CA2856289A1 - Modified rnai agents - Google Patents

Modified rnai agents Download PDF

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Publication number
CA2856289A1
CA2856289A1 CA2856289A CA2856289A CA2856289A1 CA 2856289 A1 CA2856289 A1 CA 2856289A1 CA 2856289 A CA2856289 A CA 2856289A CA 2856289 A CA2856289 A CA 2856289A CA 2856289 A1 CA2856289 A1 CA 2856289A1
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CA
Canada
Prior art keywords
nucleotides
double
strand
rnai agent
stranded rnai
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
CA2856289A
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English (en)
French (fr)
Inventor
Kallanthottathil G. Rajeev
Tracy Zimmermann
Muthiah Manoharan
Martin Maier
Satyanarayana Kuchimanchi
Klaus CHARISSE
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alnylam Pharmaceuticals Inc
Original Assignee
Alnylam Pharmaceuticals Inc
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=47295193&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2856289(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Alnylam Pharmaceuticals Inc filed Critical Alnylam Pharmaceuticals Inc
Publication of CA2856289A1 publication Critical patent/CA2856289A1/en
Pending legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • 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
    • A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • 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 nucleic acids [NA]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
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    • 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
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    • 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
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • 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
    • C12N2310/343—Spatial arrangement of the modifications having patterns, e.g. ==--==--==--
    • 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
    • C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
    • C12N2310/3521—Methyl
    • 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
    • C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon
    • C12N2310/3533—Halogen
    • 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
    • C12N2320/30—Special therapeutic applications
    • 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

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Virology (AREA)
  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • AIDS & HIV (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
CA2856289A 2011-11-18 2012-11-16 Modified rnai agents Pending CA2856289A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161561710P 2011-11-18 2011-11-18
US61/561,710 2011-11-18
PCT/US2012/065601 WO2013074974A2 (en) 2011-11-18 2012-11-16 Modified rnai agents

Publications (1)

Publication Number Publication Date
CA2856289A1 true CA2856289A1 (en) 2013-05-23

Family

ID=47295193

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2856289A Pending CA2856289A1 (en) 2011-11-18 2012-11-16 Modified rnai agents

Country Status (20)

Country Link
US (6) US9796974B2 (https=)
EP (3) EP2780454A2 (https=)
JP (5) JP2015502931A (https=)
KR (5) KR20250133484A (https=)
CN (3) CN105861503A (https=)
AR (1) AR121312A2 (https=)
CA (1) CA2856289A1 (https=)
DK (1) DK3366775T4 (https=)
EA (1) EA201490993A1 (https=)
ES (1) ES2923787T5 (https=)
FI (1) FI3366775T4 (https=)
HK (1) HK1200191A1 (https=)
HR (1) HRP20220908T4 (https=)
IL (2) IL303831A (https=)
IN (1) IN2014CN03465A (https=)
LT (1) LT3366775T (https=)
MX (2) MX385869B (https=)
SG (1) SG11201402382XA (https=)
SI (1) SI3366775T2 (https=)
WO (1) WO2013074974A2 (https=)

Families Citing this family (116)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9657294B2 (en) 2002-02-20 2017-05-23 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
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)
US9228186B2 (en) 2002-11-14 2016-01-05 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US9879266B2 (en) 2002-11-14 2018-01-30 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
EA036772B1 (ru) 2008-10-20 2020-12-18 Элнилэм Фармасьютикалз, Инк. Композиции и способы для ингибирования экспрессии транстиретина
WO2012027206A1 (en) 2010-08-24 2012-03-01 Merck Sharp & Dohme Corp. SINGLE-STRANDED RNAi AGENTS CONTAINING AN INTERNAL, NON-NUCLEIC ACID SPACER
WO2012058210A1 (en) 2010-10-29 2012-05-03 Merck Sharp & Dohme Corp. RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACIDS (siNA)
KR102365961B1 (ko) 2011-03-29 2022-02-23 알닐람 파마슈티칼스 인코포레이티드 Tmprss6 유전자의 발현을 억제하기 위한 조성물 및 방법
ES2923573T3 (es) 2011-06-21 2022-09-28 Alnylam Pharmaceuticals Inc Composiciones de ARNi de proteína 3 de tipo angiopoyetina (ANGPTL3) y métodos de uso de las mismas
HUE048622T2 (hu) * 2011-11-18 2020-08-28 Alnylam Pharmaceuticals Inc RNSi szerek, készítmények és alkalmazási eljárások transztiretin (TTR) asszociált betegségek kezelésére
EP2780454A2 (en) * 2011-11-18 2014-09-24 Alnylam Pharmaceuticals, Inc. Modified rnai agents
US9133461B2 (en) 2012-04-10 2015-09-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the ALAS1 gene
WO2013165816A2 (en) 2012-05-02 2013-11-07 Merck Sharp & Dohme Corp. SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS
US10125369B2 (en) 2012-12-05 2018-11-13 Alnylam Pharmaceuticals, Inc. PCSK9 iRNA compositions and methods of use thereof
CA3216595A1 (en) * 2013-03-14 2014-10-02 Kevin Fitzgerald Complement component c5 irna compositions and methods of use thereof
KR102486617B1 (ko) 2013-05-22 2023-01-12 알닐람 파마슈티칼스 인코포레이티드 Ｔｍｐｒｓｓ6 조성물 및 이의 사용 방법
ES2700277T3 (es) * 2013-05-30 2019-02-14 Univ Nat Corp Tokyo Medical & Dental Agentes de doble cadena para el suministro de oligonucleótidos terapéuticos
TWI768330B (zh) 2013-10-04 2022-06-21 美國西奈山伊坎醫學院 抑制alas1基因表現的組合物及方法
SG10201804960RA (en) * 2013-12-12 2018-07-30 Alnylam Pharmaceuticals Inc Complement component irna compositions and methods of use thereof
WO2015106128A2 (en) * 2014-01-09 2015-07-16 Alnylam Pharmaceuticals, Inc. MODIFIED RNAi AGENTS
AU2015217301A1 (en) * 2014-02-11 2016-08-25 Alnylam Pharmaceuticals, Inc. Ketohexokinase (KHK) 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
AU2015330670B2 (en) 2014-10-10 2022-01-06 Novo Nordisk Health Care Ag Therapeutic inhibition of lactate dehydrogenase and agents therefor
TWI864340B (zh) 2014-10-10 2024-12-01 美商艾爾妮蘭製藥公司 用於抑制hao1(羥酸氧化酶1(乙醇酸鹽氧化酶))基因表現的組合物及方法
TWI710633B (zh) * 2014-11-10 2020-11-21 美商阿尼拉製藥公司 Ｂ型肝炎病毒（ＨＢＶ）ｉＲＮＡ組成物及其用途方法
HK1244843A1 (zh) * 2014-11-17 2018-08-17 Alnylam Pharmaceuticals, Inc. 载脂蛋白c3(apoc3)irna组合物及其使用方法
WO2016085852A1 (en) 2014-11-24 2016-06-02 Alnylam Pharmaceuticals, Inc. Tmprss6 irna compositions and methods of use thereof
WO2016130806A2 (en) 2015-02-13 2016-08-18 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
JP2018509913A (ja) 2015-03-17 2018-04-12 アローヘッド ファーマシューティカルズ インコーポレイテッド 第ｘｉｉ因子の遺伝子発現を阻害するための組成物と方法
CA2979998A1 (en) * 2015-03-20 2016-09-29 Protiva Biotherapeutics, Inc. Compositions and methods for treating hypertriglyceridemia
EA201792263A1 (ru) 2015-04-13 2018-08-31 Элнилэм Фармасьютикалз, Инк. КОМПОЗИЦИИ НА ОСНОВЕ iRNA ПРОТИВ АНГИОПОЭТИН-ПОДОБНОГО БЕЛКА 3 (ANGPTL3) И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
KR102827366B1 (ko) 2015-05-06 2025-07-03 알닐람 파마슈티칼스 인코포레이티드 인자 ＸＩＩ(하게만 인자)(Ｆ12), 칼리크레인 Ｂ, 혈장(플레처 인자) 1(ＫＬＫＢ1) 및 키니노겐 1(ＫＮＧ1) ｉＲＮＡ 조성물 및 그의 이용 방법
EP4365291A3 (en) * 2015-06-12 2024-08-14 Alnylam Pharmaceuticals, Inc. Complement component c5 irna compositions and methods of use thereof
EP3919619A1 (en) * 2015-07-17 2021-12-08 Alnylam Pharmaceuticals, Inc. Multi-targeted single entity conjugates
CN108138182B (zh) 2015-07-31 2022-08-19 阿尔尼拉姆医药品有限公司 甲状腺素运载蛋白(TTR)iRNA组合物及其治疗或预防TTR相关疾病的使用方法
CN118697894A (zh) 2015-08-25 2024-09-27 阿尔尼拉姆医药品有限公司 用于治疗前蛋白转化酶枯草杆菌蛋白酶kexin(pcsk9)基因相关障碍的方法和组合物
US10543286B2 (en) * 2015-10-07 2020-01-28 The Research Foundation For The State University Of New York Methods for increasing platelet count by inhibiting biliverdin IXβ reductase
JP6666002B2 (ja) * 2015-10-07 2020-03-13 国立大学法人京都大学 Ｔｄｐ−４３プロテノパシーの予防又は治療用組成物
EP3436587B1 (en) * 2016-04-01 2021-05-19 Avidity Biosciences, Inc. Phosphatidylinositol-3-kinase nucleic acids and uses thereof
JP2019513371A (ja) 2016-04-01 2019-05-30 アビディティー バイオサイエンシーズ エルエルシー 核酸ポリペプチド組成物とその使用
WO2017173297A1 (en) 2016-04-01 2017-10-05 Avidity Biosciences Llc Beta-catenin nucleic acids and uses thereof
MA45349A (fr) 2016-04-01 2019-02-06 Avidity Biosciences Llc Acides nucléiques egfr et leurs utilisations
MA45340A (fr) * 2016-04-01 2019-02-06 Avidity Biosciences Llc Acides nucléiques du récepteur des androgènes et leurs utilisations
WO2017173304A1 (en) 2016-04-01 2017-10-05 Avidity Biosciences Llc Kras nucleic acids and uses thereof
SG10202008301UA (en) * 2016-04-11 2020-10-29 Arbutus Biopharma Corp Targeted nucleic acid conjugate compositions
MX2019008199A (es) 2017-01-06 2019-11-25 Avidity Biosciences Llc Composiciones de acido nucleico polipeptido y metodos de induccion de la omision de exon.
CA3049133A1 (en) * 2017-01-18 2018-07-26 Alnylam Pharmaceuticals, Inc. Endosomal cleavable linkers
JP7155239B2 (ja) * 2017-04-05 2022-10-18 サイレンス・セラピューティクス・ゲーエムベーハー 産物及び組成物
WO2018191278A2 (en) 2017-04-11 2018-10-18 Arbutus Biopharma Corporation Targeted compositions
US11324820B2 (en) 2017-04-18 2022-05-10 Alnylam Pharmaceuticals, Inc. Methods for the treatment of subjects having a hepatitis b virus (HBV) infection
WO2019006455A1 (en) 2017-06-30 2019-01-03 Solstice Biologics, Ltd. AUXILIARIES OF CHIRAL PHOSPHORAMIDITIS AND METHODS OF USE THEREOF
CA3069451A1 (en) 2017-07-13 2019-01-17 Alnylam Pharmaceuticals, Inc. Methods for inhibition of hao1 (hydroxyacid oxidase 1 (glycolate oxidase)) gene expression
GB201711809D0 (en) 2017-07-21 2017-09-06 Governors Of The Univ Of Alberta Antisense oligonucleotide
MX2020001912A (es) * 2017-09-14 2020-03-24 Arrowhead Pharmaceuticals Inc Agentes de iarn y composiciones para inhibir la expresion de la angiopoyetina tipo 3 (angptl3) y metodos de uso.
KR20250046363A (ko) 2017-09-19 2025-04-02 알닐람 파마슈티칼스 인코포레이티드 트랜스타이레틴(ttr) 매개 아밀로이드증을 치료하기 위한 조성물 및 방법
HRP20231063T1 (hr) 2017-10-13 2023-12-22 Novo Nordisk Health Care Ag Postupci i pripravci namijenjeni inhibiranju eksprimiranja ldha
AU2018350983A1 (en) * 2017-10-18 2020-04-09 Dicerna Pharmaceuticals, Inc. Beta catenin nucleic acid inhibitor molecule
AU2018360697A1 (en) 2017-11-01 2020-05-14 Alnylam Pharmaceuticals, Inc. Complement component C3 iRNA compositions and methods of use thereof
JP7506601B2 (ja) 2017-12-06 2024-06-26 アビディティー バイオサイエンシーズ，インク． 筋萎縮症と筋緊張性ジストロフィーを処置するための組成物および方法
JP7507093B2 (ja) * 2018-03-21 2024-06-27 リジェネロン・ファーマシューティカルズ・インコーポレイテッド １７β－水酸化ステロイド脱水素酵素１３型（ＨＳＤ１７Ｂ１３）ｉＲＮＡ組成物およびその使用方法
WO2019217459A1 (en) 2018-05-07 2019-11-14 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
TWI851574B (zh) * 2018-05-14 2024-08-11 美商阿尼拉製藥公司 血管收縮素原（ＡＧＴ）ｉＲＮＡ組成物及其使用方法
CA3106701A1 (en) 2018-08-13 2020-02-20 Alnylam Pharmaceuticals, Inc. Hepatitis b virus (hbv) dsrna agent compositions and methods of use thereof
CA3105385A1 (en) * 2018-09-18 2020-03-26 Alnylam Pharmaceuticals, Inc. Ketohexokinase (khk) irna compositions and methods of use thereof
CA3118537A1 (en) 2018-11-09 2020-05-14 Alnylam Pharmaceuticals, Inc. Modified double stranded oligonucleotides
EP3894554A1 (en) * 2018-12-10 2021-10-20 Amgen Inc. Chemically-modified rnai constructs and uses thereof
PT3894549T (pt) 2018-12-10 2024-10-16 Amgen Inc Transposase piggybac mutada
IL312067B2 (en) 2018-12-21 2025-08-01 Avidity Biosciences Inc Anti-transferrin receptor antibodies and uses thereof
US12497615B2 (en) 2019-04-25 2025-12-16 Avidity Biosciences, Inc. Nucleic acid compositions and methods of multi-exon skipping
KR20220024153A (ko) 2019-05-24 2022-03-03 엠피리코 인크. 안지오포이에틴 유사 7(angptl7) 관련 질환의 치료
WO2021020412A1 (ja) 2019-07-30 2021-02-04 塩野義製薬株式会社 Ｍｕｒｆ１を標的とする核酸医薬
TW202134435A (zh) 2019-10-22 2021-09-16 美商阿尼拉製藥公司 補體成分ｃ３ ｉｒｎａ組成物及其使用方法
CN115175685B (zh) 2019-12-09 2024-12-13 艾姆皮瑞克公司 用于治疗血管生成素样4(angptl4)相关疾病的寡核苷酸
BR112022011412A2 (pt) 2019-12-16 2022-08-30 Alnylam Pharmaceuticals Inc Composições de irna de domínio de fosfolipase semelhante à patatina contendo proteína 3 (pnpla3) e métodos de uso das mesmas
KR20220143106A (ko) 2020-02-18 2022-10-24 알닐람 파마슈티칼스 인코포레이티드 아포지질단백질 C3 (APOC3) iRNA 조성물 및 이의 사용 방법
WO2021168373A1 (en) * 2020-02-21 2021-08-26 Mitotherapeutix Llc Compositions and methods for inhibiting expression of methylation-controlled j-protein (mcj)
KR20220163960A (ko) 2020-03-06 2022-12-12 알리고스 테라퓨틱스 인코포레이티드 변경된 짧은 개재성 핵산(siNA) 분자 및 이의 용도
US11555190B2 (en) 2020-03-19 2023-01-17 Avidity Biosciences, Inc. Compositions and methods of treating Facioscapulohumeral muscular dystrophy
AU2021241682B2 (en) 2020-03-27 2026-02-12 Avidity Biosciences, Inc. Compositions and methods of treating muscle dystrophy
WO2022072356A1 (en) * 2020-09-29 2022-04-07 Empirico Inc. Compositions and methods for the treatment of angiopoietin like 7 (angptl7) related diseases
CR20230308A (es) 2020-12-11 2023-09-08 Civi Biopharma Inc Entrega oral de conjugados antisentido que tienen por blanco a pcsk9
WO2022174000A2 (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
TW202302847A (zh) 2021-02-26 2023-01-16 美商艾拉倫製藥股份有限公司 己酮糖激酶（ＫＨＫ）ｉＲＮＡ組成物及其使用方法
IL305442A (en) 2021-03-04 2023-10-01 Alnylam Pharmaceuticals Inc Angiopoietin-like 3 (ANGPTL3) IRNA compositions and methods of using them
WO2022212231A2 (en) 2021-03-29 2022-10-06 Alnylam Pharmaceuticals, Inc. Huntingtin (htt) irna agent compositions and methods of use thereof
MX2023012586A (es) 2021-04-26 2023-10-31 Alnylam Pharmaceuticals Inc Composiciones de acido ribonucleico de interferencia (arni) de serina 6, proteasa transmembranaria (tmprss6) y sus metodos de uso.
EP4352231A4 (en) * 2021-06-07 2026-02-11 Empirico Inc TREATMENT OF DISEASES ASSOCIATED WITH ANGPTL4
CA3224904A1 (en) * 2021-06-21 2022-12-29 Shanghai Junshi Biosciences Co., Ltd. Sirna inhibiting angptl3 gene expression and use thereof
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
CA3227852A1 (en) 2021-08-03 2023-02-09 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof
MX2024003266A (es) 2021-09-16 2024-04-03 Avidity Biosciences Inc Composiciones y metodos de tratamiento de la distrofia muscular facioescapulohumeral.
KR20240067943A (ko) 2021-09-24 2024-05-17 알닐람 파마슈티칼스 인코포레이티드 미소관 연관 단백질 타우(MAPT) iRNA 제제 조성물 및 이의 사용 방법
MX2024004011A (es) 2021-10-01 2024-07-01 Adarx Pharmaceuticals Inc Composiciones moduladoras de precalicreína y métodos de uso de estas.
MX2024004437A (es) 2021-10-15 2024-07-01 Alnylam Pharmaceuticals Inc Composiciones de inhibidor de la angiotensina-receptor neprilisina (arni) de administracion extrahepatica y metodos de uso de las mismas.
TW202333749A (zh) 2021-10-29 2023-09-01 美商艾拉倫製藥股份有限公司 補體因子ｂ（ｃｆｂ）ｉｒｎａ組成物及其使用方法
IL312811A (en) 2021-11-16 2024-07-01 Shanghai Argo Biopharmaceutical Co Ltd Composition and method for inhibiting angiotensinogen (agt) protein expression
EP4493570A2 (en) 2022-03-16 2025-01-22 Empirico Inc. Galnac compositions for improving sirna bioavailability
KR20240161967A (ko) 2022-03-16 2024-11-13 다이이찌 산쿄 가부시키가이샤 트랜스페린 수용체 2 의 발현을 억제하는 siRNA
JPWO2023176863A1 (https=) 2022-03-16 2023-09-21
KR20240163743A (ko) 2022-03-28 2024-11-19 엠피리코 인크. 변형된 올리고뉴클레오티드
US12071621B2 (en) 2022-04-05 2024-08-27 Avidity Biosciences, Inc. Anti-transferrin receptor antibody-PMO conjugates for inducing DMD exon 44 skipping
AU2023408479A1 (en) 2022-12-19 2025-05-01 Arnatar Therapeutics, Inc Advanced rna targeting (arnatar)
JP2026507051A (ja) 2023-02-21 2026-02-27 ブイアイビー ブイゼットダブリュ シナプトギリン－３発現を調節するためのオリゴヌクレオチド
WO2024175586A2 (en) 2023-02-21 2024-08-29 Vib Vzw Inhibitors of synaptogyrin-3 expression
WO2024220930A2 (en) 2023-04-20 2024-10-24 Adarx Pharmaceuticals, Inc. Mapt-modulating compositions and methods of use thereof
CN121398851A (zh) 2023-05-12 2026-01-23 阿达尔克斯制药有限公司 Nmda配体缀合的化合物及其用途
IL324720A (en) 2023-05-26 2026-01-01 Adarx Pharmaceuticals Inc SOD1 modulators and methods of using them
EP4562158A1 (en) 2023-06-13 2025-06-04 Arnatar Therapeutics, Inc Advanced rna targeting (arnatar) for angiotensinogen
CN121712891A (zh) 2023-06-20 2026-03-20 阿达尔克斯制药有限公司 Lrrk2调节组合物及其使用方法
CN121816417A (zh) * 2023-07-21 2026-04-07 倍臻生物技术（苏州）有限公司 双链寡核苷酸药剂和其用途
WO2025064660A2 (en) 2023-09-21 2025-03-27 Alnylam Pharmaceuticals, Inc. Activin a receptor type 1c (acvr1c) irna compositions and methods of use thereof
EP4671372A3 (en) 2024-01-29 2026-03-11 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
TW202602463A (zh) 2024-03-22 2026-01-16 日商武田藥品工業股份有限公司 用於抑制細胞色素ｐ４５０家族７次家族ａ成員１（ｃｙｐ７ａ１）表現之組成物及方法
WO2026041784A1 (en) 2024-08-23 2026-02-26 Vib Vzw Oligonucleotides for modulating synaptogyrin-3 expression
CN121718637A (zh) * 2026-02-14 2026-03-24 重庆医科大学附属第一医院 一种基于MNAzyme-AS1411双信号放大系统的探针及其应用

Family Cites Families (81)

* 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
US5122808A (en) 1990-09-28 1992-06-16 Allied-Signal Inc. Phase only bearing mesurement with amiguity correction in a collision avoidance system
US5283185A (en) 1991-08-28 1994-02-01 University Of Tennessee Research Corporation Method for delivering nucleic acids into cells
EP0646178A1 (en) 1992-06-04 1995-04-05 The Regents Of The University Of California expression cassette with regularoty regions functional in the mammmlian host
JPH07508410A (ja) 1992-06-18 1995-09-21 ジェンファーム　インターナショナル　インコーポレイテッド 酵母人工染色体を有するトランスジェニック非ヒト動物の製造方法
JPH11508231A (ja) 1995-05-26 1999-07-21 ソマティックス セラピー コーポレイション 安定な脂質／核酸複合体を含む送達ビヒクル
US6034135A (en) 1997-03-06 2000-03-07 Promega Biosciences, Inc. Dimeric cationic lipids
WO2003070918A2 (en) * 2002-02-20 2003-08-28 Ribozyme Pharmaceuticals, Incorporated Rna interference by modified short interfering nucleic acid
WO2005019453A2 (en) 2001-05-18 2005-03-03 Sirna Therapeutics, Inc. 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)
US20050148530A1 (en) * 2002-02-20 2005-07-07 Sirna Therapeutics, Inc. RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA)
US20060217331A1 (en) * 2001-05-18 2006-09-28 Sirna Therapeutics, Inc. Chemically modified double stranded nucleic acid molecules that mediate RNA interference
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)
AU2003207708A1 (en) * 2002-02-20 2003-09-09 Sirna Therapeutics, Inc. Rna interference mediated inhibition of map kinase genes
AU2003260370B2 (en) * 2002-08-05 2008-05-22 Silence Therapeutics Gmbh Further novel forms of interfering RNA molecules
CA2500224C (en) * 2002-09-25 2015-04-28 University Of Massachusetts In vivo gene silencing by chemically modified and stable sirna
US8604183B2 (en) * 2002-11-05 2013-12-10 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2′-modified nucleosides for use in gene modulation
US20040198640A1 (en) * 2003-04-02 2004-10-07 Dharmacon, Inc. Stabilized polynucleotides for use in RNA interference
ATE439438T1 (de) * 2003-05-23 2009-08-15 Sirna Therapeutics Inc Durch rna-interferenz vermittelte hemmung der genexpression unter verwendung von chemisch modifizierter sina (short interfering nucleic acid)
US7683036B2 (en) 2003-07-31 2010-03-23 Regulus Therapeutics Inc. Oligomeric compounds and compositions for use in modulation of small non-coding RNAs
WO2005035759A2 (en) 2003-08-20 2005-04-21 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF HYPOXIA INDUCIBLE FACTOR 1 (HIF1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20070265220A1 (en) 2004-03-15 2007-11-15 City Of Hope Methods and compositions for the specific inhibition of gene expression by double-stranded RNA
EP2399924B1 (en) 2004-05-27 2015-01-28 Alnylam Pharmaceuticals, Inc. Nuclease resistant double-stranded ribonucleic acid
AU2005252663B2 (en) * 2004-06-03 2011-07-07 Isis Pharmaceuticals, Inc. Double strand compositions comprising differentially modified strands for use in gene modulation
US7528118B2 (en) * 2004-09-24 2009-05-05 Alnylam Pharmaceuticals, Inc. RNAi modulation of ApoB and uses thereof
US20070213292A1 (en) * 2005-08-10 2007-09-13 The Rockefeller University Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof
WO2007031877A2 (en) * 2005-09-16 2007-03-22 Coley Pharmaceutical Gmbh Modulation of immunostimulatory properties of short interfering ribonucleic acid (sirna) by nucleotide modification
US20070099858A1 (en) * 2005-10-03 2007-05-03 Sirna Therapeutics, Inc. RNA interference mediated of inhibition of influenza virus gene expression using short interfering nucleic acid (siNA)
JP2009509566A (ja) * 2005-10-03 2009-03-12 サーナ・セラピューティクス・インコーポレイテッド 低分子干渉核酸を用いた、ｒｎａ干渉によって媒介される、インフルエンザウイルス遺伝子発現の阻害
US8101741B2 (en) * 2005-11-02 2012-01-24 Protiva Biotherapeutics, Inc. Modified siRNA molecules and uses thereof
EP1989307B1 (en) 2006-02-08 2012-08-08 Quark Pharmaceuticals, Inc. NOVEL TANDEM siRNAS
CN101410518A (zh) * 2006-03-24 2009-04-15 诺瓦提斯公司 治疗HPV感染的dsRNA组合物和方法
EP2021008B1 (en) 2006-04-07 2015-12-02 Idera Pharmaceuticals, Inc. Stabilized immune modulatory rna (simra) compounds for tlr7 and tlr8
AU2007275365A1 (en) * 2006-07-17 2008-01-24 Sirna Therapeutics Inc. RNA interference mediated inhibition of Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA)
US20110046206A1 (en) * 2007-06-22 2011-02-24 Isis Pharmaceuticals, Inc. Double strand compositions comprising differentially modified strands for use in gene modulation
CA2692161C (en) 2007-07-09 2015-09-29 Idera Pharmaceuticals, Inc. Stabilized immune modulatory rna (simra) compounds
WO2009082607A2 (en) * 2007-12-04 2009-07-02 Alnylam Pharmaceuticals, Inc. Targeting lipids
MX2010008394A (es) 2008-01-31 2010-11-12 Alnylam Pharmaceuticals Inc Metodos optimizados para administracion de arndc focalizando el gen pcsk9.
CN102037123A (zh) * 2008-04-04 2011-04-27 卡兰多制药股份有限公司 Epas1抑制剂的组合物和用途
TWI455944B (zh) * 2008-07-01 2014-10-11 Daiichi Sankyo Co Ltd 雙股多核苷酸
CA2746527A1 (en) * 2008-09-22 2010-03-25 Rxi Pharmaceuticals Corporation Rna interference in skin indications
SG171737A1 (en) * 2008-11-17 2011-07-28 Hoffmann La Roche Compositions and methods for inhibiting expression of factor vii genes
US9493774B2 (en) * 2009-01-05 2016-11-15 Rxi Pharmaceuticals Corporation Inhibition of PCSK9 through RNAi
EP2408458A1 (en) 2009-03-19 2012-01-25 Merck Sharp&Dohme Corp. RNA INTERFERENCE MEDIATED INHIBITION OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 6 (STAT6) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
EP2408915A2 (en) 2009-03-19 2012-01-25 Merck Sharp&Dohme Corp. RNA INTERFERENCE MEDIATED INHIBITION OF GATA BINDING PROTEIN 3 (GATA3) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
ES2804764T3 (es) 2009-06-01 2021-02-09 Halo Bio Rnai Therapeutics Inc Polinucleótidos para la interferencia de ARN multivalente, composiciones y métodos de uso de los mismos
NZ597504A (en) * 2009-06-15 2013-10-25 Alnylam Pharmaceuticals Inc Lipid formulated dsrna targeting the pcsk9 gene
DK2470656T3 (da) 2009-08-27 2015-06-22 Idera Pharmaceuticals Inc Sammensætning til hæmning af genekspression og anvendelser heraf
KR101718534B1 (ko) * 2009-12-09 2017-03-22 닛토덴코 가부시키가이샤 Ｈｓｐ４７ 발현의 조절
US8653047B2 (en) * 2010-01-08 2014-02-18 Isis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
EP3329924B1 (en) * 2010-03-29 2021-05-05 Alnylam Pharmaceuticals, Inc. Dsrna therapy for transthyretin (ttr) related ocular amyloidosis
CA2812046A1 (en) * 2010-09-15 2012-03-22 Alnylam Pharmaceuticals, Inc. Modified irna agents
CN102051362B (zh) * 2010-11-02 2013-10-16 中国人民解放军军事医学科学院生物工程研究所 靶向hpip基因的干扰性rna、含有该干扰性rna的药物组合物及其应用
KR101390966B1 (ko) 2010-12-30 2014-06-30 주식회사 삼양바이오팜 Ｈｉｆｌａ의 발현을 저해하는 ｓｉＲＮＡ 및 이를 포함하는 항암 조성물
JP2014506791A (ja) * 2011-02-03 2014-03-20 マーナ セラピューティクス インコーポレイテッド ｍｉＲ−３４の合成模倣体
EP2780454A2 (en) * 2011-11-18 2014-09-24 Alnylam Pharmaceuticals, Inc. Modified rnai agents
HUE048622T2 (hu) * 2011-11-18 2020-08-28 Alnylam Pharmaceuticals Inc RNSi szerek, készítmények és alkalmazási eljárások transztiretin (TTR) asszociált betegségek kezelésére
US9127274B2 (en) * 2012-04-26 2015-09-08 Alnylam Pharmaceuticals, Inc. Serpinc1 iRNA compositions and methods of use thereof
WO2014022739A2 (en) * 2012-08-03 2014-02-06 Alnylam Pharmaceuticals, Inc. Modified rnai agents
US10125369B2 (en) * 2012-12-05 2018-11-13 Alnylam Pharmaceuticals, Inc. PCSK9 iRNA compositions and methods of use thereof
CA3216595A1 (en) * 2013-03-14 2014-10-02 Kevin Fitzgerald Complement component c5 irna compositions and methods of use thereof
TW201936624A (zh) * 2013-05-22 2019-09-16 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
KR102486617B1 (ko) * 2013-05-22 2023-01-12 알닐람 파마슈티칼스 인코포레이티드 Ｔｍｐｒｓｓ6 조성물 및 이의 사용 방법
WO2015106128A2 (en) * 2014-01-09 2015-07-16 Alnylam Pharmaceuticals, Inc. MODIFIED RNAi AGENTS
IL316808A (en) * 2014-08-20 2025-01-01 Alnylam Pharmaceuticals Inc Modified double-stranded RNA materials and their uses
HK1244843A1 (zh) * 2014-11-17 2018-08-17 Alnylam Pharmaceuticals, Inc. 载脂蛋白c3(apoc3)irna组合物及其使用方法
WO2016130806A2 (en) * 2015-02-13 2016-08-18 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
US10833934B2 (en) 2015-06-30 2020-11-10 British Telecommunications Public Limited Company Energy management in a network
CN108138182B (zh) * 2015-07-31 2022-08-19 阿尔尼拉姆医药品有限公司 甲状腺素运载蛋白(TTR)iRNA组合物及其治疗或预防TTR相关疾病的使用方法
WO2017100542A1 (en) * 2015-12-10 2017-06-15 Alnylam Pharmaceuticals, Inc. Sterol regulatory element binding protein (srebp) chaperone (scap) irna compositions and methods of use thereof
CN111845757A (zh) 2019-04-30 2020-10-30 通用汽车环球科技运作有限责任公司 分心驾驶消除系统
CN110649043B (zh) 2019-09-30 2021-11-19 厦门天马微电子有限公司 阵列基板、显示面板、显示装置及阵列基板的制备方法
KR102318555B1 (ko) 2020-03-19 2021-10-29 한국과학기술연구원 광소자용 역나노콘과 그 제조방법

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