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WO2009148605A3 - Methods for treating hypercholesterolemia - Google Patents

Methods for treating hypercholesterolemia Download PDF

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Publication number
WO2009148605A3
WO2009148605A3 PCT/US2009/003398 US2009003398W WO2009148605A3 WO 2009148605 A3 WO2009148605 A3 WO 2009148605A3 US 2009003398 W US2009003398 W US 2009003398W WO 2009148605 A3 WO2009148605 A3 WO 2009148605A3
Authority
WO
WIPO (PCT)
Prior art keywords
methods
antisense compounds
antisense
disclosed
individual
Prior art date
Application number
PCT/US2009/003398
Other languages
French (fr)
Other versions
WO2009148605A2 (en
Inventor
Susan M. Freier
Rosanne M. Crooke
Mark J. Graham
Kristina L. Lemonidis
Sanjay Bhanot
Diane Tribble
Andrew T. Watt
Original Assignee
Isis Pharmaceuticals, Inc.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Isis Pharmaceuticals, Inc. filed Critical Isis Pharmaceuticals, Inc.
Publication of WO2009148605A2 publication Critical patent/WO2009148605A2/en
Publication of WO2009148605A3 publication Critical patent/WO2009148605A3/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
    • C12N15/113—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
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C12N9/6454—Dibasic site splicing serine proteases, e.g. kexin (3.4.21.61); furin (3.4.21.75) and other proprotein convertases
    • 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
    • C12N2310/11—Antisense
    • 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
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
    • 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
    • C12N2310/341—Gapmers, i.e. of the type ===---===
    • 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
    • C12N2310/3525—MOE, methoxyethoxy

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Virology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Disclosed herein are antisense compounds and methods for decreasing LDL-C in an individual having elevated LDL-C. Additionally disclosed are antisense compounds and methods for treating, preventing, or ameliorating hypercholesterolemia and/or atherosclerosis. Further disclosed are antisense compounds and methods for decreasing coronary heart disease risk. Such methods include administering to an individual in need of treatment an antisense compound targeted to a PCSK9 nucleic acid. The antisense compounds administered include gapmer antisense oligonucleotides.
PCT/US2009/003398 2008-06-04 2009-06-04 Methods for treating hypercholesterolemia WO2009148605A2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US5870708P 2008-06-04 2008-06-04
US61/058,707 2008-06-04
US5916908P 2008-06-05 2008-06-05
US61/059,169 2008-06-05

Publications (2)

Publication Number Publication Date
WO2009148605A2 WO2009148605A2 (en) 2009-12-10
WO2009148605A3 true WO2009148605A3 (en) 2010-04-01

Family

ID=41203920

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2009/003398 WO2009148605A2 (en) 2008-06-04 2009-06-04 Methods for treating hypercholesterolemia

Country Status (1)

Country Link
WO (1) WO2009148605A2 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9127276B2 (en) 2013-05-01 2015-09-08 Isis Pharmaceuticals, Inc. Conjugated antisense compounds and their use

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8093222B2 (en) 2006-11-27 2012-01-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
JP2010510807A (en) 2006-11-27 2010-04-08 アイシス ファーマシューティカルズ， インコーポレーテッド Methods for treating hypercholesterolemia
CN102282155B (en) 2008-12-02 2017-06-09 日本波涛生命科学公司 The synthetic method of the nucleic acid of phosphorus atoms modification
CA2767253A1 (en) 2009-07-06 2011-01-13 Ontorii, Inc. Novel nucleic acid prodrugs and methods of use thereof
US8563528B2 (en) 2009-07-21 2013-10-22 Santaris Pharma A/S Antisense oligomers targeting PCSK9
WO2011085271A2 (en) 2010-01-08 2011-07-14 Isis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
EP2612914B1 (en) * 2010-08-31 2017-06-21 Osaka University Oligonucleotide, and therapeutic agent for dyslipidemia containing oligonucleotide as active ingredient
DK2620428T3 (en) 2010-09-24 2019-07-01 Wave Life Sciences Ltd Asymmetric help group
JP6128529B2 (en) 2011-07-19 2017-05-17 ウェイブ ライフ サイエンシズ リミテッドＷａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｌｔｄ． Methods for the synthesis of functionalized nucleic acids
KR101850319B1 (en) 2012-07-13 2018-04-20 웨이브 라이프 사이언시스 리미티드 Asymmetric auxiliary group
SG11201500243WA (en) 2012-07-13 2015-04-29 Shin Nippon Biomedical Lab Ltd Chiral nucleic acid adjuvant
CN112007045A (en) 2012-07-13 2020-12-01 波涛生命科学有限公司 Chiral control
NZ708171A (en) 2012-11-15 2019-11-29 Roche Innovation Ct Copenhagen As Oligonucleotide conjugates
DK2951305T3 (en) 2013-01-30 2018-10-29 Hoffmann La Roche LNA oligonucleotide KULHYDRATKONJUGATER
CN103314925A (en) * 2013-06-21 2013-09-25 四川大学华西医院 Preparation method of rhesus monkey type 2 diabetes model
US9879265B2 (en) * 2013-06-27 2018-01-30 Roche Innovation Center Copenhagen A/S Oligonucleotide conjugates
WO2015108048A1 (en) 2014-01-15 2015-07-23 株式会社新日本科学 Chiral nucleic acid adjuvant having antitumor effect and antitumor agent
EP3095461A4 (en) 2014-01-15 2017-08-23 Shin Nippon Biomedical Laboratories, Ltd. Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator
JPWO2015108046A1 (en) 2014-01-15 2017-03-23 株式会社新日本科学 Chiral nucleic acid adjuvant and antiallergic agent having antiallergic action
EP4137572A1 (en) 2014-01-16 2023-02-22 Wave Life Sciences Ltd. Chiral design
WO2015179693A1 (en) 2014-05-22 2015-11-26 Isis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
MA43072A (en) 2015-07-22 2018-05-30 Wave Life Sciences Ltd COMPOSITIONS OF OLIGONUCLEOTIDES AND RELATED PROCESSES
MA45270A (en) 2016-05-04 2017-11-09 Wave Life Sciences Ltd COMPOSITIONS OF OLIGONUCLEOTIDES AND RELATED PROCESSES
US11400161B2 (en) 2016-10-06 2022-08-02 Ionis Pharmaceuticals, Inc. Method of conjugating oligomeric compounds
WO2018102397A1 (en) 2016-11-29 2018-06-07 PureTech Health LLC Exosomes for delivery of therapeutic agents
JOP20190215A1 (en) * 2017-03-24 2019-09-19 Ionis Pharmaceuticals Inc Modulators of pcsk9 expression
CN106947825B (en) * 2017-04-25 2020-04-28 华南理工大学 SNP marker for origin (subgroup) identification of cynomolgus monkey and application thereof
JOP20190150A1 (en) 2018-06-21 2019-12-21 Merck Sharp & Dohme Pcsk9 antagonist compounds
US20230346773A1 (en) * 2020-07-01 2023-11-02 Min Chen Use of pcsk9 inhibitor in preparation of product for treating multiple diseases
CN113730593B (en) * 2021-08-02 2024-01-26 成都凌泰氪生物技术有限公司 A method for enhancing the sustained release ability of nucleic acid drugs
WO2024229020A2 (en) * 2023-05-01 2024-11-07 Chroma Medicine, Inc. Compositions and methods for epigenetic regulation of pcsk9 expression

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003011887A2 (en) * 2001-08-01 2003-02-13 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein b expression
WO2007131237A2 (en) * 2006-05-05 2007-11-15 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of ptp1b
WO2008043753A2 (en) * 2006-10-09 2008-04-17 Santaris Pharma A/S Rna antagonist compounds for the modulation of pcsk9
WO2008066776A2 (en) * 2006-11-27 2008-06-05 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003011887A2 (en) * 2001-08-01 2003-02-13 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein b expression
WO2007131237A2 (en) * 2006-05-05 2007-11-15 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of ptp1b
WO2008043753A2 (en) * 2006-10-09 2008-04-17 Santaris Pharma A/S Rna antagonist compounds for the modulation of pcsk9
WO2008066776A2 (en) * 2006-11-27 2008-06-05 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
GRAHAM MARK J ET AL: "Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice", JOURNAL OF LIPID RESEARCH, vol. 48, no. 4, April 2007 (2007-04-01), pages 763 - 767, XP002565438, ISSN: 0022-2275 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9127276B2 (en) 2013-05-01 2015-09-08 Isis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
US9181549B2 (en) 2013-05-01 2015-11-10 Isis Pharmaceuticals, Inc. Conjugated antisense compounds and their use

Also Published As

Publication number Publication date
WO2009148605A2 (en) 2009-12-10

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