-05-31 2024-01-30 苏州瑞博生物技术股份有限公司 用于治疗乙型病毒性肝炎的联合用药物
WO2020247818A1 (en) 2019-06-06 2020-12-10 Avidity Biosciences, Inc. Una amidites and uses thereof
WO2020247782A1 (en) 2019-06-06 2020-12-10 Avidity Biosciences, Inc. Nucleic acid-polypeptide compositions and uses thereof
CA3138627A1 (en) * 2019-06-21 2020-12-24 Alexander V. KEL'IN Structurally defined sirna-dual variable domain immunoglobulin conjugates
KR20220047989A (ko) 2019-08-09 2022-04-19 유니버시티 오브 매사추세츠 Snp를 표적화하는 화학적으로 변형된 올리고뉴클레오타이드
EP4013767A4 (en) 2019-08-15 2023-10-25 Ionis Pharmaceuticals, Inc. Linkage modified oligomeric compounds and uses thereof
US12365894B2 (en) 2019-09-16 2025-07-22 University Of Massachusetts Branched lipid conjugates of siRNA for specific tissue delivery
US12491255B2 (en) 2019-10-14 2025-12-09 Aro Biotherapeutics Company EPCAM binding fibronectin type III domains
CN114786682B (zh) 2019-10-14 2024-07-16 Aro生物疗法公司 结合cd71的纤维粘连蛋白iii型结构域
WO2021076574A2 (en) 2019-10-14 2021-04-22 Aro Biotherapeutics Company Fn3 domain-sirna conjugates and uses thereof
EP4055165A1 (en) * 2019-11-06 2022-09-14 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases
KR20220110749A (ko) * 2019-11-06 2022-08-09 알닐람 파마슈티칼스 인코포레이티드 간외 전달
CN112876534B (zh) * 2019-11-29 2024-02-09 苏州瑞博生物技术股份有限公司 肝靶向化合物及缀合物
CA3174473A1 (en) * 2020-03-06 2021-09-10 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of transthyretin (ttr)
IL310900A (en) 2020-03-19 2024-04-01 Avidity Biosciences Inc Preparations and methods for the treatment of facial, back and arm muscle atrophy
TW202202173A (zh) 2020-03-27 2022-01-16 美商亞維代堤生物科學公司 治療肌肉萎縮症之組合物及方法
US20230257745A1 (en) 2020-07-10 2023-08-17 Alnylam Pharmaceuticals, Inc. Circular siRNAs
US12329828B2 (en) 2020-09-16 2025-06-17 San Diego State University (Sdsu) Foundation Pyrimidine nucleoside compounds for fluorescence imaging and spectroscopy
CN115516092B (zh) * 2020-09-30 2025-05-16 亿腾医药(苏州)有限公司 血管生成素样3(ANGPTL3)的siRNA及其用途
CR20230308A (es) 2020-12-11 2023-09-08 Civi Biopharma Inc Entrega oral de conjugados antisentido que tienen por blanco a pcsk9
CN114685585B (zh) * 2020-12-31 2024-06-04 苏州瑞博生物技术股份有限公司 核苷酸序列、双链寡核苷酸、药物组合物与缀合物及制备方法和用途
EP4277636A4 (en) * 2021-01-15 2025-11-26 Alnylam Pharmaceuticals Inc MODIFIED OLIGONUCLEOTIDES
US20250283071A1 (en) * 2021-01-22 2025-09-11 Alnylam Pharmaceuticals, Inc. Modified double stranded oligonucleotides
CA3210763A1 (en) 2021-02-12 2022-08-18 Alnylam Pharmaceuticals, Inc. Superoxide dismutase 1 (sod1) irna compositions and methods of use thereof for treating or preventing superoxide dismutase 1- (sod1-) associated neurodegenerative diseases
AU2022231003A1 (en) 2021-03-04 2023-09-14 Alnylam Pharmaceuticals, Inc. Angiopoietin-like 3 (angptl3) irna compositions and methods of use thereof
WO2022189861A1 (en) 2021-03-08 2022-09-15 Tollys Carbohydrate conjugates of tlr3 ligands and uses thereof
KR20230162024A (ko) 2021-03-29 2023-11-28 알닐람 파마슈티칼스 인코포레이티드 헌팅틴(HTT) iRNA 제제 조성물 및 이의 사용 방법
JP2024517610A (ja) 2021-04-14 2024-04-23 アロ・バイオセラピューティクス・カンパニー Cd71に結合するフィブロネクチンiii型ドメイン
US12239710B2 (en) 2021-04-14 2025-03-04 Aro Biotherapeutics Company FN3 domain-siRNA conjugates and uses thereof
AU2022299169A1 (en) 2021-06-23 2024-02-08 Beth Israel Deaconess Medical Center, Inc. Optimized anti-flt1 oligonucleotide compounds for treatment of preeclampsia and other angiogenic disorders
WO2022272108A2 (en) * 2021-06-24 2022-12-29 Sirnaomics, Inc. Products and compositions
EP4367237A2 (en) 2021-07-09 2024-05-15 Alnylam Pharmaceuticals, Inc. Bis-rnai compounds for cns delivery
KR20240036041A (ko) 2021-07-21 2024-03-19 알닐람 파마슈티칼스 인코포레이티드 대사 장애-연관 표적 유전자 iRNA 조성물 및 이의 사용 방법
JP2024530018A (ja) * 2021-08-03 2024-08-14 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 トランスサイレチン(TTR)iRNA組成物およびその使用方法
WO2023043953A1 (en) 2021-09-16 2023-03-23 Avidity Biosciences, Inc. Compositions and methods of treating facioscapulohumeral muscular dystrophy
KR20240067943A (ko) 2021-09-24 2024-05-17 알닐람 파마슈티칼스 인코포레이티드 미소관 연관 단백질 타우(MAPT) iRNA 제제 조성물 및 이의 사용 방법
CA3234887A1 (en) 2021-10-15 2023-04-20 Alnylam Pharmaceuticals, Inc. Extra-hepatic delivery irna compositions and methods of use thereof
US20250223588A1 (en) * 2021-10-19 2025-07-10 Alnylam Pharmaceuticals, Inc. Oligonucleotides with 2'-deoxy-2'-f-2'-c-methyl nucleotides
CN118339294A (zh) * 2021-12-16 2024-07-12 上海拓界生物医药科技有限公司 一种dsRNA、其制备方法及应用
US20250074933A1 (en) * 2022-01-05 2025-03-06 Rona Bioscience, Limited Double-stranded rna having nucleotide analog
US20250188477A1 (en) 2022-03-16 2025-06-12 Daiichi Sankyo Company, Limited CHEMICALLY MODIFIED OLIGONUCLEOTIDE HAVING RNAi ACTIVITY
TW202400787A (zh) 2022-03-16 2024-01-01 美商安彼瑞可股份有限公司 改良siRNA生物可利用性之GalNAc組合物
AU2023234185A1 (en) 2022-03-16 2024-10-03 Daiichi Sankyo Company, Limited siRNA FOR SUPPRESSING EXPRESSION OF TRANSFERRIN RECEPTOR-2
WO2023192830A2 (en) 2022-03-28 2023-10-05 Empirico Inc. Modified oligonucleotides
AU2023356356A1 (en) * 2022-10-07 2025-04-10 Alnylam Pharmaceuticals, Inc. Plasminogen (plg) irna compositions and methods of use thereof
AU2023408479A1 (en) 2022-12-19 2025-05-01 Arnatar Therapeutics, Inc Advanced rna targeting (arnatar)
CN118679174A (zh) 2023-01-20 2024-09-20 石药集团中奇制药技术(石家庄)有限公司 一种经修饰的核苷单体及双链核糖核酸
EP4669750A2 (en) 2023-02-21 2025-12-31 Vib Vzw SYNAPTOGYRIN-3 EXPRESSION INHIBITORS
EP4669749A1 (en) 2023-02-21 2025-12-31 Vib Vzw OLIGONUCLEOTIDES TO MODULATE SYNAPTOGYRIN-3 EXPRESSION
AU2024244071A1 (en) 2023-04-06 2025-10-30 Shanghai Argo Biopharmaceutical Co., Ltd. Nucleoside analog for 5'-phosphonate modification and oligonucleotide prepared therefrom
WO2024229377A1 (en) * 2023-05-03 2024-11-07 Ionis Pharmaceuticals, Inc. Sugar modified oligonucleotides and uses thereof
TW202508607A (zh) * 2023-05-19 2025-03-01 大陸商北京炫景瑞醫藥科技有限公司 雙股寡核苷酸及其共軛物和用途
CN119698475A (zh) 2023-06-13 2025-03-25 昂拓生物医药有限公司 血管紧张素原的高效rna靶向(arnatar)
WO2024263883A2 (en) * 2023-06-22 2024-12-26 The University Of North Carolina At Chapel Hill 5' antisense dna modifications to enhance rna interference activity
WO2025006639A2 (en) 2023-06-27 2025-01-02 Avidity Biosciences, Inc. Compositions and methods of using prkag2-targeting antibody-oligonucleotide conjugates abstract
WO2025007063A1 (en) 2023-06-30 2025-01-02 Avidity Biosciences, Inc. Compositions and methods of using pln-targeting antibody-oligonucleotide conjugates
CN118063533B (zh) * 2023-09-18 2024-08-27 广州必贝特医药股份有限公司 修饰的核苷酸化合物、其寡聚核苷酸及其应用
WO2025064660A2 (en) 2023-09-21 2025-03-27 Alnylam Pharmaceuticals, Inc. Activin a receptor type 1c (acvr1c) irna compositions and methods of use thereof
CN117534717A (zh) * 2024-01-09 2024-02-09 凯莱英生命科学技术(天津)有限公司 5′-(e)-乙烯基磷酸酯的合成方法
EP4665854A1 (en) 2024-01-29 2025-12-24 Arnatar Therapeutics, Inc Translation enhancing nucleic acid compounds: aso coupled translation - upregulation 1 (act-up1) and uses thereof
WO2025165891A1 (en) 2024-01-29 2025-08-07 Arnatar Therapeutics, Inc Translation enhancing nucleic acid compounds: aso coupled translation - upregulation 1 (act-up1) and uses thereof
WO2025196505A2 (en) 2024-03-22 2025-09-25 Takeda Pharmaceutical Company Limited Compositions and methods for inhibiting cytochrome p450 family 7 subfamily a member 1 (cyp7a1) expression

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013532122A (ja) 2010-04-28 2013-08-15 アイシス ファーマシューティカルズ, インコーポレーテッド 修飾ヌクレオシド、その類似体、およびこれらから調製されるオリゴマー化合物
US20130323836A1 (en) 2010-04-22 2013-12-05 Isis Pharmaceuticals, Inc. 5'-end derivatives

Family Cites Families (57)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1861608A (en) 1929-12-21 1932-06-07 Emerson Electric Mfg Co Fan and means for directing the air current therethrough
US1861108A (en) 1930-01-24 1932-05-31 Eugene O Brace Integral clutch and transmission control
US3974808A (en) 1975-07-02 1976-08-17 Ford Motor Company Air intake duct assembly
US4708708A (en) 1982-12-06 1987-11-24 International Paper Company Method and apparatus for skiving and hemming
US4897355A (en) 1985-01-07 1990-01-30 Syntex (U.S.A.) Inc. N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor
US5328470A (en) 1989-03-31 1994-07-12 The Regents Of The University Of Michigan Treatment of diseases by site-specific instillation of cells or site-specific transformation of cells and kits therefor
FR2645866B1 (fr) 1989-04-17 1991-07-05 Centre Nat Rech Scient Nouvelles lipopolyamines, leur preparation et leur emploi
NL8901881A (nl) 1989-07-20 1991-02-18 Rockwool Grodan Bv Drainagekoppelelement.
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
US5283185A (en) 1991-08-28 1994-02-01 University Of Tennessee Research Corporation Method for delivering nucleic acids into cells
WO1993025673A1 (en) 1992-06-04 1993-12-23 The Regents Of The University Of California In vivo gene therapy with intron-free sequence of interest
EP0648265A4 (en) 1992-06-18 1996-12-04 Genpharm Int PROCESS FOR THE PRODUCTION OF NON-HUMAN TRANSGENIC ANIMALS HAVING AN ARTIFICIAL YEAST CHROMOSOME.
EP0833613A1 (en) 1995-05-26 1998-04-08 Somatix Therapy Corporation Delivery vehicles comprising stable lipid/nucleic acid complexes
US6034135A (en) 1997-03-06 2000-03-07 Promega Biosciences, Inc. Dimeric cationic lipids
US8273866B2 (en) * 2002-02-20 2012-09-25 Merck Sharp & Dohme Corp. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (SINA)
EP2530157B1 (en) * 2003-07-31 2016-09-28 Regulus Therapeutics Inc. Oligomeric compounds and compositions for use in modulation of miRNAs
ATE452188T1 (de) 2004-02-10 2010-01-15 Sirna Therapeutics Inc Rna-interferenz-vermittelte hemmung der genexpression unter verwendung multifunktioneller sina (short interfering nucleic acid)
CH698304B1 (de) 2005-10-10 2009-07-15 Fatzer Ag Drahtseilanker, insbesondere für Steinschlag- oder Lawinenschutzverbauungen.
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
EP1989307B1 (en) 2006-02-08 2012-08-08 Quark Pharmaceuticals, Inc. NOVEL TANDEM siRNAS
KR101221589B1 (ko) 2006-04-07 2013-01-15 이데라 파마슈티칼즈, 인코포레이티드 Tlr7 및 tlr8에 대한 안정화된 면역 조절성 rna〔simra〕 화합물
US8324179B2 (en) 2007-02-09 2012-12-04 Gilead Sciences, Inc. Nucleoside analogs for antiviral treatment
EP2357231A2 (en) 2007-07-09 2011-08-17 Idera Pharmaceuticals, Inc. Stabilized immune modulatory RNA (SIMRA) compounds
CA2715289C (en) * 2008-02-11 2019-12-24 Rxi Pharmaceuticals Corporation Modified rnai polynucleotides and uses thereof
EP2321414B1 (en) 2008-07-25 2018-01-10 Alnylam Pharmaceuticals, Inc. Enhancement of sirna silencing activity using universal bases or mismatches in the sense strand
US20100183704A1 (en) * 2008-09-25 2010-07-22 Novartis Ag dsRNA FOR TREATING VIRAL INFECTION
WO2010141511A2 (en) 2009-06-01 2010-12-09 Halo-Bio Rnai Therapeutics, Inc. Polynucleotides for multivalent rna interference, compositions and methods of use thereof
DK2470656T3 (da) 2009-08-27 2015-06-22 Idera Pharmaceuticals Inc Sammensætning til hæmning af genekspression og anvendelser heraf
WO2011109427A2 (en) 2010-03-01 2011-09-09 Alnylam Pharmaceuticals, Inc. Improving the biological activity of sirna through modulation of its thermodynamic profile
WO2011133876A2 (en) * 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising acyclic and abasic nucleosides and analogs
KR102481317B1 (ko) 2011-03-29 2022-12-26 알닐람 파마슈티칼스 인코포레이티드 Tmprss6 유전자의 발현을 억제하기 위한 조성물 및 방법
CN107201364A (zh) 2011-06-21 2017-09-26 阿尔尼拉姆医药品有限公司 用于抑制载脂蛋白c‑iii(apoc3)基因表达的组合物与方法
US9228188B2 (en) 2011-06-21 2016-01-05 Alnylam Pharmaceuticals, Inc. Compositions and method for inhibiting hepcidin antimicrobial peptide (HAMP) or HAMP-related gene expression
WO2012177949A2 (en) 2011-06-21 2012-12-27 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibition of expression of protein c (proc) genes
MX345095B (es) 2011-06-21 2017-01-17 Alnylam Pharmaceuticals Inc Composiciones de arni similares a angiopoyetina 3 (angptl3) y metodos para su uso.
EP3597750B1 (en) 2011-06-23 2022-05-04 Alnylam Pharmaceuticals, Inc. Serpina1 sirnas: compositions of matter and methods of treatment
US9399775B2 (en) * 2011-11-18 2016-07-26 Alnylam Pharmaceuticals, Inc. RNAi agents, compositions and methods of use thereof for treating transthyretin (TTR) associated diseases
SI3366775T2 (sl) * 2011-11-18 2025-12-31 Alnylam Pharmaceuticals, Inc. Modificirana sredstva RNAI
US9133461B2 (en) 2012-04-10 2015-09-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the ALAS1 gene
US9127274B2 (en) 2012-04-26 2015-09-08 Alnylam Pharmaceuticals, Inc. Serpinc1 iRNA compositions and methods of use thereof
EP4253395A3 (en) * 2012-08-06 2023-11-29 Alnylam Pharmaceuticals, Inc. Processes for the preparation of carbohydrate conjugated rna agents
CA2880290C (en) 2012-09-12 2020-10-27 Quark Pharmaceuticals, Inc. Double-stranded oligonucleotide molecules targeting p53 and methods of use thereof
AU2013315524B2 (en) * 2012-09-12 2019-01-31 Quark Pharmaceuticals, Inc. Double-stranded oligonucleotide molecules to p53 and methods of use thereof
PT2929031T (pt) * 2012-12-05 2018-01-19 Alnylam Pharmaceuticals Inc Composições de irna de pcsk9 e métodos de seu uso
CN105324485B (zh) 2013-03-14 2021-11-23 阿尔尼拉姆医药品有限公司 补体组分C5 iRNA组合物及其使用方法
MY181888A (en) 2013-05-22 2021-01-12 Alnylam Pharmaceuticals Inc Tmprss6 irna compositions and methods of use thereof
KR102295648B1 (ko) 2013-05-22 2021-08-31 알닐람 파마슈티칼스 인코포레이티드 SERPINA1 iRNA 조성물 및 이의 사용 방법
WO2015042564A1 (en) 2013-09-23 2015-03-26 Alnylam Pharmaceuticals, Inc. Methods for treating or preventing transthyretin (ttr) associated diseases
CA2925107A1 (en) 2013-10-02 2015-04-09 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the lect2 gene
ES2804510T3 (es) 2013-10-04 2021-02-08 Alnylam Pharmaceuticals Inc Composiciones y métodos para inhibir la expresión del gen ALAS1
EP3065783A4 (en) * 2013-11-06 2017-06-21 Merck Sharp & Dohme Corp. Dual molecular delivery of oligonucleotides and peptide containing conjugates
IL314045A (en) 2013-12-12 2024-09-01 Alnylam Pharmaceuticals Inc Complement component irna compositions and methods of use thereof
JP6594902B2 (ja) 2014-02-11 2019-10-23 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 ケトヘキソキナーゼ(KHK)iRNA組成物及びその使用方法
SG10202104570TA (en) 2014-05-22 2021-06-29 Alnylam Pharmaceuticals Inc Angiotensinogen (agt) irna compositions and methods of use thereof
IL316808A (en) 2014-08-20 2025-01-01 Alnylam Pharmaceuticals Inc Modified double-stranded RNA materials and their uses
KR102054401B1 (ko) 2018-03-26 2019-12-10 주식회사 엔지켐생명과학 1,2-디아실글리세롤 화합물, 그 제조방법 및 이를 유효성분으로 함유하는 면역조절제
KR102318555B1 (ko) 2020-03-19 2021-10-29 한국과학기술연구원 광소자용 역나노콘과 그 제조방법

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130323836A1 (en) 2010-04-22 2013-12-05 Isis Pharmaceuticals, Inc. 5'-end derivatives
JP2013532122A (ja) 2010-04-28 2013-08-15 アイシス ファーマシューティカルズ, インコーポレーテッド 修飾ヌクレオシド、その類似体、およびこれらから調製されるオリゴマー化合物

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Mol. BioSyst., 2010, Vol.6, p.862-870
Nucleic Acids Research, 2003, Vol.31(2), p.589-595
The FASEB Journal, 2013, Vol.27, p.4017-4026

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