WO2020011745A3 - Antisense oligonucleotides targeting cers6 - Google Patents

Antisense oligonucleotides targeting cers6 Download PDF

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Publication number
WO2020011745A3
WO2020011745A3 PCT/EP2019/068323 EP2019068323W WO2020011745A3 WO 2020011745 A3 WO2020011745 A3 WO 2020011745A3 EP 2019068323 W EP2019068323 W EP 2019068323W WO 2020011745 A3 WO2020011745 A3 WO 2020011745A3
Authority
WO
WIPO (PCT)
Prior art keywords
cers6
antisense oligonucleotides
oligonucleotides targeting
diabetes
expression
Prior art date
Application number
PCT/EP2019/068323
Other languages
French (fr)
Other versions
WO2020011745A2 (en
Inventor
Marie Wirkström LINDHOLM
Steffen Schmidt
Original Assignee
Roche Innovation Center Copenhagen A/S
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 Roche Innovation Center Copenhagen A/S filed Critical Roche Innovation Center Copenhagen A/S
Publication of WO2020011745A2 publication Critical patent/WO2020011745A2/en
Publication of WO2020011745A3 publication Critical patent/WO2020011745A3/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
    • 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
    • A61P35/00—Antineoplastic agents

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

Abstract

The present invention relates to antisense LNA oligonucleotides (oligomers) complementary to CERS6 pre-mRNA exon and intron sequences, which are capable of inhibiting the expression of CERS6 protein. Inhibition of CERS6 expression is beneficial for a range of medical disorders including obesity, insulin resistance, diabetes such as type 2 diabetes, atherosclerosis, cardiomyopathy, opioid drug addiction and multiple sclerosis.
PCT/EP2019/068323 2018-07-11 2019-07-09 Antisense oligonucleotides targeting cers6 WO2020011745A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP18182925.0 2018-07-11
EP18182925 2018-07-11

Publications (2)

Publication Number Publication Date
WO2020011745A2 WO2020011745A2 (en) 2020-01-16
WO2020011745A3 true WO2020011745A3 (en) 2020-02-20

Family

ID=62916546

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2019/068323 WO2020011745A2 (en) 2018-07-11 2019-07-09 Antisense oligonucleotides targeting cers6

Country Status (1)

Country Link
WO (1) WO2020011745A2 (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008006007A2 (en) * 2006-07-03 2008-01-10 Columbia University Defective cystic fibrosis transduction regulator (cftr) causes increased sphingolipid synthesis
WO2013011135A1 (en) * 2011-07-20 2013-01-24 Johann Wolfgang Goethe-Universität Frankfurt Ceramide c16-cer and cers6 in the treatment and diagnosis of multiple sclerosis (ms)
WO2014205449A2 (en) * 2013-06-21 2014-12-24 Isis Pharmaceuticals, Inc. Compounds and methods for modulating apolipoprotein c-iii expression for improving a diabetic profile

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU1039397A (en) 1995-11-22 1997-06-27 Johns Hopkins University, The Ligands to enhance cellular uptake of biomolecules
JP3756313B2 (en) 1997-03-07 2006-03-15 武 今西 Novel bicyclonucleosides and oligonucleotide analogues
AU9063398A (en) 1997-09-12 1999-04-05 Exiqon A/S Oligonucleotide analogues
NZ513402A (en) 1999-02-12 2003-06-30 Sankyo Co Novel nucleosides and oligonucleotide analogues
CN102180924A (en) 1999-05-04 2011-09-14 桑塔里斯制药公司 L-ribo-LNA analogues
US6617442B1 (en) 1999-09-30 2003-09-09 Isis Pharmaceuticals, Inc. Human Rnase H1 and oligonucleotide compositions thereof
ES2607471T3 (en) 2002-11-18 2017-03-31 Roche Innovation Center Copenhagen A/S Antisense design
WO2007031091A2 (en) 2005-09-15 2007-03-22 Santaris Pharma A/S Rna antagonist compounds for the modulation of p21 ras expression
ES2516815T3 (en) 2006-01-27 2014-10-31 Isis Pharmaceuticals, Inc. Analogs of bicyclic nucleic acids modified at position 6
AU2007249349B2 (en) 2006-05-11 2012-03-08 Isis Pharmaceuticals, Inc. 5'-Modified bicyclic nucleic acid analogs
US7666854B2 (en) 2006-05-11 2010-02-23 Isis Pharmaceuticals, Inc. Bis-modified bicyclic nucleic acid analogs
ES2526295T5 (en) 2006-10-18 2021-05-04 Ionis Pharmaceuticals Inc Antisense compounds
US20100086543A1 (en) 2007-04-02 2010-04-08 Saint Louis University Compositions and methods for treating conditions associated with ceramide biosynthesis
AU2008260277C1 (en) 2007-05-30 2014-04-17 Isis Pharmaceuticals, Inc. N-substituted-aminomethylene bridged bicyclic nucleic acid analogs
EP2173760B2 (en) 2007-06-08 2015-11-04 Isis Pharmaceuticals, Inc. Carbocyclic bicyclic nucleic acid analogs
CN101796062B (en) 2007-07-05 2014-07-30 Isis制药公司 6-disubstituted bicyclic nucleic acid analogs
US8546556B2 (en) 2007-11-21 2013-10-01 Isis Pharmaceuticals, Inc Carbocyclic alpha-L-bicyclic nucleic acid analogs
WO2009126933A2 (en) 2008-04-11 2009-10-15 Alnylam Pharmaceuticals, Inc. Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
EP2356129B1 (en) 2008-09-24 2013-04-03 Isis Pharmaceuticals, Inc. Substituted alpha-l-bicyclic nucleosides
US9012421B2 (en) 2009-08-06 2015-04-21 Isis Pharmaceuticals, Inc. Bicyclic cyclohexose nucleic acid analogs
EP2580228B1 (en) 2010-06-08 2016-03-23 Ionis Pharmaceuticals, Inc. Substituted 2'-amino and 2'-thio-bicyclic nucleosides and oligomeric compounds prepared therefrom
CA2816155C (en) 2010-12-17 2020-10-27 Arrowhead Research Corporation Galactose cluster-pharmacokinetic modulator targeting moiety for sirna
ES2605990T3 (en) 2010-12-29 2017-03-17 F. Hoffmann-La Roche Ag Small molecule conjugates for intracellular administration of nucleic acids
US10017764B2 (en) 2011-02-08 2018-07-10 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
WO2013022966A1 (en) 2011-08-11 2013-02-14 Isis Pharmaceuticals, Inc. Linkage modified gapped oligomeric compounds and uses thereof
WO2013154798A1 (en) 2012-04-09 2013-10-17 Isis Pharmaceuticals, Inc. Tricyclic nucleic acid analogs
MX363068B (en) 2012-11-15 2019-03-07 Roche Innovation Ct Copenhagen As Oligonucleotide conjugates.
CA2893801A1 (en) 2013-01-30 2014-08-07 F. Hoffmann-La Roche Ag Lna oligonucleotide carbohydrate conjugates
PL2992009T3 (en) 2013-05-01 2020-11-30 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating apolipoprotein (a) expression
NZ630921A (en) 2013-05-01 2017-12-22 Regulus Therapeutics Inc Compounds and methods for enhanced cellular uptake
CA2935426C (en) 2014-01-30 2023-07-25 F. Hoffmann-La Roche Ag Polyoligomer compound with biocleavable conjugates for reducing or inhibiting expression of a nucleic acid target

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008006007A2 (en) * 2006-07-03 2008-01-10 Columbia University Defective cystic fibrosis transduction regulator (cftr) causes increased sphingolipid synthesis
WO2013011135A1 (en) * 2011-07-20 2013-01-24 Johann Wolfgang Goethe-Universität Frankfurt Ceramide c16-cer and cers6 in the treatment and diagnosis of multiple sclerosis (ms)
WO2014205449A2 (en) * 2013-06-21 2014-12-24 Isis Pharmaceuticals, Inc. Compounds and methods for modulating apolipoprotein c-iii expression for improving a diabetic profile

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
HAMMERSCHMIDT PHILIPP ET AL: "CerS6-Derived Sphingolipids Interact with Mff and Promote Mitochondrial Fragmentation in Obesity", CELL, vol. 177, no. 6, 18 April 2010 (2010-04-18), pages 1536, XP085702148, ISSN: 0092-8674, DOI: 10.1016/J.CELL.2019.05.008 *
MESICEK J ET AL: "Ceramide synthases 2, 5, and 6 confer distinct roles in radiation-induced apoptosis in HeLa cells", CELLULAR SIGNALLING, ELSEVIER SCIENCE LTD, GB, vol. 22, no. 9, 1 September 2010 (2010-09-01), pages 1300 - 1307, XP027087695, ISSN: 0898-6568, [retrieved on 20100614] *
WEGNER MARTHE-SUSANNA ET AL: "The enigma of ceramide synthase regulation in mammalian cells", PROGRESS IN LIPID RESEARCH, PERGAMON PRESS, PARIS, FR, vol. 63, 13 May 2016 (2016-05-13), pages 93 - 119, XP029672393, ISSN: 0163-7827, DOI: 10.1016/J.PLIPRES.2016.03.006 *

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Publication number Publication date
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