WO2014205449A3 - Compounds and methods for modulating apolipoprotein c-iii expression for improving a diabetic profile - Google Patents

Compounds and methods for modulating apolipoprotein c-iii expression for improving a diabetic profile Download PDF

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Publication number
WO2014205449A3
WO2014205449A3 PCT/US2014/043723 US2014043723W WO2014205449A3 WO 2014205449 A3 WO2014205449 A3 WO 2014205449A3 US 2014043723 W US2014043723 W US 2014043723W WO 2014205449 A3 WO2014205449 A3 WO 2014205449A3
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WO
WIPO (PCT)
Prior art keywords
compounds
improving
methods
profile
iii expression
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/US2014/043723
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French (fr)
Other versions
WO2014205449A2 (en
Inventor
Rosanne M. Crooke
Veronica J. ALEXANDER
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ionis Pharmaceuticals Inc
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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
Priority to ES14813708T priority Critical patent/ES2778462T3/en
Priority to US14/900,320 priority patent/US9909124B2/en
Priority to EP14813708.6A priority patent/EP3011026B1/en
Priority to EP19217146.0A priority patent/EP3656386A1/en
Publication of WO2014205449A2 publication Critical patent/WO2014205449A2/en
Publication of WO2014205449A3 publication Critical patent/WO2014205449A3/en
Anticipated expiration legal-status Critical
Priority to US15/874,662 priority patent/US20180312840A1/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
    • 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
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • 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
    • 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
    • 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
    • C12N2310/31—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
    • C12N2310/323—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
    • C12N2310/33—Chemical structure of the base
    • C12N2310/334—Modified C
    • C12N2310/3341—5-Methylcytosine
    • 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 ===---===

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Epidemiology (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Diabetes (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (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)

Abstract

Provided herein are improved compounds, compositions and associated methods for reducing expression of ApoCIII mRNA and protein in a subject having, or at risk of having, diabetes. Also provided herein are compounds, compositions and associated methods improving peripheral insulin sensitivity, a lipid profile and a diabetes profile as well as reducing free fatty acids and intramyocellular triglyceride deposition.
PCT/US2014/043723 2013-06-21 2014-06-23 Compounds and methods for modulating apolipoprotein c-iii expression for improving a diabetic profile Ceased WO2014205449A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
ES14813708T ES2778462T3 (en) 2013-06-21 2014-06-23 Compounds and methods to modulate apolipoprotein C-III expression to improve a diabetic profile
US14/900,320 US9909124B2 (en) 2013-06-21 2014-06-23 Compounds and methods for modulating apolipoprotein C-III expression for improving a diabetic profile
EP14813708.6A EP3011026B1 (en) 2013-06-21 2014-06-23 Compounds and methods for modulating apolipoprotein c-iii expression for improving a diabetic profile
EP19217146.0A EP3656386A1 (en) 2013-06-21 2014-06-23 Compounds and methods for modulating apolipoprotein c-iii expression for improving a diabetic profile
US15/874,662 US20180312840A1 (en) 2013-06-21 2018-01-18 Compounds and methods for modulating apolipoprotein c-iii expression for improving a diabetic profile

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361838211P 2013-06-21 2013-06-21
US61/838,211 2013-06-21

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US14/900,320 A-371-Of-International US9909124B2 (en) 2013-06-21 2014-06-23 Compounds and methods for modulating apolipoprotein C-III expression for improving a diabetic profile
US15/874,662 Continuation US20180312840A1 (en) 2013-06-21 2018-01-18 Compounds and methods for modulating apolipoprotein c-iii expression for improving a diabetic profile

Publications (2)

Publication Number Publication Date
WO2014205449A2 WO2014205449A2 (en) 2014-12-24
WO2014205449A3 true WO2014205449A3 (en) 2015-04-23

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PCT/US2014/043723 Ceased WO2014205449A2 (en) 2013-06-21 2014-06-23 Compounds and methods for modulating apolipoprotein c-iii expression for improving a diabetic profile

Country Status (4)

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US (2) US9909124B2 (en)
EP (2) EP3011026B1 (en)
ES (1) ES2778462T3 (en)
WO (1) WO2014205449A2 (en)

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DK2992098T3 (en) 2013-05-01 2019-06-17 Ionis Pharmaceuticals Inc COMPOSITIONS AND METHODS FOR MODULATION OF HBV AND TTR EXPRESSION
EP3011026B1 (en) * 2013-06-21 2019-12-18 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating apolipoprotein c-iii expression for improving a diabetic profile
CN107405358A (en) * 2015-02-27 2017-11-28 Ionis制药公司 Modulation of apolipoprotein C‑III (APOCIII) expression in a lipodystrophy population
WO2016181409A1 (en) 2015-05-11 2016-11-17 Cadila Healthcare Limited Saroglitazar magnesium for the treatment of chylomicronemia syndrome -
CA3043768A1 (en) 2016-11-29 2018-06-07 PureTech Health LLC Exosomes for delivery of therapeutic agents
WO2020011745A2 (en) * 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers6
WO2020011744A2 (en) * 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers5
CN119564619A (en) * 2019-09-12 2025-03-07 阿奇维生命科学公司 Compositions comprising cytisine for treating and/or preventing addiction in subjects in need thereof
US20250304966A1 (en) 2020-12-23 2025-10-02 Argonaute RNA Limited Treatment of cardiovascular disease
WO2023041508A2 (en) 2021-09-14 2023-03-23 Argonaute RNA Limited Treatment of cardiovascular disease

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Also Published As

Publication number Publication date
US9909124B2 (en) 2018-03-06
ES2778462T3 (en) 2020-08-10
WO2014205449A2 (en) 2014-12-24
EP3011026A2 (en) 2016-04-27
US20160152974A1 (en) 2016-06-02
EP3011026A4 (en) 2017-02-22
US20180312840A1 (en) 2018-11-01
EP3656386A1 (en) 2020-05-27
EP3011026B1 (en) 2019-12-18

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