AU2019270152B2 - Modified RNA agents with reduced off-target effect - Google Patents

Modified RNA agents with reduced off-target effect Download PDF

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Publication number
AU2019270152B2
AU2019270152B2 AU2019270152A AU2019270152A AU2019270152B2 AU 2019270152 B2 AU2019270152 B2 AU 2019270152B2 AU 2019270152 A AU2019270152 A AU 2019270152A AU 2019270152 A AU2019270152 A AU 2019270152A AU 2019270152 B2 AU2019270152 B2 AU 2019270152B2
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Australia
Prior art keywords
muna
gna
dsrna
antisense strand
ome
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AU2019270152A
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AU2019270152A1 (en
Inventor
Klaus CHARISSE
Vasant R. Jadhav
Maja JANAS
Martin Maier
Muthiah Manoharan
Shigeo Matsuda
Jayaprakash K. Nair
Kallanthottathil G. Rajeev
Mark K. SCHLEGEL
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Alnylam Pharmaceuticals Inc
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Alnylam Pharmaceuticals Inc
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Publication of AU2019270152A1 publication Critical patent/AU2019270152A1/en
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Priority to AU2025206406A priority Critical patent/AU2025206406A1/en
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    • 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
    • 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
    • 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
    • C12N2310/318—Chemical structure of the backbone where the PO2 is completely replaced, e.g. MMI or formacetal
    • 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
    • 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
    • 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
    • C12N2310/50—Physical structure
    • C12N2310/53—Physical structure partially self-complementary or closed
    • 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
    • C12N2320/53—Methods for regulating/modulating their activity reducing unwanted side-effects

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  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Wood Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Saccharide Compounds (AREA)
AU2019270152A 2018-05-16 2019-05-16 Modified RNA agents with reduced off-target effect Active AU2019270152B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2025206406A AU2025206406A1 (en) 2018-05-16 2025-07-22 Modified rna agents with reduced off-target effect

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201862672405P 2018-05-16 2018-05-16
US62/672,405 2018-05-16
US201862719291P 2018-08-17 2018-08-17
US62/719,291 2018-08-17
PCT/US2019/032633 WO2019222479A1 (en) 2018-05-16 2019-05-16 Modified rna agents with reduced off-target effect

Related Child Applications (1)

Application Number Title Priority Date Filing Date
AU2025206406A Division AU2025206406A1 (en) 2018-05-16 2025-07-22 Modified rna agents with reduced off-target effect

Publications (2)

Publication Number Publication Date
AU2019270152A1 AU2019270152A1 (en) 2020-12-10
AU2019270152B2 true AU2019270152B2 (en) 2025-05-08

Family

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Family Applications (2)

Application Number Title Priority Date Filing Date
AU2019270152A Active AU2019270152B2 (en) 2018-05-16 2019-05-16 Modified RNA agents with reduced off-target effect
AU2025206406A Pending AU2025206406A1 (en) 2018-05-16 2025-07-22 Modified rna agents with reduced off-target effect

Family Applications After (1)

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AU2025206406A Pending AU2025206406A1 (en) 2018-05-16 2025-07-22 Modified rna agents with reduced off-target effect

Country Status (6)

Country Link
US (3) US12247203B2 (enExample)
EP (1) EP3802827A4 (enExample)
JP (3) JP7384833B2 (enExample)
AU (2) AU2019270152B2 (enExample)
CA (1) CA3099930A1 (enExample)
WO (1) WO2019222479A1 (enExample)

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US11597744B2 (en) 2017-06-30 2023-03-07 Sirius Therapeutics, Inc. Chiral phosphoramidite auxiliaries and methods of their use
CA3098623A1 (en) 2018-05-07 2019-11-14 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
EP4114947A1 (en) 2020-03-05 2023-01-11 Alnylam Pharmaceuticals, Inc. Complement component c3 irna compositions and methods of use thereof for treating or preventing complement component c3-associated diseases
KR20230043195A (ko) * 2020-08-04 2023-03-30 투오지에 바이오텍 (상하이) 컴퍼니 리미티드 오프-타겟 활성이 감소된 변형된 siRNA
EP4291654A2 (en) 2021-02-12 2023-12-20 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
CN113073098B (zh) * 2021-02-20 2024-08-20 北京理工大学 抑制BACE1基因表达的siRNA修饰物及其应用
BR112023019981A2 (pt) 2021-03-29 2023-12-12 Alnylam Pharmaceuticals Inc Composições do agente irna de huntingtina (htt) e métodos de uso das mesmas
WO2022206946A1 (zh) * 2021-04-02 2022-10-06 上海拓界生物医药科技有限公司 乙型肝炎病毒siRNA和siRNA缀合物
KR20240067943A (ko) 2021-09-24 2024-05-17 알닐람 파마슈티칼스 인코포레이티드 미소관 연관 단백질 타우(MAPT) iRNA 제제 조성물 및 이의 사용 방법
IL315546A (en) 2022-03-16 2024-11-01 Empirico Inc GALNAC compositions to improve siRNA bioavailability
EP4499834A2 (en) 2022-03-28 2025-02-05 Empirico Inc. Modified oligonucleotides
WO2024023256A1 (en) * 2022-07-27 2024-02-01 E-Therapeutics Plc Nucleic acid compounds
JP2025532985A (ja) * 2022-09-30 2025-10-03 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 修飾二本鎖ｒｎａ剤
AU2024258620A1 (en) * 2023-04-21 2025-11-06 Suzhou Siran Biotechnology Co., Ltd. Oligomeric nucleic acid, and preparation method therefore and use thereof
UY40897A (es) 2023-09-21 2025-03-31 Ionis Pharmaceuticals Inc Compuestos y métodos para inhibir lpa
US12454693B1 (en) * 2024-09-27 2025-10-28 Dexcel Pharma Technologies Ltd. Nucleic acids for inhibiting expression of transferrin receptor 2

Citations (1)

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WO2016028649A1 (en) * 2014-08-20 2016-02-25 Alnylam Pharmaceuticals, Inc. Modified double-stranded rna agents

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US20050032069A1 (en) 2002-11-05 2005-02-10 Muthiah Manoharan Oligomeric compounds having modified bases for binding to adenine and guanine and their use in gene modulation
US7812149B2 (en) * 1996-06-06 2010-10-12 Isis Pharmaceuticals, Inc. 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations
EP2152877A2 (en) * 2007-05-02 2010-02-17 Sirna Therapeutics Inc. RNA INTERFERENCE MEDIATED INHIBITION OF CYCLIC NUCLEOTIDE TYPE 4 PHOSPHODIESTERASE ( PDE4B) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
CN102753187A (zh) * 2009-06-03 2012-10-24 戴瑟纳制药公司 肽-dicer底物试剂及其特异性抑制基因表达的方法
WO2011133876A2 (en) 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising acyclic and abasic nucleosides and analogs
US20130190383A1 (en) * 2010-04-26 2013-07-25 Marina Biotech, Inc. Nucleic acid compounds with conformationally restricted monomers and uses thereof
WO2015106128A2 (en) * 2014-01-09 2015-07-16 Alnylam Pharmaceuticals, Inc. MODIFIED RNAi AGENTS
EP3865576A1 (en) 2014-12-15 2021-08-18 Dicerna Pharmaceuticals, Inc. Ligand-modified double-stranded nucleic acids
WO2016209862A1 (en) 2015-06-23 2016-12-29 Alnylam Pharmaceuticals, Inc. Glucokinase (gck) irna compositions and methods of use thereof
JP6924744B2 (ja) * 2015-07-17 2021-08-25 アークトゥラス・セラピューティクス・インコーポレイテッドＡｒｃｔｕｒｕｓ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． Ｂ型肝炎ウイルスに対する組成物および薬剤ならびにその使用
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Also Published As

Publication number Publication date
EP3802827A1 (en) 2021-04-14
US20250207131A1 (en) 2025-06-26
CA3099930A1 (en) 2019-11-21
JP2024014905A (ja) 2024-02-01
US12247203B2 (en) 2025-03-11
US20210238595A1 (en) 2021-08-05
JP2025113272A (ja) 2025-08-01
AU2025206406A1 (en) 2025-08-14
JP7684373B2 (ja) 2025-05-27
WO2019222479A1 (en) 2019-11-21
US12275938B2 (en) 2025-04-15
JP2021523720A (ja) 2021-09-09
JP7384833B2 (ja) 2023-11-21
AU2019270152A1 (en) 2020-12-10
EP3802827A4 (en) 2022-08-03
US20220290145A1 (en) 2022-09-15

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