CA3042423A1 - Methods for preventing cardiovascular events through proprotein convertase subtilisin kexin 9 (pcsk9) protein reduction - Google Patents

Methods for preventing cardiovascular events through proprotein convertase subtilisin kexin 9 (pcsk9) protein reduction Download PDF

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Publication number
CA3042423A1
CA3042423A1 CA3042423A CA3042423A CA3042423A1 CA 3042423 A1 CA3042423 A1 CA 3042423A1 CA 3042423 A CA3042423 A CA 3042423A CA 3042423 A CA3042423 A CA 3042423A CA 3042423 A1 CA3042423 A1 CA 3042423A1
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subject
rnai agent
days
day
baseline
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English (en)
French (fr)
Inventor
Peter WIJNGAARD
David KALLEND
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Novartis AG
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The Medicines Co
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First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=60388127&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA3042423(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by The Medicines Co filed Critical The Medicines Co
Publication of CA3042423A1 publication Critical patent/CA3042423A1/en
Pending legal-status Critical Current

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    • 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
    • A61K48/005—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 'active' part of the composition delivered, i.e. the nucleic acid delivered
    • A61K48/0066—Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • 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
    • C12N15/1137—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 enzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C12Y304/21061—Kexin (3.4.21.61), i.e. proprotein convertase subtilisin/kexin type 9
    • 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
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • 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
    • C12N2310/322—2'-R Modification
    • 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
    • C12N2310/351—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
    • C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
    • C12N2310/3521—Methyl
    • 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)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Epidemiology (AREA)
  • Urology & Nephrology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Virology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Enzymes And Modification Thereof (AREA)
CA3042423A 2016-10-18 2017-10-18 Methods for preventing cardiovascular events through proprotein convertase subtilisin kexin 9 (pcsk9) protein reduction Pending CA3042423A1 (en)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US201662409816P 2016-10-18 2016-10-18
US62/409,816 2016-10-18
US201662422028P 2016-11-14 2016-11-14
US62/422,028 2016-11-14
US201762472525P 2017-03-16 2017-03-16
US62/472,525 2017-03-16
US201762550426P 2017-08-25 2017-08-25
US62/550,426 2017-08-25
PCT/US2017/057218 WO2018075658A1 (en) 2016-10-18 2017-10-18 Methods for preventing cardiovascular events through proprotein convertase subtilisin kexin 9 (pcsk9) protein reduction

Publications (1)

Publication Number Publication Date
CA3042423A1 true CA3042423A1 (en) 2018-04-26

Family

ID=60388127

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3042423A Pending CA3042423A1 (en) 2016-10-18 2017-10-18 Methods for preventing cardiovascular events through proprotein convertase subtilisin kexin 9 (pcsk9) protein reduction

Country Status (21)

Country Link
US (3) US20180104360A1 (enExample)
EP (2) EP3529360B1 (enExample)
JP (4) JP7181881B2 (enExample)
KR (3) KR20240067272A (enExample)
CN (4) CN119345221A (enExample)
AU (3) AU2017346879B2 (enExample)
CA (1) CA3042423A1 (enExample)
CL (1) CL2019001047A1 (enExample)
DK (1) DK3529360T3 (enExample)
ES (1) ES2982911T3 (enExample)
FI (1) FI3529360T3 (enExample)
HR (1) HRP20240930T1 (enExample)
HU (1) HUE067712T2 (enExample)
IL (1) IL266066A (enExample)
LT (1) LT3529360T (enExample)
MX (2) MX2019004573A (enExample)
PL (1) PL3529360T3 (enExample)
PT (1) PT3529360T (enExample)
RS (1) RS65725B1 (enExample)
SI (1) SI3529360T1 (enExample)
WO (1) WO2018075658A1 (enExample)

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR112015013105B1 (pt) 2012-12-05 2022-02-08 Alnylam Pharmaceuticals, Inc Agente de rnai de fita dupla capaz de inibir a expressão de pcsk9, seus usos, composição farmacêutica e método de inibição da expressão de pcsk9 em uma célula in vitro
EP3340994A1 (en) 2015-08-25 2018-07-04 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating a proprotein convertase subtilisin kexin (pcsk9) gene-associated disorder
HRP20240930T1 (hr) 2016-10-18 2024-10-11 Novartis Ag Postupci za prevenciju kardiovaskularnih događaja smanjenjem proteina proproteinske konvertaze suptilizin/keksin tipa 9 (pcsk9)
US11597744B2 (en) 2017-06-30 2023-03-07 Sirius Therapeutics, Inc. Chiral phosphoramidite auxiliaries and methods of their use
HRP20250277T1 (hr) 2017-12-01 2025-05-09 Suzhou Ribo Life Science Co., Ltd. Dvolančani oligonukleotid, sastav i konjugat koji sadrži dvolančani oligonukleotid, postupak njihove pripreme i upotreba
CN118291456A (zh) 2017-12-01 2024-07-05 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
WO2019105414A1 (zh) 2017-12-01 2019-06-06 苏州瑞博生物技术有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
CN110944675B9 (zh) 2017-12-01 2024-08-09 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
JP7360716B2 (ja) 2017-12-01 2023-10-13 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド 核酸、当該核酸を含む組成物および複合体ならびに調製方法と使用
CN110959011B (zh) 2017-12-29 2023-03-28 苏州瑞博生物技术股份有限公司 缀合物及其制备方法和用途
WO2020038377A1 (zh) 2018-08-21 2020-02-27 苏州瑞博生物技术有限公司 一种核酸、含有该核酸的药物组合物和缀合物及其用途
JP7376952B2 (ja) 2018-09-30 2023-11-09 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド ｓｉＲＮＡ複合体及びその調製方法と使用
JP7507495B2 (ja) 2018-12-28 2024-06-28 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド 核酸、当該核酸を含む組成物及び複合体ならびに調製方法と使用
WO2020150473A2 (en) 2019-01-18 2020-07-23 Dogma Therapeutics, Inc. Pcsk9 inhibitors and methods of use thereof
BR112021013924A2 (pt) 2019-01-18 2021-09-21 Astrazeneca Ab Inibidores de pcsk9 e métodos de uso do mesmo
CN113286888B (zh) * 2019-05-22 2023-12-22 苏州瑞博生物技术股份有限公司 核酸、药物组合物与缀合物及制备方法和用途
JP7610848B2 (ja) 2019-05-22 2025-01-09 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド 核酸、薬物組成物及び複合体ならびに調製方法と使用
CN113227376B (zh) 2019-05-22 2024-04-09 苏州瑞博生物技术股份有限公司 核酸、药物组合物与缀合物及制备方法和用途
CN113795582B (zh) 2019-05-24 2024-05-24 苏州瑞博生物技术股份有限公司 核酸、药物组合物与缀合物及制备方法和用途
US20230183694A1 (en) 2020-03-16 2023-06-15 Argonaute RNA Limited Antagonist of pcsk9
CN115572726A (zh) * 2021-06-21 2023-01-06 上海君实生物医药科技股份有限公司 一种抑制PCSK9基因表达的siRNA及其用途
WO2023241591A1 (zh) * 2022-06-14 2023-12-21 大睿生物医药科技(上海)有限公司 调控PCSK9基因活性的siRNA分子
JP2025531341A (ja) * 2022-09-19 2025-09-19 カイロンノヴァ （シャーメン） バイオファーマ カンパニー，リミテッド 炭水化物－オリゴヌクレオチド複合体、薬物組成物および治療への応用

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7605251B2 (en) * 2006-05-11 2009-10-20 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the PCSK9 gene
BR112015013105B1 (pt) * 2012-12-05 2022-02-08 Alnylam Pharmaceuticals, Inc Agente de rnai de fita dupla capaz de inibir a expressão de pcsk9, seus usos, composição farmacêutica e método de inibição da expressão de pcsk9 em uma célula in vitro
EP3340994A1 (en) * 2015-08-25 2018-07-04 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating a proprotein convertase subtilisin kexin (pcsk9) gene-associated disorder
HRP20240930T1 (hr) 2016-10-18 2024-10-11 Novartis Ag Postupci za prevenciju kardiovaskularnih događaja smanjenjem proteina proproteinske konvertaze suptilizin/keksin tipa 9 (pcsk9)

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Publication number Publication date
BR112019007843A2 (pt) 2019-10-01
SI3529360T1 (sl) 2024-08-30
EP4397311A2 (en) 2024-07-10
AU2026203584A1 (en) 2026-05-28
KR20190077411A (ko) 2019-07-03
JP2022109948A (ja) 2022-07-28
DK3529360T3 (da) 2024-07-15
AU2023263519B2 (en) 2026-02-12
CN119318663A (zh) 2025-01-17
JP2025016469A (ja) 2025-02-04
JP2019531357A (ja) 2019-10-31
US20260108631A1 (en) 2026-04-23
EP3529360B1 (en) 2024-04-17
EP4397311A3 (en) 2024-10-16
MX2024004495A (es) 2024-05-08
KR20240067272A (ko) 2024-05-16
PL3529360T3 (pl) 2024-08-26
JP7850215B2 (ja) 2026-04-22
AU2023263519A1 (en) 2023-12-07
EP3529360A1 (en) 2019-08-28
MX2019004573A (es) 2019-10-07
IL266066A (en) 2019-06-30
JP7566815B2 (ja) 2024-10-15
ES2982911T3 (es) 2024-10-18
AU2017346879B2 (en) 2023-11-30
PT3529360T (pt) 2024-07-12
FI3529360T3 (fi) 2024-07-11
LT3529360T (lt) 2024-07-25
US20180104360A1 (en) 2018-04-19
CN119700800A (zh) 2025-03-28
HUE067712T2 (hu) 2024-11-28
AU2017346879A1 (en) 2019-05-23
CN119345221A (zh) 2025-01-24
KR20250171391A (ko) 2025-12-08
JP2026062719A (ja) 2026-04-10
US20210093736A1 (en) 2021-04-01
HRP20240930T1 (hr) 2024-10-11
RS65725B1 (sr) 2024-08-30
CL2019001047A1 (es) 2020-05-08
JP7181881B2 (ja) 2022-12-01
WO2018075658A1 (en) 2018-04-26
CN110088283A (zh) 2019-08-02

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