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WO2008011431A3 - Rna interference mediated inhibition of proprotein convertase subtilisin kexin 9 (pcsk9) gene expression using short interfering nucleic acid (sina) - Google Patents

Rna interference mediated inhibition of proprotein convertase subtilisin kexin 9 (pcsk9) gene expression using short interfering nucleic acid (sina) Download PDF

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Publication number
WO2008011431A3
WO2008011431A3 PCT/US2007/073723 US2007073723W WO2008011431A3 WO 2008011431 A3 WO2008011431 A3 WO 2008011431A3 US 2007073723 W US2007073723 W US 2007073723W WO 2008011431 A3 WO2008011431 A3 WO 2008011431A3
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WIPO (PCT)
Prior art keywords
nucleic acid
acid molecules
rna
gene expression
small nucleic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2007/073723
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French (fr)
Other versions
WO2008011431A2 (en
WO2008011431A8 (en
Inventor
James Mcswiggen
Vasant Jadhav
Narendra K Vaish
Roberto Guerciolini
Chandra Vargeese
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Sirna Therapeutics Inc
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Sirna Therapeutics Inc
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Publication date
Priority claimed from US11/487,788 external-priority patent/US20070173473A1/en
Application filed by Sirna Therapeutics Inc filed Critical Sirna Therapeutics Inc
Priority to JP2009520964A priority Critical patent/JP2010503382A/en
Priority to CA002658183A priority patent/CA2658183A1/en
Priority to AU2007275365A priority patent/AU2007275365A1/en
Priority to CN2007800269961A priority patent/CN102124107A/en
Priority to EP07813032A priority patent/EP2052079A2/en
Publication of WO2008011431A2 publication Critical patent/WO2008011431A2/en
Publication of WO2008011431A3 publication Critical patent/WO2008011431A3/en
Anticipated expiration legal-status Critical
Publication of WO2008011431A8 publication Critical patent/WO2008011431A8/en
Ceased legal-status Critical Current

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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
    • C12N15/113—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
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • A61P9/06—Antiarrhythmics
    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • 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
    • C12N2310/32—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

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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Cardiology (AREA)
  • Diabetes (AREA)
  • Heart & Thoracic Surgery (AREA)
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  • Biomedical Technology (AREA)
  • Obesity (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
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Abstract

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression and/or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and/or activity of genes involved in Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro- RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, and others that can inhibit the function of endogenous RNA molecules, such as endogenous micro-RNA (miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC), including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules and are useful, for example, in providing compositions to prevent, inhibit, or reduce metabolic diseases, traits and conditions, including but not limited to hyperlipidemia, hypercholesterolemia, cardiovascular disease, atherosclerosis, hypertension, diabetis (e.g., type I and/or type II diabetis), insulin resistance, obesity and/or other disease states, conditions, or traits that are associated with gene expression or activity in a subject or organism.
PCT/US2007/073723 2006-07-17 2007-07-17 Rna interference mediated inhibition of proprotein convertase subtilisin kexin 9 (pcsk9) gene expression using short interfering nucleic acid (sina) Ceased WO2008011431A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
JP2009520964A JP2010503382A (en) 2006-07-17 2007-07-17 RNA interference-mediated inhibition of proprotein convertase subtilisin kexin 9 (PCSK9) gene expression using small interfering nucleic acids (siNA)
CA002658183A CA2658183A1 (en) 2006-07-17 2007-07-17 Rna interference mediated inhibition of proprotein convertase subtilisin kexin 9 (pcsk9) gene expression using short interfering nucleic acid (sina)
AU2007275365A AU2007275365A1 (en) 2006-07-17 2007-07-17 RNA interference mediated inhibition of Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA)
CN2007800269961A CN102124107A (en) 2006-07-17 2007-07-17 RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA)
EP07813032A EP2052079A2 (en) 2006-07-17 2007-07-17 Rna interference mediated inhibition of proprotein convertase subtilisin kexin 9 (pcsk9) gene expression using short interfering nucleic acid (sina)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US11/487,788 US20070173473A1 (en) 2001-05-18 2006-07-17 RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA)
US11/487,788 2006-07-17
US86136906P 2006-11-28 2006-11-28
US60/861,369 2006-11-28

Publications (3)

Publication Number Publication Date
WO2008011431A2 WO2008011431A2 (en) 2008-01-24
WO2008011431A3 true WO2008011431A3 (en) 2008-07-17
WO2008011431A8 WO2008011431A8 (en) 2009-11-05

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PCT/US2007/073723 Ceased WO2008011431A2 (en) 2006-07-17 2007-07-17 Rna interference mediated inhibition of proprotein convertase subtilisin kexin 9 (pcsk9) gene expression using short interfering nucleic acid (sina)

Country Status (6)

Country Link
EP (1) EP2052079A2 (en)
JP (1) JP2010503382A (en)
CN (1) CN102124107A (en)
AU (1) AU2007275365A1 (en)
CA (1) CA2658183A1 (en)
WO (1) WO2008011431A2 (en)

Families Citing this family (60)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7514099B2 (en) 2005-02-14 2009-04-07 Sirna Therapeutics, Inc. Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules
US7935812B2 (en) 2002-02-20 2011-05-03 Merck Sharp & Dohme Corp. RNA interference mediated inhibition of hepatitis C virus (HCV) expression using short interfering nucleic acid (siNA)
US7404969B2 (en) 2005-02-14 2008-07-29 Sirna Therapeutics, Inc. Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules
NZ572666A (en) 2006-05-11 2010-11-26 Alnylam Pharmaceuticals Inc Compositions comprising double stranded rna and methods for inhibiting expression of the pcsk9 gene
EP2076597A2 (en) * 2006-10-09 2009-07-08 Santaris Pharma A/S Rna antagonist compounds for the modulation of pcsk9
EP2455471A3 (en) * 2006-11-27 2012-09-12 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US8093222B2 (en) 2006-11-27 2012-01-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
BRPI0907008A2 (en) * 2008-01-31 2015-07-07 Alnylam Pharmaceuticals Inc Optimized methods for dsrna release by targeting the pcsk9 gene
WO2009114475A2 (en) * 2008-03-09 2009-09-17 Intradigm Corporation Compositions comprising human pcsk9 and apolipoprotein b sirna and methods of use
US20110224280A1 (en) * 2008-04-16 2011-09-15 Niels Fisker Nielsen Pharmaceutical Composition Comprising Anti PCSK9 Oligomers
CA2635187A1 (en) 2008-06-05 2009-12-05 The Royal Institution For The Advancement Of Learning/Mcgill University Oligonucleotide duplexes and uses thereof
EP2331071A1 (en) 2008-09-05 2011-06-15 Institut National De La Sante Et De La Recherche Medicale Novel multimodular assembly useful for intracellular delivery
US9051567B2 (en) 2009-06-15 2015-06-09 Tekmira Pharmaceuticals Corporation Methods for increasing efficacy of lipid formulated siRNA
EA201270019A1 (en) 2009-06-15 2012-06-29 Элнилэм Фармасьютикалз, Инк. BENTROVAL RNA INCLUDED IN LIPID COMPOSITION AND WHICH IS THE PCSK9 GENE
EP2456870A1 (en) 2009-07-21 2012-05-30 Santaris Pharma A/S Antisense oligomers targeting pcsk9
WO2011038031A1 (en) 2009-09-22 2011-03-31 Alnylam Pharmaceuticals, Inc. Dual targeting sirna agents
EA026374B1 (en) * 2009-12-23 2017-04-28 Новартис Аг Lipids, lipid compositions, and methods of using them
JP6072766B2 (en) * 2011-04-08 2017-02-01 バイオ−ラッド ラボラトリーズ インコーポレーティッド PCR reaction mixture with reduced non-specific activity
JP2015502931A (en) * 2011-11-18 2015-01-29 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Ａｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． Modified RNAi agent
JP6002382B2 (en) * 2011-12-07 2016-10-05 株式会社バイオシンクタンク Gene expression inhibitor and inhibition method
ES2552371T3 (en) * 2012-05-25 2015-11-27 Zora Biosciences Oy Sensitive, effective and harmless biomarkers for the inhibition of Proprotein Convertase Subtilisin / Kexin type 9 (PCSK9)
KR102096014B1 (en) * 2012-12-05 2020-04-03 알닐람 파마슈티칼스 인코포레이티드 PCSK9 iRNA COMPOSITIONS AND METHODS OF USE THEREOF
WO2014207232A1 (en) 2013-06-27 2014-12-31 Santaris Pharma A/S Antisense oligomers and conjugates targeting pcsk9
US9045548B1 (en) 2014-07-15 2015-06-02 Kymab Limited Precision Medicine by targeting rare human PCSK9 variants for cholesterol treatment
US9023359B1 (en) 2014-07-15 2015-05-05 Kymab Limited Targeting rare human PCSK9 variants for cholesterol treatment
FR3014695A1 (en) * 2013-12-17 2015-06-19 Kymab Ltd
US8883157B1 (en) 2013-12-17 2014-11-11 Kymab Limited Targeting rare human PCSK9 variants for cholesterol treatment
US9914769B2 (en) 2014-07-15 2018-03-13 Kymab Limited Precision medicine for cholesterol treatment
US9034332B1 (en) 2014-07-15 2015-05-19 Kymab Limited Precision medicine by targeting rare human PCSK9 variants for cholesterol treatment
US9051378B1 (en) 2014-07-15 2015-06-09 Kymab Limited Targeting rare human PCSK9 variants for cholesterol treatment
US9139648B1 (en) 2014-07-15 2015-09-22 Kymab Limited Precision medicine by targeting human NAV1.9 variants for treatment of pain
GB2537614A (en) * 2015-04-20 2016-10-26 Heart Biotech Ltd Formulations for inhibition of PCSK9 for the treatment of hypercholesterolemia
KR20250107273A (en) * 2015-05-06 2025-07-11 알닐람 파마슈티칼스 인코포레이티드 Factor XII (Hageman Factor) (F12), KALLIKREIN B, PLASMA (FLETCHER FACTOR) 1 (KLKB1), and Kininogen 1 (KNG1) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
EA201890571A1 (en) 2015-08-25 2018-10-31 Элнилэм Фармасьютикалз, Инк. METHODS AND COMPOSITIONS FOR THE TREATMENT OF VIOLATION ASSOCIATED WITH THE PROTROTYNCONVERTASE GENE SUBTILYSINE / CEXINOUS TYPE (PCSK9)
EP3409779A4 (en) * 2016-01-26 2019-07-03 Nissan Chemical Corporation MONOCATERARY OLIGONUCLEOTIDE
CN117757794A (en) * 2016-03-07 2024-03-26 美国政府(由卫生和人类服务部的部长所代表) Micrornas and methods of use thereof
CA3019498A1 (en) * 2016-04-05 2017-10-12 Universite De Strasbourg Intra-droplet surface engineering to capture a molecular target
US11260134B2 (en) 2016-09-29 2022-03-01 National University Corporation Tokyo Medical And Dental University Double-stranded nucleic acid complex having overhang
JP7461886B2 (en) * 2017-11-13 2024-04-04 サイレンス・セラピューティクス・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング Nucleic acids containing phosphorodithioate bonds for suppressing expression of target genes
CN110997917B (en) 2017-12-01 2024-04-09 苏州瑞博生物技术股份有限公司 Nucleic acid, composition containing nucleic acid, conjugate, preparation method and application
CN110945130B (en) 2017-12-01 2024-04-09 苏州瑞博生物技术股份有限公司 Nucleic acid, composition and conjugate containing the nucleic acid, preparation method and use thereof
AU2018374219C1 (en) 2017-12-01 2023-05-11 Suzhou Ribo Life Science Co., Ltd. Double-stranded oligonucleotide, composition and conjugate comprising double-stranded oligonucleotide, preparation method therefor and use thereof
CN110945132B (en) 2017-12-01 2024-04-05 苏州瑞博生物技术股份有限公司 Nucleic acid, composition and conjugate containing the nucleic acid, preparation method and use thereof
EP3718572B1 (en) 2017-12-01 2024-07-31 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, composition and conjugate containing nucleic acid, preparation method and use
EP3677679A4 (en) * 2017-12-26 2020-12-02 Guangzhou Ribobio Co., Ltd. Sirna molecule inhibiting pcsk9 gene expression and application thereof
CN109957567B (en) * 2017-12-26 2022-09-23 阿格纳生物制药有限公司 siRNA molecule for inhibiting PCSK9 gene expression and application thereof
CN109957565B (en) * 2017-12-26 2023-04-07 广州市锐博生物科技有限公司 Modified siRNA molecule and application thereof
JP7436030B2 (en) 2017-12-29 2024-02-21 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 Complexes and their preparation and use
MX2020011006A (en) * 2018-04-18 2021-01-20 Dicerna Pharmaceuticals Inc Pcsk9 targeting oligonucleotides for treating hypercholesterolemia and related conditions.
EP3842534A4 (en) 2018-08-21 2022-07-06 Suzhou Ribo Life Science Co., Ltd. NUCLEIC ACID, PHARMACEUTICAL COMPOSITION AND CONJUGATE WITH NUCLEIC ACID AND THEIR USE
EP3862024A4 (en) 2018-09-30 2022-08-17 Suzhou Ribo Life Science Co., Ltd. Sirna conjugate, preparation method therefor and use thereof
CN109666727B (en) * 2018-12-29 2020-11-06 中国药科大学 Use of a microRNA with high activity to inhibit PCSK9 expression
CN116889627A (en) * 2019-03-20 2023-10-17 雷杰纳荣制药公司 Treating elevated lipid levels with sterol regulatory element binding transcription factor 1 (SREBF1) inhibitors
EP3974530A4 (en) * 2019-05-22 2023-07-12 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition, conjugate, preparation method, and use
US20220290156A1 (en) * 2019-08-27 2022-09-15 Sanofi Compositions and methods for inhibiting pcsk9
US20230183694A1 (en) 2020-03-16 2023-06-15 Argonaute RNA Limited Antagonist of pcsk9
WO2023284763A1 (en) * 2021-07-16 2023-01-19 苏州瑞博生物技术股份有限公司 Double-stranded oligonucleotide, composition and conjugate containing double-stranded oligonucleotide, and preparation methods and uses
EP4402263A2 (en) * 2021-09-14 2024-07-24 Argonaute Rna Limited Treatment of cardiovascular disease
WO2024104416A1 (en) * 2022-11-17 2024-05-23 北京福元医药股份有限公司 Sirna for inhibiting expression of scap gene, conjugate thereof, pharmaceutical composition thereof, and use thereof
WO2024228030A2 (en) * 2023-05-04 2024-11-07 Argonaute RNA Limited Dual silencing

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005014782A2 (en) * 2003-06-13 2005-02-17 Alnylam Europe Ag., Double-stranded ribonucleic acid with increased effectiveness in an organism
US20060148743A1 (en) * 2001-05-18 2006-07-06 Vasant Jadhav RNA interference mediated inhibition of histone deacetylase (HDAC) gene expression using short interfering nucleic acid (siNA)
WO2007030937A2 (en) * 2005-09-16 2007-03-22 Institut De Recherches Cliniques De Montreal/I.R.C.M. Screening proteinase modulators using a chimeric protein and ski-i proprotein convertase substrates and inhibitors
US20070173473A1 (en) * 2001-05-18 2007-07-26 Sirna Therapeutics, Inc. RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA)
WO2007131237A2 (en) * 2006-05-05 2007-11-15 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of ptp1b

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060148743A1 (en) * 2001-05-18 2006-07-06 Vasant Jadhav RNA interference mediated inhibition of histone deacetylase (HDAC) gene expression using short interfering nucleic acid (siNA)
US20070173473A1 (en) * 2001-05-18 2007-07-26 Sirna Therapeutics, Inc. RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA)
WO2005014782A2 (en) * 2003-06-13 2005-02-17 Alnylam Europe Ag., Double-stranded ribonucleic acid with increased effectiveness in an organism
WO2007030937A2 (en) * 2005-09-16 2007-03-22 Institut De Recherches Cliniques De Montreal/I.R.C.M. Screening proteinase modulators using a chimeric protein and ski-i proprotein convertase substrates and inhibitors
WO2007131237A2 (en) * 2006-05-05 2007-11-15 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of ptp1b

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BENJANNET SUZANNE ET AL: "NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol.", THE JOURNAL OF BIOLOGICAL CHEMISTRY 19 NOV 2004, vol. 279, no. 47, 19 November 2004 (2004-11-19), pages 48865 - 48875, XP002480952, ISSN: 0021-9258 *
LALANNE FLORENT ET AL: "Wild-type PCSK9 inhibits LDL clearance but does not affect apoB-containing lipoprotein production in mouse and cultured cells.", JOURNAL OF LIPID RESEARCH JUN 2005, vol. 46, no. 6, June 2005 (2005-06-01), pages 1312 - 1319, XP002478032, ISSN: 0022-2275 *

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