CN116472063A - 包含经修饰的siRNA的靶向性偶联物 - Google Patents

包含经修饰的siRNA的靶向性偶联物 Download PDF

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Publication number
CN116472063A
CN116472063A CN202180078408.9A CN202180078408A CN116472063A CN 116472063 A CN116472063 A CN 116472063A CN 202180078408 A CN202180078408 A CN 202180078408A CN 116472063 A CN116472063 A CN 116472063A
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salt
compound
group
conjugate
chloro
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CN202180078408.9A
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Chinese (zh)
Inventor
欧文·M·戴利
艾米·C·H·李
迈克尔·J·索菲娅
埃米莉·P·悌
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Protiva Biotherapeutics Inc
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Protiva Biotherapeutics Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
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    • A61P31/20—Antivirals for DNA viruses
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    • 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
    • C12N15/1131—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 viruses
    • 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
    • A61K48/0008—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
    • A61K48/0025—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid
    • A61K48/0033—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid the non-active part being non-polymeric
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    • 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
    • C12N2310/322—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
    • C12N2310/32—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
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol
    • 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

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Organic Chemistry (AREA)
  • Virology (AREA)
  • Biochemistry (AREA)
  • Epidemiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Communicable Diseases (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicinal Preparation (AREA)
CN202180078408.9A 2020-11-06 2021-11-05 包含经修饰的siRNA的靶向性偶联物 Pending CN116472063A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US202063110837P 2020-11-06 2020-11-06
US63/110,837 2020-11-06
PCT/US2021/058232 WO2022098990A1 (en) 2020-11-06 2021-11-05 Targeted conjugates comprising modified sirna

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Publication Number Publication Date
CN116472063A true CN116472063A (zh) 2023-07-21

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CN202180078408.9A Pending CN116472063A (zh) 2020-11-06 2021-11-05 包含经修饰的siRNA的靶向性偶联物

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US (1) US20240052349A1 (https=)
EP (1) EP4240369A4 (https=)
JP (1) JP2023548295A (https=)
KR (1) KR20230104652A (https=)
CN (1) CN116472063A (https=)
AU (1) AU2021376390A1 (https=)
CA (1) CA3199757A1 (https=)
IL (1) IL302530A (https=)
MX (1) MX2023005138A (https=)
TW (1) TW202233243A (https=)
WO (1) WO2022098990A1 (https=)

Cited By (1)

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WO2026061476A1 (zh) * 2024-09-19 2026-03-26 长春金赛药业有限责任公司 一种多簇连接子、其制备方法及应用

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3020585A1 (en) * 2016-04-11 2017-10-19 Arbutus Biopharma Corporation Targeted nucleic acid conjugate compositions
WO2024099316A1 (zh) * 2022-11-08 2024-05-16 南京明德新药研发有限公司 含七元杂环的四价缀合基团及其应用

Citations (4)

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CN108136206A (zh) * 2015-07-17 2018-06-08 阿克丘勒斯治疗公司 抗乙型肝炎病毒的组合物和药剂及其用途
CN109312342A (zh) * 2016-04-11 2019-02-05 阿布特斯生物制药公司 靶向核酸偶联物组合物
CN110741087A (zh) * 2017-04-11 2020-01-31 阿布特斯生物制药公司 靶向组合物
WO2020191207A1 (en) * 2019-03-20 2020-09-24 Arbutus Biopharma Corporation Therapeutic methods for treating hepatitis b

Family Cites Families (4)

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US20050222064A1 (en) * 2002-02-20 2005-10-06 Sirna Therapeutics, Inc. Polycationic compositions for cellular delivery of polynucleotides
EP2563922A1 (en) * 2010-04-26 2013-03-06 Marina Biotech, Inc. Nucleic acid compounds with conformationally restricted monomers and uses thereof
US11324820B2 (en) * 2017-04-18 2022-05-10 Alnylam Pharmaceuticals, Inc. Methods for the treatment of subjects having a hepatitis b virus (HBV) infection
JP7473472B2 (ja) * 2017-10-17 2024-04-23 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 アシアロ糖タンパク質受容体１の発現を阻害するためのＲＮＡｉ剤および組成物

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108136206A (zh) * 2015-07-17 2018-06-08 阿克丘勒斯治疗公司 抗乙型肝炎病毒的组合物和药剂及其用途
CN109312342A (zh) * 2016-04-11 2019-02-05 阿布特斯生物制药公司 靶向核酸偶联物组合物
CN110741087A (zh) * 2017-04-11 2020-01-31 阿布特斯生物制药公司 靶向组合物
WO2020191207A1 (en) * 2019-03-20 2020-09-24 Arbutus Biopharma Corporation Therapeutic methods for treating hepatitis b

Non-Patent Citations (1)

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Title
JESPER等: "A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects", 《NUCLEIC ACIDS RESEARCH》, vol. 38, no. 17, 7 May 2020 (2020-05-07) *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2026061476A1 (zh) * 2024-09-19 2026-03-26 长春金赛药业有限责任公司 一种多簇连接子、其制备方法及应用

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US20240052349A1 (en) 2024-02-15
MX2023005138A (es) 2023-06-23
JP2023548295A (ja) 2023-11-16
WO2022098990A1 (en) 2022-05-12
KR20230104652A (ko) 2023-07-10
AU2021376390A1 (en) 2023-06-22
CA3199757A1 (en) 2022-05-12
EP4240369A1 (en) 2023-09-13
IL302530A (en) 2023-07-01
EP4240369A4 (en) 2025-04-23
TW202233243A (zh) 2022-09-01
AU2021376390A9 (en) 2024-10-10

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