[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

EA201790420A1 - Средства, представляющие собой модифицированную двухнитевую рнк - Google Patents

Средства, представляющие собой модифицированную двухнитевую рнк

Info

Publication number
EA201790420A1
EA201790420A1 EA201790420A EA201790420A EA201790420A1 EA 201790420 A1 EA201790420 A1 EA 201790420A1 EA 201790420 A EA201790420 A EA 201790420A EA 201790420 A EA201790420 A EA 201790420A EA 201790420 A1 EA201790420 A1 EA 201790420A1
Authority
EA
Eurasian Patent Office
Prior art keywords
nucleotide
nucleotides
modification
dsrna
suppressing
Prior art date
Application number
EA201790420A
Other languages
English (en)
Inventor
Мартин Майер
Дон Фостер
Стюарт Милстейн
Сатия Кучиманчи
Васант Джадхав
Каллантхоттатхил Раджив
Мутхиах Манохаран
Рубина Пармар
Original Assignee
Элнилэм Фармасьютикалз, Инк.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Элнилэм Фармасьютикалз, Инк. filed Critical Элнилэм Фармасьютикалз, Инк.
Publication of EA201790420A1 publication Critical patent/EA201790420A1/ru

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/313—Phosphorodithioates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/322—2'-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C12N2310/332—Abasic residue
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C12N2310/335—Modified T or U
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/344—Position-specific modifications, e.g. on every purine, at the 3'-end
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/50—Physical structure
    • C12N2310/53—Physical structure partially self-complementary or closed
    • C12N2310/533—Physical structure partially self-complementary or closed having a mismatch or nick in at least one of the strands
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/50—Methods for regulating/modulating their activity
    • C12N2320/51—Methods for regulating/modulating their activity modulating the chemical stability, e.g. nuclease-resistance
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/50—Methods for regulating/modulating their activity
    • C12N2320/52—Methods for regulating/modulating their activity modulating the physical stability, e.g. GC-content

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Abstract

Один аспект настоящего изобретения относится к средству, представляющему собой двухнитевую РНК (dsRNA), способному подавлять экспрессию целевого гена. Смысловая нить средства, представляющего собой dsRNA, содержит по меньшей мере один нарушающий термостабильность нуклеотид, при этом по меньшей мере один указанный нарушающий термостабильность нуклеотид встречается в сайте, противоположном затравочному участку (положения 2-8) антисмысловой нити; а антисмысловая нить средства, представляющего собой dsRNA, содержит по меньшей мере два нуклеотида с модификацией, придающей нуклеотиду стерический объем, который меньше стерического объема 2'-ОМе-модификации или равен ему, где указанные нуклеотиды с модификацией разделены участком длиной 11 нуклеотидов. Другие аспекты настоящего изобретения относятся к фармацевтическим композициям, содержащим эти средства, представляющие собой dsRNA, подходящие для применения в терапевтических целях, и к способам подавления экспрессии целевого гена путем введения этих средств, представляющих собой dsRNA, например, для лечения различных патологических состояний.
EA201790420A 2014-08-20 2015-08-14 Средства, представляющие собой модифицированную двухнитевую рнк EA201790420A1 (ru)

Applications Claiming Priority (4)

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

Publications (1)

Publication Number Publication Date
EA201790420A1 true EA201790420A1 (ru) 2017-07-31

Family

ID=53969461

Family Applications (1)

Application Number Title Priority Date Filing Date
EA201790420A EA201790420A1 (ru) 2014-08-20 2015-08-14 Средства, представляющие собой модифицированную двухнитевую рнк

Country Status (12)

Country Link
US (11) US10233448B2 (ru)
EP (3) EP3812462A1 (ru)
JP (4) JP7289610B2 (ru)
KR (3) KR102630289B1 (ru)
CN (3) CN118652888A (ru)
CA (1) CA2958758A1 (ru)
EA (1) EA201790420A1 (ru)
IL (3) IL316808A (ru)
MX (3) MX2017002144A (ru)
NZ (1) NZ730296A (ru)
SG (3) SG10201903290YA (ru)
WO (1) WO2016028649A1 (ru)

Families Citing this family (115)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX345095B (es) 2011-06-21 2017-01-17 Alnylam Pharmaceuticals Inc Composiciones de arni similares a angiopoyetina 3 (angptl3) y metodos para su uso.
KR102534909B1 (ko) * 2011-11-18 2023-05-30 알닐람 파마슈티칼스 인코포레이티드 변형된 ＲＮＡｉ 제제
KR102712879B1 (ko) 2012-07-13 2024-10-04 웨이브 라이프 사이언시스 리미티드 키랄 제어
KR102463973B1 (ko) 2013-05-22 2022-11-07 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
EP3221451A1 (en) * 2014-11-17 2017-09-27 Alnylam Pharmaceuticals, Inc. Apolipoprotein c3 (apoc3) irna compositions and methods of use thereof
US20160319278A1 (en) 2015-04-03 2016-11-03 University Of Massachusetts Fully stabilized asymmetric sirna
EP3283631A1 (en) * 2015-04-13 2018-02-21 Alnylam Pharmaceuticals, Inc. Angiopoietin-like 3 (angptl3) irna compositions and methods of use thereof
MY195720A (en) 2015-07-31 2023-02-07 Alnylam Pharmaceuticals Inc Transthyretin (Ttr) Irna Compositions and Methods of Use Thereof for Treating or Preventing Ttr-Associated Diseases
US10633653B2 (en) 2015-08-14 2020-04-28 University Of Massachusetts Bioactive conjugates for oligonucleotide delivery
EP3408391A4 (en) 2016-01-31 2019-08-28 University of Massachusetts BRANCHED OLIGONUCLEOTIDES
CA3012700A1 (en) * 2016-02-01 2017-08-10 Arrakis Therapeutics, Inc. Compounds and methods of treating rna-mediated diseases
MA45470A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Acides nucléiques kras et leurs utilisations
MA45469A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Acides nucléiques de bêta-caténine et leurs utilisations
MA45328A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Compositions acide nucléique-polypeptide et utilisations de celles-ci
MA45349A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Acides nucléiques egfr et leurs utilisations
CN109526222B (zh) 2016-06-06 2022-04-29 箭头药业股份有限公司 5’-环膦酸酯修饰核苷酸
EP3496758A4 (en) 2016-08-12 2020-11-11 University of Massachusetts CONJUGATE OLIGONUCLEOTIDES
CA3033867A1 (en) * 2016-08-17 2018-02-22 Solstice Biologics, Ltd. Polynucleotide constructs
MX2019005149A (es) * 2016-11-07 2019-06-24 nanoSUR LLC Arn bicatenario con modificaciones quimicas postranscripcionales.
WO2018089582A1 (en) 2016-11-10 2018-05-17 San Diego State University Research Foundation Compounds for fluorescence sensing of duplex formation
TW202313978A (zh) * 2016-11-23 2023-04-01 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
US11504391B1 (en) * 2016-11-23 2022-11-22 Alnylam Pharmaceuticals, Inc. Modified RNA agents with reduced off-target effect
AU2017378226A1 (en) 2016-12-14 2019-06-20 Janssen Biotech, Inc. CD8A-binding fibronectin type III domains
US10611823B2 (en) 2016-12-14 2020-04-07 Hanssen Biotech, Inc CD137 binding fibronectin type III domains
SG10201913552UA (en) * 2016-12-16 2020-03-30 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
EP3550022A1 (en) * 2018-04-05 2019-10-09 Silence Therapeutics GmbH Products and compositions
US11174483B2 (en) * 2017-04-05 2021-11-16 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
EP3681513A4 (en) 2017-09-14 2021-09-22 Arrowhead Pharmaceuticals, Inc. RNAI AGENTS AND COMPOSITIONS FOR INHIBITED ANALOGUE EXPRESSION OF ANGIOPOIETIN 3 (ANGPTL3) AND METHODS FOR USE
BR112020005230A2 (pt) 2017-09-19 2020-09-24 Alnylam Pharmaceuticals, Inc. composições e métodos para o tratamento da amiloidose mediada por transtiretina (ttr)
CN111655268B (zh) * 2017-10-04 2024-03-26 艾维迪提生物科学公司 核酸-多肽组合物及其用途
AU2018363837B2 (en) * 2017-11-13 2024-11-14 Silence Therapeutics Gmbh Nucleic acids for inhibiting expression of a target gene comprising phosphorodithioate linkages
CA3078540A1 (en) 2017-11-30 2019-06-06 Arrakis Therapeutics, Inc. Nucleic acid-binding photoprobes and uses thereof
WO2019105404A1 (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
AU2018374219C1 (en) * 2017-12-01 2023-05-11 Suzhou Ribo Life Science Co., Ltd. Double-stranded oligonucleotide, composition and conjugate comprising double-stranded oligonucleotide, preparation method therefor and use thereof
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
WO2019105435A1 (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
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
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
AU2018377716B2 (en) 2017-12-01 2024-12-19 Suzhou Ribo Life Science Co., Ltd Nucleic acid, composition and conjugate comprising the same, and preparation method and use thereof
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
EP3677588A4 (en) * 2017-12-26 2020-11-25 Guangzhou Ribobio Co., Ltd. MODIFIED OLIGONUCLEOTIDES AND COMPOUND WHICH CAN BE USED FOR THE SYNTHESIS OF THEM
AU2018394875B2 (en) 2017-12-29 2023-08-03 Suzhou Ribo Life Science Co., Ltd. Conjugates and preparation and use thereof
WO2019168686A1 (en) * 2018-03-02 2019-09-06 Dicerna Pharmaceuticals, Inc. Methods and compositions for treating bile duct paucity-associated conditions
US20210155926A1 (en) * 2018-04-05 2021-05-27 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
EP3790557A4 (en) * 2018-05-07 2022-03-02 Alnylam Pharmaceuticals Inc. COMPOSITIONS AND METHODS FOR ENHANCING STRAND DISTORTION
JP7353301B2 (ja) 2018-05-07 2023-09-29 アルニラム ファーマスーティカルズ インコーポレイテッド 肝臓外送達
EP3802827A4 (en) * 2018-05-16 2022-08-03 Alnylam Pharmaceuticals, Inc. MODIFIED RNA AGENTS WITH REDUCED OFF-TARGET EFFECT
US11918600B2 (en) 2018-08-21 2024-03-05 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition and conjugate containing nucleic acid, and use thereof
JP7627042B2 (ja) * 2018-08-23 2025-02-05 ユニバーシティー オブ マサチューセッツ Ｏ－メチルリッチ完全安定化オリゴヌクレオチド
CA3114396A1 (en) * 2018-09-28 2020-04-02 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases
WO2020063198A1 (zh) 2018-09-30 2020-04-02 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
EP3877524A4 (en) * 2018-11-09 2023-10-11 Alnylam Pharmaceuticals Inc. MODIFIED DOUBLE-STRANDED OLIGONUCLEOTIDES
AU2019395341A1 (en) * 2018-12-10 2021-06-17 Amgen Inc. Chemically-modified RNAi constructs and uses thereof
CA3124090A1 (en) * 2018-12-19 2020-06-25 Alnylam Pharmaceuticals, Inc. Amyloid precursor protein (app) rnai agent compositions and methods of 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
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
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
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
WO2020135673A1 (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
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
US11492619B2 (en) 2019-01-18 2022-11-08 University Of Massachusetts Dynamic pharmacokinetic-modifying anchors
WO2020147847A1 (zh) * 2019-01-18 2020-07-23 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
EP3974532A4 (en) * 2019-05-22 2024-01-24 Suzhou Ribo Life Science Co., Ltd. NUCLEIC ACID, PHARMACEUTICAL COMPOSITION, CONJUGATE, PROCESS OF PREPARATION AND USE
US20230313195A1 (en) * 2019-05-22 2023-10-05 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition, conjugate, preparation method, 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
US20220315929A1 (en) * 2019-05-24 2022-10-06 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition and conjugate, preparation method therefor and use thereof
KR20220012284A (ko) * 2019-05-24 2022-02-03 쑤저우 리보 라이프 사이언스 컴퍼니, 리미티드 핵산, 약학 조성물, 컨쥬게이트와 이의 제조 방법 및 용도
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
JP2022538404A (ja) * 2019-06-21 2022-09-02 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 構造的に明確なｓｉＲＮＡ－二重可変ドメイン免疫グロブリンコンジュゲート
AU2020329155A1 (en) 2019-08-09 2022-03-10 University Of Massachusetts Chemically modified oligonucleotides targeting SNPs
KR20220062517A (ko) 2019-08-15 2022-05-17 아이오니스 파마수티컬즈, 인코포레이티드 결합 변형된 올리고머 화합물 및 이의 용도
US11781138B2 (en) 2019-10-14 2023-10-10 Aro Biotherapeutics Company FN3 domain-siRNA conjugates and uses thereof
WO2021076546A1 (en) 2019-10-14 2021-04-22 Aro Biotherapeutics Company Cd71 binding fibronectin type iii domains
WO2021092145A1 (en) * 2019-11-06 2021-05-14 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna composition 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
EP4114949A1 (en) * 2020-03-06 2023-01-11 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of transthyretin (ttr)
KR20220156867A (ko) 2020-03-19 2022-11-28 어비디티 바이오사이언시스 인크. 안면견갑상완 근이영양증의 치료용 조성물 및 방법
US20230257745A1 (en) 2020-07-10 2023-08-17 Alnylam Pharmaceuticals, Inc. Circular siRNAs
CN116333013A (zh) * 2020-09-30 2023-06-27 纳肽得(青岛)生物医药有限公司 一种靶向配体
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
US20240116973A1 (en) * 2021-01-15 2024-04-11 Alnylam Pharmaceuticals, Inc. Modified oligonucleotides
MX2023008469A (es) * 2021-01-22 2023-11-22 Alnylam Pharmaceuticals Inc Oligonucleotidos de doble hebra modificados.
KR20230146048A (ko) 2021-02-12 2023-10-18 알닐람 파마슈티칼스 인코포레이티드 슈퍼옥사이드 디스뮤타제 1(sod1) irna 조성물 및 슈퍼옥사이드 디스뮤타제 1- (sod1-) 관련 신경퇴행성 질환을 치료하거나 예방하기 위한 이의 사용 방법
MX2023010249A (es) 2021-03-04 2023-09-15 Alnylam Pharmaceuticals Inc Composiciones de arni de proteina similar a la angiopoyetina 3 (angptl3) y metodos para usarlas.
WO2022189861A1 (en) 2021-03-08 2022-09-15 Tollys Carbohydrate conjugates of tlr3 ligands and uses thereof
MX2023011466A (es) 2021-03-29 2024-02-01 Alnylam Pharmaceuticals Inc Composiciones de agentes de ácido ribonucleico de interferencia (arni) de huntingtina (htt) y métodos de uso de estas.
MX2023012128A (es) 2021-04-14 2024-01-11 Aro Biotherapeutics Company Dominios tipo iii de la fibronectina que se unen a cd71.
CN117677699A (zh) 2021-06-23 2024-03-08 马萨诸塞大学 用于治疗先兆子痫和其他血管生成病症的优化抗flt1寡核苷酸化合物
EP4359540A2 (en) * 2021-06-24 2024-05-01 Sirnaomics, Inc. Products and compositions
JP2024527584A (ja) 2021-07-09 2024-07-25 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 ＣＮＳ送達のためのＢｉｓ－ＲＮＡｉ化合物
TW202421169A (zh) 2021-07-21 2024-06-01 美商艾拉倫製藥股份有限公司 代謝疾患相關的標靶基因ｉＲＮＡ組成物及其使用方法
CN117795074A (zh) 2021-08-03 2024-03-29 阿尔尼拉姆医药品有限公司 转甲状腺素蛋白（TTR）iRNA组合物和其使用方法
WO2023043953A1 (en) 2021-09-16 2023-03-23 Avidity Biosciences, Inc. Compositions and methods of treating facioscapulohumeral muscular dystrophy
AU2022364838A1 (en) 2021-10-15 2024-04-11 Alnylam Pharmaceuticals, Inc. Extra-hepatic delivery irna compositions and methods of use thereof
JP2024539093A (ja) * 2021-10-19 2024-10-28 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 ２’－デオキシ－２’－ｆ－２’－ｃ－メチルヌクレオチドを有するオリゴヌクレオチド
WO2023109932A1 (zh) * 2021-12-16 2023-06-22 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
CN116003494B (zh) * 2022-01-05 2024-11-12 大睿生物医药科技(上海)有限公司 核苷酸双聚体及包含其的双链rna
AU2023234536A1 (en) 2022-03-16 2024-09-26 Empirico Inc. Galnac compositions for improving sirna bioavailability
TW202400786A (zh) 2022-03-16 2024-01-01 日商第一三共股份有限公司 具有RNAi活性的化學修飾寡核苷酸
JPWO2023176862A1 (ru) 2022-03-16 2023-09-21
WO2024077148A1 (en) * 2022-10-07 2024-04-11 Alnylam Pharmaceuticals, Inc. Plasminogen (plg) irna compositions and methods of use thereof
WO2024175588A1 (en) 2023-02-21 2024-08-29 Vib Vzw Oligonucleotides for modulating synaptogyrin-3 expression
WO2024175586A2 (en) 2023-02-21 2024-08-29 Vib Vzw Inhibitors of synaptogyrin-3 expression
WO2024229377A1 (en) * 2023-05-03 2024-11-07 Ionis Pharmaceuticals, Inc. Sugar modified oligonucleotides and uses thereof
WO2024240080A1 (zh) * 2023-05-19 2024-11-28 北京炫景瑞医药科技有限公司 双链寡核苷酸及其缀合物和用途
WO2024259134A1 (en) 2023-06-13 2024-12-19 Arnatar Therapeutics, Inc Advanced rna targeting (arnatar) for angiotensinogen
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
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

Family Cites Families (59)

* 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
JP3285355B2 (ja) 1992-06-04 2002-05-27 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア ｉｎｖｉｖｏ遺伝子治療のための方法及び組成物
WO1994000569A1 (en) 1992-06-18 1994-01-06 Genpharm International, Inc. Methods for producing transgenic non-human animals harboring a yeast artificial chromosome
WO1996037194A1 (en) 1995-05-26 1996-11-28 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)
WO2005078097A2 (en) 2004-02-10 2005-08-25 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING MULTIFUNCTIONAL SHORT INTERFERING NUCLEIC ACID (Multifunctional siNA)
EP2530157B1 (en) * 2003-07-31 2016-09-28 Regulus Therapeutics Inc. Oligomeric compounds and compositions for use in modulation of miRNAs
CH698304B1 (de) 2005-10-10 2009-07-15 Fatzer Ag Drahtseilanker, insbesondere für Steinschlag- oder Lawinenschutzverbauungen.
AU2006308765B2 (en) * 2005-11-02 2013-09-05 Arbutus Biopharma Corporation Modified siRNA molecules and uses thereof
EP1989307B1 (en) 2006-02-08 2012-08-08 Quark Pharmaceuticals, Inc. NOVEL TANDEM siRNAS
CA2648585C (en) 2006-04-07 2017-07-25 Idera Pharmaceuticals, Inc. Stabilized immune modulatory rna (simra) compounds for tlr7 and tlr8
WO2008100447A2 (en) 2007-02-09 2008-08-21 Gilead Sciences, Inc. Nucleoside analogs for antiviral treatment
AU2008279509B2 (en) 2007-07-09 2011-07-21 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
AU2009273878A1 (en) 2008-07-25 2010-01-28 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
EP2438168B1 (en) 2009-06-01 2020-02-12 Halo-Bio Rnai Therapeutics, Inc. Polynucleotides for multivalent rna interference, compositions and methods of use thereof
US8431544B1 (en) 2009-08-27 2013-04-30 Idera Pharmaceuticals, Inc. Compositions for inhibiting gene expression and uses thereof
WO2011109427A2 (en) * 2010-03-01 2011-09-09 Alnylam Pharmaceuticals, Inc. Improving the biological activity of sirna through modulation of its thermodynamic profile
US10913767B2 (en) 2010-04-22 2021-02-09 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising acyclic and abasic nucleosides and analogs
US9725479B2 (en) * 2010-04-22 2017-08-08 Ionis Pharmaceuticals, Inc. 5′-end derivatives
US8993738B2 (en) 2010-04-28 2015-03-31 Isis Pharmaceuticals, Inc. Modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom
CN113736782B (zh) 2011-03-29 2024-07-16 阿尔尼拉姆医药品有限公司 用于抑制tmprss6基因表达的组合物和方法
WO2012177921A2 (en) 2011-06-21 2012-12-27 Alnylam Pharmaceuticals, Inc Compositions and methods for inhibiting hepcidin antimicrobial peptide (hamp) or hamp-related gene expression
MX345095B (es) 2011-06-21 2017-01-17 Alnylam Pharmaceuticals Inc Composiciones de arni similares a angiopoyetina 3 (angptl3) y metodos para su uso.
US9068184B2 (en) 2011-06-21 2015-06-30 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibition of expression of protein C (PROC) genes
MX344807B (es) 2011-06-21 2017-01-09 Alnylam Pharmaceuticals Inc Composiciones y metodos para inhibicion de genes para alipoproteina c-iii (apoc3).
US20140235693A1 (en) 2011-06-23 2014-08-21 Alnylam Pharmaceuticals, Inc. Serpina1 sirnas: compositions of matter and methods of treatment
KR102534909B1 (ko) * 2011-11-18 2023-05-30 알닐람 파마슈티칼스 인코포레이티드 변형된 ＲＮＡｉ 제제
KR102095699B1 (ko) 2011-11-18 2020-04-02 알닐람 파마슈티칼스 인코포레이티드 트랜스티레틴（ＴＴＲ） 관련 질병을 치료하기 위한 ＲＮＡｉ 제제, 조성 및 그의 사용방법
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
ES2947520T3 (es) 2012-08-06 2023-08-10 Alnylam Pharmaceuticals Inc Proceso para la preparación de agentes de ARN conjugados con carbohidratos
CN104619844A (zh) * 2012-09-12 2015-05-13 夸克制药公司 靶向p53的双链寡核苷酸分子及其使用方法
WO2014043292A1 (en) * 2012-09-12 2014-03-20 Quark Pharmaceuticals, Inc. Double-stranded oligonucleotide molecules to p53 and methods of use thereof
CN104854242B (zh) * 2012-12-05 2018-03-16 阿尔尼拉姆医药品有限公司 PCSK9 iRNA组合物及其使用方法
IL288931B1 (en) 2013-03-14 2025-01-01 Alnylam Pharmaceuticals Inc Compositions comprising a complementary portion of C5 IRNA and methods of using them
BR112015029276B1 (pt) 2013-05-22 2022-07-12 Alnylam Pharmaceuticals, Inc Agente de irna fita dupla capaz de inibir a expressão de tmprss6, composição farmacêutica e uso dos mesmos
KR102463973B1 (ko) 2013-05-22 2022-11-07 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
MX2016004230A (es) 2013-10-02 2016-10-21 Alnylam Pharmaceuticals Inc Composiciones y metodos para inhibir la expresion del gen lect2.
BR122020001264B1 (pt) 2013-10-04 2022-11-22 Icahn School Of Medicine At Mount Sinai Ácido ribonucleico de fita dupla (dsrna) para inibição da expressão de alas1, composição farmacêutica para inibição da expressão de um gene alas1, métodos de inibição da expressão de alas1 em uma célula e para diminuir um nível de uma porfirina ou de um precursor de porfirina em uma célula, usos de um dsrna, método para avaliar o nível de mrna de alas1 extracelular em circulação em um indivíduo, composição e uso da mesma
EP3065783A4 (en) * 2013-11-06 2017-06-21 Merck Sharp & Dohme Corp. Dual molecular delivery of oligonucleotides and peptide containing conjugates
CA2931090A1 (en) 2013-12-12 2015-06-18 Alnylam Pharmaceuticals, Inc. Complement component irna compositions and methods of use thereof
EP3960860A3 (en) 2014-02-11 2022-06-08 Alnylam Pharmaceuticals, Inc. Ketohexokinase (khk) irna compositions and methods of use thereof
CN112852809A (zh) 2014-05-22 2021-05-28 阿尔尼拉姆医药品有限公司 血管紧张素原(AGT)iRNA组合物及其使用方法
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

Also Published As

Publication number Publication date
MX2024005652A (es) 2024-05-28
IL250448A0 (en) 2017-03-30
US20240409942A1 (en) 2024-12-12
US11549109B2 (en) 2023-01-10
US20220002727A1 (en) 2022-01-06
JP2021073183A (ja) 2021-05-13
JP2021073182A (ja) 2021-05-13
KR20170099832A (ko) 2017-09-01
US20230183701A1 (en) 2023-06-15
EP3812462A1 (en) 2021-04-28
KR20230019498A (ko) 2023-02-08
IL280941A (en) 2021-04-29
US10233448B2 (en) 2019-03-19
US20220389424A1 (en) 2022-12-08
CN114181942A (zh) 2022-03-15
SG11201701166UA (en) 2017-03-30
US20220056448A1 (en) 2022-02-24
CN118652888A (zh) 2024-09-17
MX2024005653A (es) 2024-05-28
SG10201913791QA (en) 2020-03-30
IL316808A (en) 2025-01-01
EP3186377A1 (en) 2017-07-05
NZ730296A (en) 2023-09-29
US11427822B2 (en) 2022-08-30
MX2017002144A (es) 2017-08-15
KR102494171B1 (ko) 2023-02-02
JP7289610B2 (ja) 2023-06-12
US20210017519A1 (en) 2021-01-21
US12168767B2 (en) 2024-12-17
IL280941B1 (en) 2024-12-01
JP2024020209A (ja) 2024-02-14
JP2017525705A (ja) 2017-09-07
US20190241891A1 (en) 2019-08-08
KR20240010762A (ko) 2024-01-24
SG10201903290YA (en) 2019-05-30
US20250034572A1 (en) 2025-01-30
IL250448B (en) 2021-03-25
WO2016028649A1 (en) 2016-02-25
EP3808846A1 (en) 2021-04-21
US20190241893A1 (en) 2019-08-08
US20230110876A1 (en) 2023-04-13
US10612024B2 (en) 2020-04-07
NZ767118A (en) 2024-02-23
US10612027B2 (en) 2020-04-07
KR102630289B1 (ko) 2024-01-31
US11401517B2 (en) 2022-08-02
JP7370311B2 (ja) 2023-10-27
CA2958758A1 (en) 2016-02-25
US20170275626A1 (en) 2017-09-28
CN107075516A (zh) 2017-08-18

Similar Documents

Publication Publication Date Title
EA201790420A1 (ru) Средства, представляющие собой модифицированную двухнитевую рнк
MX2023010958A (es) Agentes de arn modificados con efecto reducido fuera de la diana.
WO2015106128A3 (en) Rnai agents modified at the 4'-c-position
MX2021006745A (es) Constructos de iarn modificados quimicamente y usos de estos.
EA201490993A1 (ru) МОДИФИЦИРОВАННЫЕ СРЕДСТВА РНКи
MX2018006989A (es) Metodos y composiciones para el tratamiento contra un trastorno asociado a serpinc1.
EA201390230A1 (ru) Замещенные аналоги нуклеотидов
SA519401379B1 (ar) علاج فيروس مرتبط بغدة لمرض هنتنجتون
EA201591707A1 (ru) КОМПОЗИЦИИ иРНК КОМПОНЕНТА КОМПЛЕМЕНТА C5 И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
WO2014022739A3 (en) Modified rnai agents
WO2016106401A3 (en) Rna agents for p21 gene modulation
EA201490042A1 (ru) Азетидинил-фенил-, пиридил- или пиразинилкарбоксамидные производные как ингибиторы jak
EA201690526A1 (ru) Замещенные нуклеозиды, нуклеотиды и их аналоги
EA201590850A1 (ru) Трициклические конденсированные производные тиофена как ингибиторы jak
EA201791874A1 (ru) Фторированные ингибиторы лизилоксидазоподобного фермента-2 и их применение
EA201890592A1 (ru) Жидкие фармацевтические композиции, содержащие ингибиторы sglt-2
WO2019217397A3 (en) Compositions and methods for improving strand biased
EA202090720A1 (ru) ПРОИЗВОДНЫЕ GalNAc
MX2016007980A (es) Acido nucleico que induce acido ribonucleico de interferencia modificado para prevenir una falla en alcanzar el objetivo, y uso del mismo.
MX2022001017A (es) Composiciones y metodos para inhibir la expresion del gen de sintasa de acido 5'-aminolevulinico 1 (alas1).
MX2021007001A (es) Moleculas inhibidoras de acido nucleico de cadena doble que contienen un tribucle.
EA201892366A1 (ru) Антисмысловые олигомеры и способы их применения для лечения заболеваний, связанных с геном кислой альфа-глюкозидазы
WO2017007886A3 (en) Compositions for inhibiting dux4 gene expression and uses thereof
WO2016183009A3 (en) Methods and compositions for the specific inhibition of antithrombin 3 (at3) by double-stranded rna
MX2023008469A (es) Oligonucleotidos de doble hebra modificados.