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)
  • Saccharide Compounds (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (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
MX2020011570A (es) 2018-05-07 2020-11-24 Alnylam Pharmaceuticals Inc Administracion extrahepatica.
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
EP4314296A2 (en) 2021-03-29 2024-02-07 Alnylam Pharmaceuticals, Inc. Huntingtin (htt) irna agent compositions and methods of use thereof
TW202328449A (zh) 2021-09-24 2023-07-16 美商艾拉倫製藥公司 微管相關蛋白ＴＡＵ（ＭＡＰＴ）ｉＲＮＡ試劑組合物及其使用方法
US11879125B2 (en) 2022-03-16 2024-01-23 Empirico Inc. GalNAc compositions for improving siRNA bioavailability
AU2023245603A1 (en) 2022-03-28 2024-11-07 Empirico Inc. Modified oligonucleotides
AU2023313030A1 (en) * 2022-07-27 2025-01-09 E-Therapeutics Plc Nucleic acid compounds
WO2024073732A1 (en) * 2022-09-30 2024-04-04 Alnylam Pharmaceuticals, Inc. Modified double-stranded rna agents
EP4700125A2 (en) * 2023-04-21 2026-02-25 Suzhou Siran Biotechnology Co., Ltd. Oligomeric nucleic acid, and preparation method therefore and use thereof
WO2025064821A2 (en) 2023-09-21 2025-03-27 Ionis Pharmaceuticals, Inc. Compounds and methods for inhibiting 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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US7812149B2 (en) * 1996-06-06 2010-10-12 Isis Pharmaceuticals, Inc. 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations
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
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
US10913767B2 (en) 2010-04-22 2021-02-09 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising acyclic and abasic nucleosides and analogs
EP2563922A1 (en) 2010-04-26 2013-03-06 Marina Biotech, Inc. Nucleic acid compounds with conformationally restricted monomers and uses thereof
US10119136B2 (en) 2014-01-09 2018-11-06 Alnylam Pharmaceuticals, Inc. RNAi agents modified at the 4′-C position
DK3569711T3 (da) 2014-12-15 2021-02-22 Dicerna Pharmaceuticals Inc Ligandmodificerede dobbeltstrengede nukleinsyrer
WO2016209862A1 (en) 2015-06-23 2016-12-29 Alnylam Pharmaceuticals, Inc. Glucokinase (gck) irna compositions and methods of use thereof
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Also Published As

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

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