CA2380205A1 - Novel bicyclonucleoside analogues - Google Patents

Novel bicyclonucleoside analogues Download PDF

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Publication number
CA2380205A1
CA2380205A1 CA002380205A CA2380205A CA2380205A1 CA 2380205 A1 CA2380205 A1 CA 2380205A1 CA 002380205 A CA002380205 A CA 002380205A CA 2380205 A CA2380205 A CA 2380205A CA 2380205 A1 CA2380205 A1 CA 2380205A1
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CA
Canada
Prior art keywords
group
analogues
alpha
novel bicyclonucleoside
hydroxy
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Granted
Application number
CA002380205A
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French (fr)
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CA2380205C (en
Inventor
Takeshi Imanishi
Satoshi Obika
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Sankyo Co Ltd
Original Assignee
Sankyo Company, Limited
Takeshi Imanishi
Satoshi Obika
Daiichi Sankyo Company, Limited
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Publication of CA2380205A1 publication Critical patent/CA2380205A1/en
Application granted granted Critical
Publication of CA2380205C publication Critical patent/CA2380205C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16—Purine radicals
    • 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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

This invention provides novel bicyclonucleoside analogues which exhibit anti-AIDS activity and intermediates to produce oligonucleotide analogues which have anti-sense or anti-gene activity as well as in vivo stability.
The present invention is compounds of the following formula (1) or their pharmaceutically acceptable salts.

(see formula I) R1 represents a hydrogen atom or protecting group for a hydroxy group, R2 represents an azido group or an optionally protected amino group or the like, B represents a purin-9-yl or a 2-oxo-1,2-dihydropyrimidin-1-yl group which are optionally substituted with substituents selected from .alpha. group shown below.
(.alpha. group) halogen atom, alkyl group having 1-6 carbon atoms, hydroxy group, mercapto group, amino group, and the like.
CA002380205A 1999-07-22 2000-07-21 Novel bicyclonucleoside analogues Expired - Fee Related CA2380205C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP20717099 1999-07-22
JP11/207170 1999-07-22
PCT/JP2000/004902 WO2001007455A1 (en) 1999-07-22 2000-07-21 Novel bicyclonucleoside analogues

Publications (2)

Publication Number Publication Date
CA2380205A1 true CA2380205A1 (en) 2001-02-01
CA2380205C CA2380205C (en) 2009-03-17

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
CA002380205A Expired - Fee Related CA2380205C (en) 1999-07-22 2000-07-21 Novel bicyclonucleoside analogues

Country Status (24)

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US (2) US7217805B2 (en)
EP (1) EP1201678B1 (en)
JP (1) JP4151751B2 (en)
KR (1) KR20020092894A (en)
CN (1) CN1376161A (en)
AT (1) ATE277066T1 (en)
AU (1) AU766656B2 (en)
BR (1) BR0012646A (en)
CA (1) CA2380205C (en)
CZ (1) CZ2002132A3 (en)
DE (1) DE60014104T2 (en)
DK (1) DK1201678T3 (en)
ES (1) ES2226891T3 (en)
HK (1) HK1044776A1 (en)
HU (1) HUP0202812A3 (en)
IL (1) IL147595A0 (en)
MX (1) MXPA02000826A (en)
NO (1) NO20020305L (en)
NZ (1) NZ516653A (en)
PL (1) PL352682A1 (en)
PT (1) PT1201678E (en)
RU (1) RU2227143C2 (en)
WO (1) WO2001007455A1 (en)
ZA (1) ZA200200398B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9464106B2 (en) 2002-10-21 2016-10-11 Exiqon A/S Oligonucleotides useful for detecting and analyzing nucleic acids of interest

Families Citing this family (130)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1273478C (en) 1999-02-12 2006-09-06 三共株式会社 Novel nucleosides and oligonucleotide analogues
JP4148662B2 (en) * 2000-08-10 2008-09-10 第一三共株式会社 Nucleic acid reagents and pharmaceuticals containing nucleosides and oligonucleotide analogs
WO2002020543A2 (en) * 2000-09-07 2002-03-14 Avecia Biotechnology Inc. Synthons for oligonucleotide synthesis
KR20020069627A (en) * 2001-02-27 2002-09-05 동부한농화학 주식회사 Phosphorothioate oligonucleotides containing modified nucleotides with six-membered azasugars and use for aids therapy thereof
AU2003211953A1 (en) * 2002-02-13 2003-09-04 Takeshi Imanishi Nucleoside analogues and oligonucleotide derivative comprising nucleotide analogue thereof
DK1639130T3 (en) 2003-06-20 2012-07-09 Exiqon As PROBLEMS, LIBRARIES AND KITS FOR ANALYSIS OF NUCLEIC ACID MIXTURES AND METHODS FOR BUILDING THESE
US8415100B2 (en) 2003-08-14 2013-04-09 Case Western Reserve University Methods and compositions for detecting gastrointestinal and other cancers
EP1660683B1 (en) * 2003-08-14 2017-04-19 Case Western Reserve University Methods and compositions for detecting colon cancers
US7906639B2 (en) * 2003-11-07 2011-03-15 Sankyo Company, Limited Oligonucleotides having a 2′-O,4′-C-ethylene nucleotide in the third position of the 3′-end
US8192937B2 (en) 2004-04-07 2012-06-05 Exiqon A/S Methods for quantification of microRNAs and small interfering RNAs
WO2006069584A2 (en) 2004-12-29 2006-07-06 Exiqon A/S NOVEL OLIGONUCLEOTIDE COMPOSITIONS AND PROBE SEQUENCES USEFUL FOR DETECTION AND ANALYSIS OF microRNAs AND THEIR TARGET mRNAs
US20070065840A1 (en) * 2005-03-23 2007-03-22 Irena Naguibneva Novel oligonucleotide compositions and probe sequences useful for detection and analysis of microRNAS and their target mRNAS
ES2516815T3 (en) 2006-01-27 2014-10-31 Isis Pharmaceuticals, Inc. Analogs of bicyclic nucleic acids modified at position 6
US8586554B2 (en) 2006-05-05 2013-11-19 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of PTP1B
EP2505650A1 (en) 2006-05-05 2012-10-03 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of PCSK9
DK2066684T3 (en) * 2006-05-11 2012-10-22 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
EP2090665A2 (en) 2006-10-20 2009-08-19 Exiqon A/S Novel human microRNAs associated with cancer
US8188255B2 (en) 2006-10-20 2012-05-29 Exiqon A/S Human microRNAs associated with cancer
US8084437B2 (en) * 2006-11-27 2011-12-27 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US8093222B2 (en) 2006-11-27 2012-01-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
WO2008074328A2 (en) * 2006-12-21 2008-06-26 Exiqon A/S Microrna target site blocking oligos and uses thereof
EP3536788A1 (en) 2006-12-21 2019-09-11 QIAGEN GmbH Microrna target site blocking oligos and uses thereof
EP2118118B1 (en) 2007-01-19 2017-09-27 Exiqon A/S Mediated cellular delivery of lna oligonucleotides
AU2008260277C1 (en) 2007-05-30 2014-04-17 Isis Pharmaceuticals, Inc. N-substituted-aminomethylene bridged bicyclic nucleic acid analogs
DK2173760T4 (en) 2007-06-08 2016-02-08 Isis Pharmaceuticals Inc Carbocyclic bicyclic nukleinsyreanaloge
EP2176280B2 (en) * 2007-07-05 2015-06-24 Isis Pharmaceuticals, Inc. 6-disubstituted bicyclic nucleic acid analogs
WO2009067647A1 (en) * 2007-11-21 2009-05-28 Isis Pharmaceuticals, Inc. Carbocyclic alpha-l-bicyclic nucleic acid analogs
EP4053546A1 (en) 2007-12-06 2022-09-07 Genalyte, Inc. Device and method for performing label-free monitoring of processes.
US8530640B2 (en) * 2008-02-07 2013-09-10 Isis Pharmaceuticals, Inc. Bicyclic cyclohexitol nucleic acid analogs
WO2009124238A1 (en) * 2008-04-04 2009-10-08 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising neutrally linked terminal bicyclic nucleosides
EP2297322A1 (en) 2008-06-04 2011-03-23 The Board of Regents of The University of Texas System Modulation of gene expression through endogenous small rna targeting of gene promoters
AU2009276763B2 (en) 2008-07-29 2015-07-16 The Board Of Regents Of The University Of Texas Sytem Selective inhibition of polyglutamine protein expression
US8501805B2 (en) * 2008-09-24 2013-08-06 Isis Pharmaceuticals, Inc. Substituted alpha-L-bicyclic nucleosides
WO2010062627A2 (en) 2008-10-27 2010-06-03 Genalyte Inc. Biosensors based on optical probing and sensing
EP2421972A2 (en) 2009-04-24 2012-02-29 The Board of Regents of The University of Texas System Modulation of gene expression using oligomers that target gene regions downstream of 3' untranslated regions
WO2010150789A1 (en) 2009-06-23 2010-12-29 武田薬品工業株式会社 Method for synthesizing nucleic acid
WO2011010706A1 (en) 2009-07-23 2011-01-27 武田薬品工業株式会社 Fgf21 cis-element binding substance
EP2462153B1 (en) 2009-08-06 2015-07-29 Isis Pharmaceuticals, Inc. Bicyclic cyclohexose nucleic acid analogs
WO2011053994A1 (en) 2009-11-02 2011-05-05 Alnylam Pharmaceuticals, Inc. Modulation of ldl receptor gene expression with double-stranded rnas targeting the ldl receptor gene promoter
WO2011085102A1 (en) 2010-01-11 2011-07-14 Isis Pharmaceuticals, Inc. Base modified bicyclic nucleosides and oligomeric compounds prepared therefrom
US9574191B2 (en) 2010-02-03 2017-02-21 The Board Of Regents Of The University Of Texas System Selective inhibition of polyglutamine protein expression
WO2011115818A1 (en) 2010-03-17 2011-09-22 Isis Pharmaceuticals, Inc. 5'-substituted bicyclic nucleosides and oligomeric compounds prepared therefrom
EP3173419A1 (en) 2010-04-28 2017-05-31 Ionis Pharmaceuticals, Inc. Modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom
ES2465948T3 (en) 2010-04-30 2014-06-09 Exiqon A/S In situ hybridization procedure and buffer
WO2011156278A1 (en) 2010-06-07 2011-12-15 Isis Pharmaceuticals, Inc. Bicyclic nucleosides and oligomeric compounds prepared therefrom
WO2012061778A2 (en) 2010-11-05 2012-05-10 Genalyte, Inc. Optical analyte detection systems and methods of use
EP3067421B1 (en) 2011-02-08 2018-10-10 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
EP2495336B8 (en) 2011-03-04 2014-07-23 Roche Diagnostics GmbH A new type of universal probes for the detection of genomic variants
EP4269584A3 (en) 2011-08-11 2024-03-27 Ionis Pharmaceuticals, Inc. Selective antisense compounds and uses thereof
WO2013090457A2 (en) 2011-12-12 2013-06-20 Oncoimmunin Inc. In vivo delivery of oligonucleotides
EP3907506A1 (en) 2012-03-12 2021-11-10 The Board of Trustees of the University of Illinois Optical analyte detection systems with magnetic enhancement and methods of their use
AU2013202595B2 (en) 2012-03-30 2016-04-21 Biogen Ma Inc. Methods for modulating Tau expression for reducing seizure and modifying a neurodegenerative syndrome
WO2013154799A1 (en) 2012-04-09 2013-10-17 Isis Pharmaceuticals, Inc. Tricyclic nucleosides and oligomeric compounds prepared therefrom
US9221864B2 (en) 2012-04-09 2015-12-29 Isis Pharmaceuticals, Inc. Tricyclic nucleic acid analogs
US9914922B2 (en) 2012-04-20 2018-03-13 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
EP2897633B1 (en) 2012-09-18 2020-01-01 UTI Limited Partnership Treatment of pain by inhibition of usp5 de-ubiquitinase
US10377789B2 (en) * 2012-09-21 2019-08-13 Osaka University Oligonucleotide and artificial nucleoside having guanidine bridge
JP6242336B2 (en) 2012-09-28 2017-12-06 株式会社Ｂｎａ BNA clamp method
US9695418B2 (en) 2012-10-11 2017-07-04 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleosides and uses thereof
US9029335B2 (en) 2012-10-16 2015-05-12 Isis Pharmaceuticals, Inc. Substituted 2′-thio-bicyclic nucleosides and oligomeric compounds prepared therefrom
WO2014066239A1 (en) 2012-10-22 2014-05-01 Idenix Pharmaceuticals, Inc. 2',4'-bridged nucleosides for hcv infection
EP2929050A1 (en) 2012-12-10 2015-10-14 AdvanDx, Inc. Use of probes for mass spectrometric identification of microorganisms or cells and associated conditions of interest
US20150337002A1 (en) * 2013-01-15 2015-11-26 Shionogi & Co., Ltd. Nucleoside and nucleotide having sulfonamide structure
US10086093B2 (en) 2013-02-28 2018-10-02 The General Hospital Corporation miRNA profiling compositions and methods of use
US10398661B2 (en) 2013-02-28 2019-09-03 The Board Of Regents Of The University Of Texas System Methods for classifying a cancer as susceptible to TMEPAI-directed therapies and treating such cancers
US9273349B2 (en) 2013-03-14 2016-03-01 Affymetrix, Inc. Detection of nucleic acids
MX2015012621A (en) 2013-03-14 2016-05-31 Ionis Pharmaceuticals Inc Compositions and methods for modulating tau expression.
RU2686080C2 (en) 2013-05-01 2019-04-24 Ионис Фармасьютикалз, Инк. Compositions and methods
TWI702046B (en) 2013-07-19 2020-08-21 美商Ionis製藥公司 Compositions for modulating tau expression
US11162096B2 (en) 2013-10-14 2021-11-02 Ionis Pharmaceuticals, Inc Methods for modulating expression of C9ORF72 antisense transcript
PT3757214T (en) 2014-04-01 2022-08-26 Biogen Ma Inc Compositions for modulating sod-1 expression
EP3137476B1 (en) 2014-04-28 2019-10-09 Ionis Pharmaceuticals, Inc. Linkage modified oligomeric compounds
PE20170010A1 (en) 2014-05-01 2017-03-04 Ionis Pharmaceuticals Inc COMPOSITIONS AND METHODS TO MODULATE THE EXPRESSION OF THE COMPLEMENT FACTOR B
GB201410693D0 (en) 2014-06-16 2014-07-30 Univ Southampton Splicing modulation
WO2016054615A2 (en) 2014-10-03 2016-04-07 Cold Spring Harbor Laboratory Targeted augmentation of nuclear gene output
EP3234141A4 (en) 2014-12-18 2018-06-20 Alnylam Pharmaceuticals, Inc. Reversir tm compounds
US9688707B2 (en) 2014-12-30 2017-06-27 Ionis Pharmaceuticals, Inc. Bicyclic morpholino compounds and oligomeric compounds prepared therefrom
WO2016112132A1 (en) 2015-01-06 2016-07-14 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of c9orf72 antisense transcript
WO2016167780A1 (en) 2015-04-16 2016-10-20 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of c9orf72 antisense transcript
CA3205381A1 (en) 2015-07-17 2017-01-26 Alnylam Pharmaceuticals, Inc. Multi-targeted single entity conjugates
SG11201802870RA (en) 2015-10-09 2018-05-30 Univ Southampton Modulation of gene expression and screening for deregulated protein expression
US11058709B1 (en) 2015-12-04 2021-07-13 Ionis Pharmaceuticals, Inc. Methods of treating breast cancer
US11096956B2 (en) 2015-12-14 2021-08-24 Stoke Therapeutics, Inc. Antisense oligomers and uses thereof
WO2017106377A1 (en) 2015-12-14 2017-06-22 Cold Spring Harbor Laboratory Antisense oligomers for treatment of autosomal dominant mental retardation-5 and dravet syndrome
WO2017111137A1 (en) * 2015-12-22 2017-06-29 味の素株式会社 Oligonucleotide manufacturing method
WO2017161168A1 (en) 2016-03-16 2017-09-21 Ionis Pharmaceuticals, Inc. Modulation of dyrk1b expression
WO2017161172A1 (en) 2016-03-16 2017-09-21 Ionis Pharmaceuticals, Inc. Methods of modulating keap1
EP3471781A4 (en) 2016-06-17 2020-05-06 Ionis Pharmaceuticals, Inc. Modulation of gys1 expression
US11098077B2 (en) 2016-07-05 2021-08-24 Chinook Therapeutics, Inc. Locked nucleic acid cyclic dinucleotide compounds and uses thereof
KR20240010761A (en) 2016-09-14 2024-01-24 얀센 바이오파마, 인크. Modified oligonucleotides and methods of use
JOP20190065A1 (en) 2016-09-29 2019-03-28 Ionis Pharmaceuticals Inc Compounds and methods for reducing tau expression
EP3548620A4 (en) 2016-12-02 2020-07-22 Cold Spring Harbor Laboratory Modulation of lnc05 expression
WO2018165564A1 (en) 2017-03-09 2018-09-13 Ionis Pharmaceuticals, Inc. Morpholino modified oligomeric compounds
US11197884B2 (en) 2017-08-18 2021-12-14 Ionis Pharmaceuticals, Inc. Modulation of the notch signaling pathway for treatment of respiratory disorders
GB2599884B (en) 2017-08-25 2022-08-31 Stoke Therapeutics Inc Antisense oligomers for treatment of conditions and diseases
WO2019051173A1 (en) 2017-09-08 2019-03-14 Ionis Pharmaceuticals, Inc. Modulators of smad7 expression
MX2020002885A (en) 2017-09-14 2020-10-01 Janssen Biopharma Inc Galnac derivatives.
AU2019233612A1 (en) 2018-03-13 2020-09-10 Janssen Pharmaceutica Nv Modified oligonucleotides for use in treatment of tauopathies
AU2019266207A1 (en) 2018-05-07 2020-12-17 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
EP3856907A1 (en) 2018-09-28 2021-08-04 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases
TW202028222A (en) 2018-11-14 2020-08-01 美商Ionis製藥公司 Modulators of foxp3 expression
EP3880821A4 (en) 2018-11-15 2023-01-25 Ionis Pharmaceuticals, Inc. Modulators of irf5 expression
JP2022519532A (en) 2019-01-31 2022-03-24 アイオーニス ファーマシューティカルズ， インコーポレーテッド Modulator of YAP1 expression
MX2021010152A (en) 2019-02-27 2021-09-14 Ionis Pharmaceuticals Inc Modulators of malat1 expression.
CA3136676A1 (en) 2019-05-03 2020-11-12 Dicerna Pharmaceuticals, Inc. Double-stranded nucleic acid inhibitor molecules with shortened sense strands
US20220211743A1 (en) 2019-05-17 2022-07-07 Alnylam Pharmaceuticals, Inc. Oral delivery of oligonucleotides
EP3956450A4 (en) 2019-07-26 2022-11-16 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating gfap
WO2021030778A1 (en) 2019-08-15 2021-02-18 Ionis Pharmaceuticals, Inc. Linkage modified oligomeric compounds and uses thereof
JP2023500681A (en) 2019-11-06 2023-01-10 アルニラム ファーマスーティカルズ インコーポレイテッド extrahepatic delivery
EP4055165A1 (en) 2019-11-06 2022-09-14 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases
KR20220161436A (en) 2020-03-31 2022-12-06 얀센 바이오파마, 인코퍼레이트. Synthesis of oligonucleotides and related compounds
US20230287410A1 (en) 2020-05-11 2023-09-14 Stoke Therapeutics, Inc. Opa1 antisense oligomers for treatment of conditions and diseases
WO2022147214A2 (en) 2020-12-31 2022-07-07 Alnylam Pharmaceuticals, Inc. Cyclic-disulfide modified phosphate based oligonucleotide prodrugs
EP4271695A2 (en) 2020-12-31 2023-11-08 Alnylam Pharmaceuticals, Inc. 2'-modified nucleoside based oligonucleotide prodrugs
KR20240009393A (en) 2021-03-31 2024-01-22 엔트라다 테라퓨틱스, 인크. Cyclic cell penetrating peptide
WO2022240721A1 (en) 2021-05-10 2022-11-17 Entrada Therapeutics, Inc. Compositions and methods for modulating interferon regulatory factor-5 (irf-5) activity
WO2022240760A2 (en) 2021-05-10 2022-11-17 Entrada Therapeutics, Inc. COMPOSITIONS AND METHODS FOR MODULATING mRNA SPLICING
AU2022271873A1 (en) 2021-05-10 2024-01-04 Entrada Therapeutics, Inc. Compositions and methods for intracellular therapeutics
IL309001A (en) 2021-06-23 2024-02-01 Entrada Therapeutics Inc Antisense compounds and methods for targeting cug repeats
WO2023283403A2 (en) 2021-07-09 2023-01-12 Alnylam Pharmaceuticals, Inc. Bis-rnai compounds for cns delivery
KR20240036041A (en) 2021-07-21 2024-03-19 알닐람 파마슈티칼스 인코포레이티드 Metabolic Disorder-Associated Target Gene iRNA Composition and Methods of Using Same
CA3229661A1 (en) 2021-09-01 2023-03-09 Xiang Li Compounds and methods for skipping exon 44 in duchenne muscular dystrophy
WO2023064530A1 (en) 2021-10-15 2023-04-20 Alnylam Pharmaceuticals, Inc. Extra-hepatic delivery irna compositions and methods of use thereof
WO2023220744A2 (en) 2022-05-13 2023-11-16 Alnylam Pharmaceuticals, Inc. Single-stranded loop oligonucleotides
WO2024006999A2 (en) 2022-06-30 2024-01-04 Alnylam Pharmaceuticals, Inc. Cyclic-disulfide modified phosphate based oligonucleotide prodrugs
WO2024040041A1 (en) 2022-08-15 2024-02-22 Dicerna Pharmaceuticals, Inc. Regulation of activity of rnai molecules
WO2024039776A2 (en) 2022-08-18 2024-02-22 Alnylam Pharmaceuticals, Inc. Universal non-targeting sirna compositions and methods of use thereof
WO2024073732A1 (en) 2022-09-30 2024-04-04 Alnylam Pharmaceuticals, Inc. Modified double-stranded rna agents

Family Cites Families (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3687808A (en) * 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
NZ209840A (en) * 1983-10-17 1988-11-29 Kaji Akira A method of inhibiting viral propagation by hybridising dna with the viral rna thus blocking its action
US4806463A (en) * 1986-05-23 1989-02-21 Worcester Foundation For Experimental Biology Inhibition of HTLV-III by exogenous oligonucleotides
US5194428A (en) * 1986-05-23 1993-03-16 Worcester Foundation For Experimental Biology Inhibition of influenza virus replication by oligonucleotide phosphorothioates
US5004810A (en) * 1988-09-30 1991-04-02 Schering Corporation Antiviral oligomers
US5457189A (en) * 1989-12-04 1995-10-10 Isis Pharmaceuticals Antisense oligonucleotide inhibition of papillomavirus
US5620963A (en) * 1991-10-15 1997-04-15 Isis Pharmaceuticals, Inc. Oligonucleotides for modulating protein kinase C having phosphorothioate linkages of high chiral purity
US5591623A (en) * 1990-08-14 1997-01-07 Isis Pharmaceuticals, Inc. Oligonucleotide modulation of cell adhesion
US5248670A (en) * 1990-02-26 1993-09-28 Isis Pharmaceuticals, Inc. Antisense oligonucleotides for inhibiting herpesviruses
US5514577A (en) * 1990-02-26 1996-05-07 Isis Pharmaceuticals, Inc. Oligonucleotide therapies for modulating the effects of herpes viruses
US5166195A (en) * 1990-05-11 1992-11-24 Isis Pharmaceuticals, Inc. Antisense inhibitors of the human immunodeficiency virus phosphorothioate oligonucleotides
WO1992003454A1 (en) * 1990-08-14 1992-03-05 Isis Pharmaceuticals, Inc. Inhibition of influenza virus type a, ann arbor strain h2n2 by antisense oligonucleotides
US6111094A (en) * 1990-08-14 2000-08-29 Isis Pharmaceuticals Inc. Enhanced antisense modulation of ICAM-1
US5591720A (en) * 1990-08-16 1997-01-07 Isis Pharmaceuticals, Inc. Oligonucleotides for modulating the effects of cytomegalovirus infections
US5442049A (en) * 1992-11-19 1995-08-15 Isis Pharmaceuticals, Inc. Oligonucleotides for modulating the effects of cytomegalovirus infections
US5691461A (en) * 1990-08-16 1997-11-25 Isis Pharmaceuticals, Inc. Oligonucleotides inhibiting candida germ tube formation
US5242906A (en) * 1991-04-22 1993-09-07 University Of North Carolina At Chapel Hill Antisense oligonucleotides against Epstein-Barr virus
WO1994008003A1 (en) 1991-06-14 1994-04-14 Isis Pharmaceuticals, Inc. ANTISENSE OLIGONUCLEOTIDE INHIBITION OF THE ras GENE
US5582986A (en) * 1991-06-14 1996-12-10 Isis Pharmaceuticals, Inc. Antisense oligonucleotide inhibition of the ras gene
CA2111472A1 (en) * 1991-06-14 1992-12-23 Brett P. Monia Antisense oligonucleotide inhibition of the ras gene
US5661134A (en) * 1991-10-15 1997-08-26 Isis Pharmaceuticals, Inc. Oligonucleotides for modulating Ha-ras or Ki-ras having phosphorothioate linkages of high chiral purity
US5607923A (en) * 1991-10-15 1997-03-04 Isis Pharmaceuticals, Inc. Oligonucleotides for modulating cytomegalovirus having phosphorothioate linkages of high chiral purity
US5681747A (en) * 1992-03-16 1997-10-28 Isis Pharmaceuticals, Inc. Nucleic acid sequences encoding protein kinase C and antisense inhibition of expression thereof
US5523389A (en) * 1992-09-29 1996-06-04 Isis Pharmaceuticals, Inc. Inhibitors of human immunodeficiency virus
US5985558A (en) * 1997-04-14 1999-11-16 Isis Pharmaceuticals Inc. Antisense oligonucleotide compositions and methods for the inibition of c-Jun and c-Fos
PT820483E (en) 1995-04-07 2001-03-30 Mogens Havsteen Jakobsen METHOD OF IMMOBILIZATION OF PHOTOCHEMICALS OF LIGANDS USING QUINONES
US5684143A (en) 1996-02-21 1997-11-04 Lynx Therapeutics, Inc. Oligo-2'-fluoronucleotide N3'->P5' phosphoramidates
US6127533A (en) * 1997-02-14 2000-10-03 Isis Pharmaceuticals, Inc. 2'-O-aminooxy-modified oligonucleotides
JP3756313B2 (en) * 1997-03-07 2006-03-15 武 今西 Novel bicyclonucleosides and oligonucleotide analogues
US5877309A (en) * 1997-08-13 1999-03-02 Isis Pharmaceuticals, Inc. Antisense oligonucleotides against JNK
US7572582B2 (en) * 1997-09-12 2009-08-11 Exiqon A/S Oligonucleotide analogues
US6794499B2 (en) * 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
EP1557424A1 (en) 1997-09-12 2005-07-27 Exiqon A/S Bi-cyclic nucleoside, nucleotide and oligonucleoide analogues
US5955443A (en) * 1998-03-19 1999-09-21 Isis Pharmaceuticals Inc. Antisense modulation of PECAM-1
CN1273478C (en) * 1999-02-12 2006-09-06 三共株式会社 Novel nucleosides and oligonucleotide analogues

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9464106B2 (en) 2002-10-21 2016-10-11 Exiqon A/S Oligonucleotides useful for detecting and analyzing nucleic acids of interest

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