CA3086485A1 - Chirally-enriched double-stranded rna agents - Google Patents

Chirally-enriched double-stranded rna agents Download PDF

Info

Publication number
CA3086485A1
CA3086485A1 CA3086485A CA3086485A CA3086485A1 CA 3086485 A1 CA3086485 A1 CA 3086485A1 CA 3086485 A CA3086485 A CA 3086485A CA 3086485 A CA3086485 A CA 3086485A CA 3086485 A1 CA3086485 A1 CA 3086485A1
Authority
CA
Canada
Prior art keywords
chirally
modified
linkage
dsrna agent
antisense strand
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
CA3086485A
Other languages
English (en)
French (fr)
Inventor
Muthiah Manoharan
Nate TANEJA
Hartmut Ingo JAHNS
Shigeo Matsuda
Klaus CHARISSE
Guo He
Jayaprakash K. Nair
Christopher Brown
Mark K. SCHLEGEL
Vasant Jadhav
Martin Maier
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
Application filed by Alnylam Pharmaceuticals Inc filed Critical Alnylam Pharmaceuticals Inc
Publication of CA3086485A1 publication Critical patent/CA3086485A1/en
Pending legal-status Critical Current

Links

Classifications

    • 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
    • C12N15/11—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
    • C12N15/1136—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 against growth factors, growth regulators, cytokines, lymphokines or hormones
    • 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 nucleic acids [NA]
    • 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
    • C12N2310/34—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
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Endocrinology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)
  • Medicinal Preparation (AREA)
CA3086485A 2017-12-21 2018-12-21 Chirally-enriched double-stranded rna agents Pending CA3086485A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201762609093P 2017-12-21 2017-12-21
US62/609,093 2017-12-21
PCT/US2018/067103 WO2019126651A1 (en) 2017-12-21 2018-12-21 Chirally-enriched double-stranded rna agents

Publications (1)

Publication Number Publication Date
CA3086485A1 true CA3086485A1 (en) 2019-06-27

Family

ID=65041929

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3086485A Pending CA3086485A1 (en) 2017-12-21 2018-12-21 Chirally-enriched double-stranded rna agents

Country Status (6)

Country Link
US (2) US11597932B2 (enExample)
EP (1) EP3728281A1 (enExample)
JP (2) JP7348185B2 (enExample)
AU (2) AU2018392782B2 (enExample)
CA (1) CA3086485A1 (enExample)
WO (1) WO2019126651A1 (enExample)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112007045A (zh) 2012-07-13 2020-12-01 波涛生命科学有限公司 手性控制
AU2019266207B2 (en) 2018-05-07 2025-04-24 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
JP2023526533A (ja) * 2020-05-22 2023-06-21 ウェイブ ライフ サイエンシズ リミテッド 二本鎖オリゴヌクレオチド組成物及びそれに関連する方法
US20230257745A1 (en) 2020-07-10 2023-08-17 Alnylam Pharmaceuticals, Inc. Circular siRNAs
US20250270562A1 (en) 2021-07-09 2025-08-28 Alnylam Pharmaceuticals, Inc. Bis-rnai compounds for cns delivery
CN118139977A (zh) * 2021-09-21 2024-06-04 波涛生命科学有限公司 双链寡核苷酸组合物及其相关方法
EP4433596A2 (en) * 2021-11-19 2024-09-25 Wave Life Sciences Ltd. Hsd17b13-related double stranded oligonucleotide compositions and methods relating thereto
CN114230624A (zh) * 2021-12-22 2022-03-25 上海兆维科技发展有限公司 一种核苷二聚体亚膦酰胺的合成方法
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
KR20240163743A (ko) 2022-03-28 2024-11-19 엠피리코 인크. 변형된 올리고뉴클레오티드
EP4522742A2 (en) 2022-05-13 2025-03-19 Alnylam Pharmaceuticals, Inc. Single-stranded loop oligonucleotides
WO2023235817A1 (en) * 2022-06-02 2023-12-07 Ionis Pharmaceuticals, Inc. Linkage modified oligomeric compounds and uses thereof
WO2024238385A2 (en) 2023-05-12 2024-11-21 Alnylam Pharmaceuticals, Inc. Single-stranded loop oligonucleotides

Family Cites Families (37)

* 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
US4469863A (en) 1980-11-12 1984-09-04 Ts O Paul O P Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
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
US5256775A (en) 1989-06-05 1993-10-26 Gilead Sciences, Inc. Exonuclease-resistant oligonucleotides
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5130302A (en) 1989-12-20 1992-07-14 Boron Bilogicals, Inc. Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5457191A (en) 1990-01-11 1995-10-10 Isis Pharmaceuticals, Inc. 3-deazapurines
US5149797A (en) 1990-02-15 1992-09-22 The Worcester Foundation For Experimental Biology Method of site-specific alteration of rna and production of encoded polypeptides
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
JPH0874B2 (ja) 1990-07-27 1996-01-10 アイシス・ファーマシューティカルス・インコーポレーテッド 遺伝子発現を検出および変調するヌクレアーゼ耐性、ピリミジン修飾オリゴヌクレオチド
US5283185A (en) 1991-08-28 1994-02-01 University Of Tennessee Research Corporation Method for delivering nucleic acids into cells
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
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
WO1994000569A1 (en) 1992-06-18 1994-01-06 Genpharm International, Inc. Methods for producing transgenic non-human animals harboring a yeast artificial chromosome
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
GB9304620D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Compounds
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
DE19956568A1 (de) 1999-01-30 2000-08-17 Roland Kreutzer Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens
KR100909681B1 (ko) 2000-12-01 2009-07-29 막스-플랑크-게젤샤프트 츄어 푀르더룽 데어 비쎈샤프텐 에.파우. Ｒｎａ 간섭을 매개하는 작은 ｒｎａ 분자
US7723509B2 (en) * 2003-04-17 2010-05-25 Alnylam Pharmaceuticals IRNA agents with biocleavable tethers
CA2542232A1 (en) 2003-06-09 2005-01-20 Alnylam Pharmaceuticals, Inc. Method for treating neurodegenerative disease by inhibiting alpha-synuclein
WO2009082607A2 (en) 2007-12-04 2009-07-02 Alnylam Pharmaceuticals, Inc. Targeting lipids
WO2012018881A2 (en) * 2010-08-03 2012-02-09 Alnylam Pharmaceuticals, Inc. Methods and compositions for the regulation of rna
EP2616543A1 (en) 2010-09-15 2013-07-24 Alnylam Pharmaceuticals, Inc. MODIFIED iRNA AGENTS
CN112007045A (zh) * 2012-07-13 2020-12-01 波涛生命科学有限公司 手性控制
CN113278617A (zh) 2014-01-16 2021-08-20 波涛生命科学有限公司 手性设计
IL316808A (en) * 2014-08-20 2025-01-01 Alnylam Pharmaceuticals Inc Modified double-stranded RNA materials and their uses
JOP20200092A1 (ar) * 2014-11-10 2017-06-16 Alnylam Pharmaceuticals Inc تركيبات iRNA لفيروس الكبد B (HBV) وطرق لاستخدامها
NZ781029A (en) * 2015-10-09 2025-07-25 Wave Life Sciences Ltd Oligonucleotide compositions and methods thereof
WO2017214518A1 (en) * 2016-06-10 2017-12-14 Alnylam Pharmaceuticals, Inc. COMPLETMENT COMPONENT C5 iRNA COMPOSTIONS AND METHODS OF USE THEREOF FOR TREATING PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)
WO2018035380A1 (en) 2016-08-17 2018-02-22 Solstice Biologics, Ltd. Polynucleotide constructs
KR102318555B1 (ko) 2020-03-19 2021-10-29 한국과학기술연구원 광소자용 역나노콘과 그 제조방법

Also Published As

Publication number Publication date
AU2018392782B2 (en) 2023-08-31
US11597932B2 (en) 2023-03-07
AU2023274165A1 (en) 2023-12-21
JP7348185B2 (ja) 2023-09-20
AU2023274165B2 (en) 2025-09-18
JP2021507709A (ja) 2021-02-25
AU2018392782A1 (en) 2021-12-16
JP2023171757A (ja) 2023-12-05
US20230122244A1 (en) 2023-04-20
WO2019126651A1 (en) 2019-06-27
US20210207144A1 (en) 2021-07-08
EP3728281A1 (en) 2020-10-28

Similar Documents

Publication Publication Date Title
JP7654744B2 (ja) 修飾二本鎖ｒｎａ剤
US20230122244A1 (en) Chirally-enriched double-stranded rna agents
WO2015106128A2 (en) MODIFIED RNAi AGENTS
EP2880162A2 (en) Modified rnai agents
EP3790557A2 (en) Compositions and methods for improving strand biased
HK40121704A (en) Modified double-stranded rna agents
HK40051291A (en) Modified double-stranded rna agents
HK40051656A (en) Modified double-stranded rna agents
EA043057B1 (ru) Средства, представляющие собой модифицированную двухнитевую рнк

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20231218