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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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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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Molecular Biology (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)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (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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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 (https=)
EP (1) EP3802827A4 (https=)
JP (3) JP7384833B2 (https=)
AU (2) AU2019270152B2 (https=)
CA (1) CA3099930A1 (https=)
WO (1) WO2019222479A1 (https=)

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WO2019006455A1 (en) 2017-06-30 2019-01-03 Solstice Biologics, Ltd. AUXILIARIES OF CHIRAL PHOSPHORAMIDITIS AND METHODS OF USE THEREOF
WO2019217459A1 (en) 2018-05-07 2019-11-14 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
WO2021178607A1 (en) * 2020-03-05 2021-09-10 Alnylam Pharmaceuticals, Inc. Complement component c3 irna compositions and methods of use thereof for treating or preventing complement component c3-associated diseases
TW202214858A (zh) * 2020-08-04 2022-04-16 大陸商上海拓界生物醫藥科技有限公司 脫靶活性降低的修飾siRNA
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
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
WO2022212231A2 (en) 2021-03-29 2022-10-06 Alnylam Pharmaceuticals, Inc. Huntingtin (htt) irna agent compositions and methods of use thereof
KR20240067943A (ko) 2021-09-24 2024-05-17 알닐람 파마슈티칼스 인코포레이티드 미소관 연관 단백질 타우(MAPT) iRNA 제제 조성물 및 이의 사용 방법
EP4493570A2 (en) 2022-03-16 2025-01-22 Empirico Inc. Galnac compositions for improving sirna bioavailability
KR20240163743A (ko) 2022-03-28 2024-11-19 엠피리코 인크. 변형된 올리고뉴클레오티드
JP2025524135A (ja) * 2022-07-27 2025-07-25 イー－セラピューティクス・ピーエルシー 核酸化合物
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
WO2024217152A2 (zh) * 2023-04-21 2024-10-24 苏州时安生物技术有限公司 一种寡聚核酸及其制备方法和应用
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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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)
JP2012528596A (ja) 2009-06-03 2012-11-15 ダイセルナ ファーマシューティカルズ， インコーポレイテッド ペプチドダイサー基質剤およびその特異的な遺伝子発現阻害のための方法
US10913767B2 (en) 2010-04-22 2021-02-09 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
JP7105065B2 (ja) * 2014-12-15 2022-07-22 ダイセルナ ファーマシューティカルズ， インコーポレイテッド リガンド修飾二本鎖核酸
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
KR102645243B1 (ko) * 2016-11-23 2024-03-11 알닐람 파마슈티칼스 인코포레이티드 표적외 효과가 감소된 변형 rna 작용제

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Also Published As

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

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