WO2003004602A3 - Nuclease resistant chimeric oligonucleotides - Google Patents

Nuclease resistant chimeric oligonucleotides Download PDF

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Publication number
WO2003004602A3
WO2003004602A3 PCT/US2002/020934 US0220934W WO03004602A3 WO 2003004602 A3 WO2003004602 A3 WO 2003004602A3 US 0220934 W US0220934 W US 0220934W WO 03004602 A3 WO03004602 A3 WO 03004602A3
Authority
WO
WIPO (PCT)
Prior art keywords
oligomeric compounds
chimeric oligonucleotides
nuclease resistant
oligomeric
nuclease
Prior art date
Application number
PCT/US2002/020934
Other languages
French (fr)
Other versions
WO2003004602A2 (en
Inventor
Muthiah Manoharan
Martin A Maier
Thazha P Prakash
Kallanthottathil Gopala Rajeev
Original Assignee
Isis Pharmaceuticals Inc
Muthiah Manoharan
Martin A Maier
Thazha P Prakash
Kallanthottathil Gopala Rajeev
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
Priority claimed from US09/996,292 external-priority patent/US20030158403A1/en
Priority claimed from US10/013,295 external-priority patent/US20030175906A1/en
Application filed by Isis Pharmaceuticals Inc, Muthiah Manoharan, Martin A Maier, Thazha P Prakash, Kallanthottathil Gopala Rajeev filed Critical Isis Pharmaceuticals Inc
Priority to EP02746811A priority Critical patent/EP1499627A2/en
Priority to JP2003510761A priority patent/JP2005504020A/en
Priority to CA002452458A priority patent/CA2452458A1/en
Publication of WO2003004602A2 publication Critical patent/WO2003004602A2/en
Publication of WO2003004602A3 publication Critical patent/WO2003004602A3/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Saccharide Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to novel nuclease-resistant oligomeric compounds and to novel methods for increasing resistance of oligomeric compounds. In preferred embodiments of the invention, the oligomeric compounds comprise at least one modified nucleoside containing a modified sugar moiety at either the 3' or 5' terminus of the oligomeric compound, and further comprise at least one internucleoside linking group that is other than phosphodiester. Other preferred embodiments of the invention include methods of enhancing the nuclease resistance of oligomeric compounds comprising incorporating at least one modified nucleoside containing a modified sugar moiety at either the 3' or 5' terminus of an oligomeric compound.
PCT/US2002/020934 2001-07-03 2002-07-01 Nuclease resistant chimeric oligonucleotides WO2003004602A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP02746811A EP1499627A2 (en) 2001-07-03 2002-07-01 Nuclease resistant chimeric oligonucleotides
JP2003510761A JP2005504020A (en) 2001-07-03 2002-07-01 Nuclease resistant chimeric oligonucleotide
CA002452458A CA2452458A1 (en) 2001-07-03 2002-07-01 Nuclease resistant chimeric oligonucleotides

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US30268201P 2001-07-03 2001-07-03
US60/302,682 2001-07-03
US09/996,292 2001-11-28
US09/996,292 US20030158403A1 (en) 2001-07-03 2001-11-28 Nuclease resistant chimeric oligonucleotides
US10/013,295 2001-12-10
US10/013,295 US20030175906A1 (en) 2001-07-03 2001-12-10 Nuclease resistant chimeric oligonucleotides

Publications (2)

Publication Number Publication Date
WO2003004602A2 WO2003004602A2 (en) 2003-01-16
WO2003004602A3 true WO2003004602A3 (en) 2004-11-18

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2002/020934 WO2003004602A2 (en) 2001-07-03 2002-07-01 Nuclease resistant chimeric oligonucleotides

Country Status (4)

Country Link
EP (1) EP1499627A2 (en)
JP (1) JP2005504020A (en)
CA (1) CA2452458A1 (en)
WO (1) WO2003004602A2 (en)

Cited By (8)

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Publication number Priority date Publication date Assignee Title
US8846639B2 (en) 2008-04-04 2014-09-30 Isis Pharmaceutical, Inc. Oligomeric compounds comprising bicyclic nucleosides and having reduced toxicity
US9150606B2 (en) 2002-11-05 2015-10-06 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2'-modified nucleosides for use in gene modulation
US9175291B2 (en) 2012-10-11 2015-11-03 Isis Pharmaceuticals Inc. Modulation of androgen receptor expression
US9382540B2 (en) 2014-05-01 2016-07-05 Isis Pharmaceuticals, Inc Compositions and methods for modulating angiopoietin-like 3 expression
US9399774B2 (en) 2010-04-29 2016-07-26 Ionis Pharmaceuticals, Inc. Modulation of transthyretin expression
US9598693B2 (en) 2006-01-27 2017-03-21 Ionis Pharmaceuticals, Inc. Oligomeric compounds and compositions for the use in modulation of micrornas
US11851655B2 (en) 2013-05-01 2023-12-26 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating apolipoprotein (a) expression
US12129466B2 (en) 2019-03-29 2024-10-29 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating UBE3A-ATS

Families Citing this family (143)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9096636B2 (en) 1996-06-06 2015-08-04 Isis Pharmaceuticals, Inc. Chimeric oligomeric compounds and their use in gene modulation
US5898031A (en) 1996-06-06 1999-04-27 Isis Pharmaceuticals, Inc. Oligoribonucleotides for cleaving RNA
US7812149B2 (en) 1996-06-06 2010-10-12 Isis Pharmaceuticals, Inc. 2′-Fluoro substituted oligomeric compounds and compositions for use in gene modulations
US7098192B2 (en) 1999-04-08 2006-08-29 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of STAT3 expression
US20050019915A1 (en) 2001-06-21 2005-01-27 Bennett C. Frank Antisense modulation of superoxide dismutase 1, soluble expression
EP2221376B1 (en) 2001-06-21 2012-11-21 Isis Pharmaceuticals, Inc. Antisense modulation of superoxide dismutase 1, soluble expression
JP2005504020A (en) * 2001-07-03 2005-02-10 アイシス・ファーマシューティカルス・インコーポレーテッド Nuclease resistant chimeric oligonucleotide
US7425545B2 (en) 2001-07-25 2008-09-16 Isis Pharmaceuticals, Inc. Modulation of C-reactive protein expression
US9150605B2 (en) 2002-11-05 2015-10-06 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2′-modified nucleosides for use in gene modulation
AU2003290597A1 (en) 2002-11-05 2004-06-03 Isis Pharmaceuticals, Inc. Modified oligonucleotides for use in rna interference
JP4579911B2 (en) 2003-06-03 2010-11-10 アイシス・ファーマシューティカルズ・インコーポレイテッド Regulation of survivin expression
US7683036B2 (en) 2003-07-31 2010-03-23 Regulus Therapeutics Inc. Oligomeric compounds and compositions for use in modulation of small non-coding RNAs
US7825235B2 (en) 2003-08-18 2010-11-02 Isis Pharmaceuticals, Inc. Modulation of diacylglycerol acyltransferase 2 expression
CN100558893C (en) 2003-09-18 2009-11-11 Isis药物公司 The adjusting that eIF4E expresses
US8569474B2 (en) 2004-03-09 2013-10-29 Isis Pharmaceuticals, Inc. Double stranded constructs comprising one or more short strands hybridized to a longer strand
US8394947B2 (en) 2004-06-03 2013-03-12 Isis Pharmaceuticals, Inc. Positionally modified siRNA constructs
US7884086B2 (en) 2004-09-08 2011-02-08 Isis Pharmaceuticals, Inc. Conjugates for use in hepatocyte free uptake assays
EP1859040A2 (en) 2005-02-25 2007-11-28 Isis Pharmaceuticals, Inc. Compositions and their uses directed to il-4r alpha
US20090203893A1 (en) 2005-08-29 2009-08-13 Regulus Therapeutics, Llc Antisense compounds having enhanced anti-microrna activity
EP1931782B2 (en) 2005-08-29 2016-04-20 Regulus Therapeutics Inc Methods for use in modulating mir-122a
AU2007325767A1 (en) 2006-11-27 2008-06-05 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
EP2641971A1 (en) 2007-01-29 2013-09-25 Isis Pharmaceuticals, Inc. Compounds and methods for modulating protein expression
NZ580712A (en) 2007-05-22 2011-12-22 Marina Biotech Inc Hydroxymethyl substituted rna oligonucleotides and rna complexes containing acyclic monomers
CA2701128A1 (en) 2007-10-01 2009-04-09 Isis Pharmaceuticals, Inc. Antisense modulation of fibroblast growth factor receptor 4 expression
JP2010539978A (en) 2007-10-02 2010-12-24 アムジェン インコーポレイテッド Increased erythropoietin using nucleic acids that can hybridize to micro-RNA and its precursors
CN103898110A (en) * 2007-10-03 2014-07-02 夸克制药公司 Novel sirna structures
CA2705316A1 (en) 2007-11-09 2009-05-14 Isis Pharmaceuticals, Inc. Modulation of factor 7 expression
EP2294181A4 (en) 2008-05-22 2013-04-24 Isis Pharmaceuticals Inc Modulation of smrt expression
WO2009143390A2 (en) 2008-05-22 2009-11-26 Isis Pharmaceuticals, Inc. Methods for modulating expression of rbp4
EP3335715A3 (en) 2008-10-15 2018-08-08 Ionis Pharmaceuticals, Inc. Modulation of factor 11 expression
WO2010048585A2 (en) 2008-10-24 2010-04-29 Isis Pharmaceuticals, Inc. Oligomeric compounds and methods
CA2744987C (en) 2008-12-02 2018-01-16 Chiralgen, Ltd. Method for the synthesis of phosphorus atom modified nucleic acids
SG171879A1 (en) 2008-12-03 2011-07-28 Marina Biotech Inc Usirna complexes
EP2393825A2 (en) 2009-02-06 2011-12-14 Isis Pharmaceuticals, Inc. Oligomeric compounds and methods
WO2010107838A1 (en) 2009-03-16 2010-09-23 Isis Pharmaceuticals, Inc. Targeting apolipoprotein b for the reduction of apolipoprotein c-iii
AU2010262862C1 (en) 2009-06-17 2020-04-30 Biogen Ma Inc. Compositions and methods for modulation of SMN2 splicing in a subject
CA2767253A1 (en) 2009-07-06 2011-01-13 Ontorii, Inc. Novel nucleic acid prodrugs and methods of use thereof
KR102279458B1 (en) 2009-09-11 2021-07-21 아이오니스 파마수티컬즈, 인코포레이티드 Modulation of huntingtin expression
DK2488532T3 (en) 2009-10-16 2018-08-13 Melinta Therapeutics Inc ANTIMICROBIAL COMPOUNDS AND PROCEDURES FOR PREPARING AND USING THE SAME
CN102725274A (en) 2009-10-16 2012-10-10 Rib-X制药公司 Antimicrobial compounds and methods of making and using the same
TWI612048B (en) * 2009-10-16 2018-01-21 梅林塔療法公司 Antimicrobial compounds and methods of making and using the same
US8653047B2 (en) 2010-01-08 2014-02-18 Isis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
US9006198B2 (en) 2010-02-08 2015-04-14 Isis Pharmaceuticals, Inc. Selective reduction of allelic variants
EP3561060A1 (en) 2010-02-08 2019-10-30 Ionis Pharmaceuticals, Inc. Selective reduction of allelic variants
WO2011139911A2 (en) 2010-04-29 2011-11-10 Isis Pharmaceuticals, Inc. Lipid formulated single stranded rna
KR20180105730A (en) 2010-07-19 2018-09-28 아이오니스 파마수티컬즈, 인코포레이티드 Modulation of dystrophia myotonica-protein kinase (dmpk) expression
EP2620428B1 (en) 2010-09-24 2019-05-22 Wave Life Sciences Ltd. Asymmetric auxiliary group
WO2012064758A2 (en) 2010-11-08 2012-05-18 Isis Pharmaceuticals, Inc. Methods for modulating factor 12 expression
EP3521451A1 (en) 2010-11-17 2019-08-07 Ionis Pharmaceuticals, Inc. Modulation of alpha synuclein expression
GB201021867D0 (en) * 2010-12-23 2011-02-02 Mologen Ag Non-coding immunomodulatory DNA construct
WO2012135736A2 (en) 2011-04-01 2012-10-04 Isis Pharmaceuticals, Inc. Modulation of signal transducer and activator of transcription 3 (stat3) expression
EP3505528B1 (en) 2011-04-21 2020-11-25 Ionis Pharmaceuticals, Inc. Modulation of hepatitis b virus (hbv) expression
EP2701713B1 (en) 2011-04-27 2018-02-07 Ionis Pharmaceuticals, Inc. Modulation of apolipoprotein ciii (apociii) expression
AU2012267546B2 (en) 2011-06-10 2015-12-24 Ionis Pharmaceuticals, Inc. Methods for modulating kallikrein (KLKB1) expression
US9187749B2 (en) 2011-06-10 2015-11-17 Isis Pharmaceuticals, Inc. Methods for modulating factor 12 expression
JP6043347B2 (en) 2011-06-16 2016-12-14 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Ionis Pharmaceuticals,Inc. Antisense regulation of fibroblast growth factor receptor 4 expression
US9322021B2 (en) 2011-06-29 2016-04-26 Ionis Pharmaceuticals, Inc. Methods for modulating kallikrein (KLKB1) expression
EP3248982A1 (en) 2011-07-19 2017-11-29 Wave Life Sciences Ltd. Thiosulfonate reagents for the synthesis of functionalized nucleic acids
US20140303235A1 (en) 2011-08-11 2014-10-09 Isis Pharmaceuticals, Inc. Linkage modified gapped oligomeric compounds and uses thereof
CN103814132B (en) 2011-09-20 2018-06-05 苏州瑞博生物技术有限公司 The antisense of GCGR expression is adjusted
CA2853373A1 (en) 2011-10-25 2013-05-02 Isis Pharmaceuticals, Inc. Antisense modulation of gccr expression
ES2761343T3 (en) 2011-11-07 2020-05-19 Ionis Pharmaceuticals Inc Modulation of TMPRSS6 expression
CA2895077A1 (en) 2011-12-12 2013-06-20 Beverly Packard In vivo delivery of oligonucleotides
CA2859729C (en) 2011-12-22 2021-03-09 Isis Pharmaceuticals, Inc. Methods for modulating metastasis-associated-in-lung-adenocarcinoma-transcript-1(malat-1) expression
WO2013120003A1 (en) 2012-02-08 2013-08-15 Isis Pharmaceuticals, Inc. Modulation of rna by repeat targeting
AU2013202595B2 (en) 2012-03-30 2016-04-21 Biogen Ma Inc. Methods for modulating Tau expression for reducing seizure and modifying a neurodegenerative syndrome
US9574193B2 (en) 2012-05-17 2017-02-21 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein (a) expression
US20160002624A1 (en) 2012-05-17 2016-01-07 Isis Pharmaceuticals, Inc. Antisense oligonucleotide compositions
US9518261B2 (en) 2012-05-22 2016-12-13 Ionis Pharmaceuticals, Inc. Modulation of enhancer RNA mediated gene expression
KR102657351B1 (en) 2012-05-24 2024-04-16 아이오니스 파마수티컬즈, 인코포레이티드 Methods and compositions for modulating apolipoprotein (a) expression
ES2688831T3 (en) 2012-06-25 2018-11-07 Ionis Pharmaceuticals, Inc. UBE3A-ATS expression modulation
SG11201500239VA (en) 2012-07-13 2015-03-30 Wave Life Sciences Japan Asymmetric auxiliary group
EP4219516A3 (en) 2012-07-13 2024-01-10 Wave Life Sciences Ltd. Chiral control
WO2014010718A1 (en) 2012-07-13 2014-01-16 株式会社新日本科学 Chiral nucleic acid adjuvant
EP3693460A1 (en) 2012-07-27 2020-08-12 Ionis Pharmaceuticals, Inc. Modulation of renin-angiotensin system (ras) related diseases by angiotensinogen
ES2907254T3 (en) 2012-10-11 2022-04-22 Ionis Pharmaceuticals Inc A modified antisense compound for use in the treatment of Kennedy disease
RU2020127664A (en) 2012-10-15 2020-09-17 Ионис Фармасьютикалз, Инк. COMPOSITIONS FOR C9ORF72 GENE EXPRESSION MODULATION
FI2906696T4 (en) 2012-10-15 2023-03-18 Methods for modulating c9orf72 expression
US10577604B2 (en) 2012-10-15 2020-03-03 Ionis Pharmaceuticals, Inc. Methods for monitoring C9ORF72 expression
EP3483273A1 (en) 2012-10-31 2019-05-15 Ionis Pharmaceuticals, Inc. Cancer treatment
RU2018121529A (en) 2013-02-14 2019-03-06 Ионис Фармасьютикалз, Инк. MODULATION OF EXPRESSION OF APOLIPOPROTEIN C-III (AroCIII) IN PEOPLE WITH LIPOPROTEINLIPASE DEFICIENCY (LPLD)
CN111254145A (en) 2013-03-14 2020-06-09 Ionis制药公司 Compositions and methods for modulating TAU expression
US10590412B2 (en) 2013-04-19 2020-03-17 Ionis Pharmaceuticals, Inc. Compositions and methods for modulation nucleic acids through nonsense mediated decay
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
US20170073689A1 (en) 2013-07-02 2017-03-16 Ionis Pharmaceuticals, Inc. Modulators of growth hormone receptor
TWI772856B (en) 2013-07-19 2022-08-01 美商百健Ma公司 Compositions for modulating tau expression
TW201536329A (en) 2013-08-09 2015-10-01 Isis Pharmaceuticals Inc Compounds and methods for modulation of dystrophia myotonica-protein kinase (DMPK) expression
BR112016004093A2 (en) 2013-08-28 2017-10-17 Ionis Pharmaceuticals Inc modulation of pre-kallikrein expression (pkk)
EP3038623A4 (en) 2013-09-09 2017-04-19 Melinta Therapeutics, Inc. Antimicrobial compounds and methods of making and using the same
KR20160070066A (en) 2013-09-09 2016-06-17 멜린타 테라퓨틱스, 인크. Antimicrobial compunds and methods of making and using the same
DK3043827T3 (en) 2013-09-13 2019-08-26 Ionis Pharmaceuticals Inc MODULATORS OF COMPLEMENT FACTOR B
KR20160062069A (en) 2013-10-11 2016-06-01 아이오니스 파마수티컬즈, 인코포레이티드 Compositions for modulating c9orf72 expression
US20170037409A1 (en) 2013-12-24 2017-02-09 Ionis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
WO2015108046A1 (en) 2014-01-15 2015-07-23 株式会社新日本科学 Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent
JPWO2015108048A1 (en) 2014-01-15 2017-03-23 株式会社新日本科学 Chiral nucleic acid adjuvant and antitumor agent having antitumor activity
US10144933B2 (en) 2014-01-15 2018-12-04 Shin Nippon Biomedical Laboratories, Ltd. Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator
RU2016133035A (en) 2014-01-16 2018-02-21 Уэйв Лайф Сайенсес Лтд. CHIRAL DESIGN
CN116970607A (en) 2014-03-19 2023-10-31 Ionis制药公司 Compositions for modulating ataxin 2 expression
US9856475B2 (en) 2014-03-25 2018-01-02 Arcturus Therapeutics, Inc. Formulations for treating amyloidosis
CN110846316B (en) 2014-03-25 2023-10-31 阿克丘勒斯治疗公司 UNA oligomers with reduced off-target effects in gene silencing
EP3122365B1 (en) 2014-03-25 2023-05-03 Arcturus Therapeutics, Inc. Transthyretin allele selective una oligomers for gene silencing
LT3126499T (en) 2014-04-01 2020-07-27 Biogen Ma Inc. Compositions for modulating sod-1 expression
ES2932304T3 (en) 2014-04-17 2023-01-17 Biogen Ma Inc Compositions and methods for modulation of SMN2 splicing in a subject
AU2015252841B2 (en) 2014-05-01 2020-03-19 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating growth hormone receptor expression
JP6637442B2 (en) 2014-05-01 2020-01-29 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Ionis Pharmaceuticals,Inc. Compositions and methods for modulating complement factor B expression
BR112016022855B1 (en) 2014-05-01 2022-08-02 Ionis Pharmaceuticals, Inc COMPOUNDS AND COMPOSITIONS TO MODULATE THE EXPRESSION OF PKK AND ITS USES
WO2015190922A1 (en) 2014-06-10 2015-12-17 Erasmus University Medical Center Rotterdam Antisense oligonucleotides useful in treatment of pompe disease
US10400243B2 (en) 2014-11-25 2019-09-03 Ionis Pharmaceuticals, Inc. Modulation of UBE3A-ATS expression
MX2017011010A (en) 2015-02-26 2017-10-20 Ionis Pharmaceuticals Inc Allele specific modulators of p23h rhodopsin.
WO2016141236A1 (en) 2015-03-03 2016-09-09 Ionis Pharmaceuticals, Inc. Compositions for modulating mecp2 expression
WO2016141145A1 (en) 2015-03-03 2016-09-09 Ionis Pharmaceuticals, Inc. Methods for modulating mecp2 expression
US10947237B2 (en) 2015-03-11 2021-03-16 BioVersys AG Antimicrobial compounds and methods of making and using the same
US10519447B2 (en) 2015-04-01 2019-12-31 Arcturus Therapeutics, Inc. Therapeutic UNA oligomers and uses thereof
BR112017015864A2 (en) 2015-04-03 2018-07-31 Ionis Pharmaceuticals, Inc. compounds and methods for modulating tmprss6 expression
SG11201708468YA (en) 2015-04-16 2017-11-29 Ionis Pharmaceuticals Inc Compositions for modulating c9orf72 expression
WO2017015671A1 (en) 2015-07-23 2017-01-26 Arcturus Therapeutics, Inc. Compositions for treating amyloidosis
LU92821B1 (en) 2015-09-09 2017-03-20 Mologen Ag Combination comprising immunostimulatory oligonucleotides
GB2542425A (en) 2015-09-21 2017-03-22 Mologen Ag Means for the treatment of HIV
PE20181085A1 (en) 2015-10-08 2018-07-05 Ionis Pharmaceuticals Inc COMPOSITIONS AND METHODS TO MODULATE THE EXPRESSION OF ANGIOTENSINOGEN
WO2017079291A1 (en) 2015-11-02 2017-05-11 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating c90rf72
BR112018003291A2 (en) 2015-11-06 2018-09-25 Ionis Pharmaceuticals, Inc. modulating apolipoprotein expression (a)
US10993995B2 (en) 2015-12-07 2021-05-04 Erasmus University Medical Center Rotterdam Enzymatic replacement therapy and antisense therapy for pompe disease
WO2017193016A1 (en) 2016-05-06 2017-11-09 Melinta Therapeutics, Inc. Antimicrobials and methods of making and using same
EP3484908A4 (en) 2016-07-15 2020-04-08 AM Chemicals Llc Non-nucleosidic solid supports and phosphoramidite building blocks for oligonucleotide synthesis
NL2017295B1 (en) 2016-08-05 2018-02-14 Univ Erasmus Med Ct Rotterdam Antisense oligomeric compound for Pompe disease
NL2017294B1 (en) 2016-08-05 2018-02-14 Univ Erasmus Med Ct Rotterdam Natural cryptic exon removal by pairs of antisense oligonucleotides.
JOP20190065A1 (en) 2016-09-29 2019-03-28 Ionis Pharmaceuticals Inc Compounds and methods for reducing tau expression
US11401519B2 (en) 2017-06-07 2022-08-02 University Of Massachusetts Anti-ADAM33 oligonucleotides and related methods
TWI809004B (en) 2017-11-09 2023-07-21 美商Ionis製藥公司 Compounds and methods for reducing snca expression
PE20201501A1 (en) 2018-01-12 2020-12-29 Bristol Myers Squibb Co ANTI-SENSE OLIGONUCLEOTIDES ACTING ON ALPHA-SINUCLEIN, AND USES OF THESE
MX2020011913A (en) 2018-05-09 2021-01-29 Ionis Pharmaceuticals Inc Compounds and methods for reducing fxi expression.
EP3806861A1 (en) 2018-06-18 2021-04-21 University of Rochester Methods of treating schizophrenia and other neuropsychiatric disorders
AU2019396450A1 (en) 2018-12-11 2021-06-24 University Of Rochester Methods of treating schizophrenia and other neuropsychiatric disorders
TW202035694A (en) 2018-12-14 2020-10-01 美商百健Ma公司 Compositions and methods for treating and preventing amyotrophic lateral sclerosis
MX2021010152A (en) 2019-02-27 2021-09-14 Ionis Pharmaceuticals Inc Modulators of malat1 expression.
MX2021011921A (en) 2019-03-29 2021-10-26 Mitsubishi Tanabe Pharma Corp Compound, method and pharmaceutical composition for dux4 expression adjustment.
RU2731381C1 (en) * 2019-04-26 2020-09-02 Федеральное государственное бюджетное учреждение науки институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова Российской академии наук (ИБХ РАН) Nucleoside derivatives of 1,3-diaza-2-oxophenoxazine as herpesvirus replication inhibitors
CN114072501A (en) 2019-05-06 2022-02-18 马萨诸塞大学 anti-C9 ORF72 oligonucleotides and related methods
WO2021142245A1 (en) 2020-01-10 2021-07-15 Translate Bio, Inc. Compounds, pharmaceutical compositions and methods for modulating expression of muc5b in lung cells and tissues
WO2021154705A1 (en) 2020-01-27 2021-08-05 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Rab13 and net1 antisense oligonucleotides to treat metastatic cancer
CA3201661A1 (en) 2020-11-18 2022-05-27 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating angiotensinogen expression
JP2023554346A (en) 2020-12-18 2023-12-27 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 Compounds and methods for modulating factor XII
KR20230172502A (en) 2021-03-31 2023-12-22 바이오젠 엠에이 인코포레이티드 Treatment of amyotrophic lateral sclerosis

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992002534A2 (en) * 1990-08-03 1992-02-20 Sterling Drug, Inc. Compounds and methods for inhibiting gene expression
WO1992003464A1 (en) * 1990-08-28 1992-03-05 Microprobe Corporation Solid support synthesis of 3'-tailed oligonucleotides via a linking molecule
WO1995025814A1 (en) * 1994-03-18 1995-09-28 Lynx Therapeutics, Inc. Oligonucleotide n3'→p5' phosphoramidates: synthesis and compounds; hybridization and nuclease resistance properties
WO1995026972A1 (en) * 1994-03-31 1995-10-12 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
WO1999024452A2 (en) * 1997-11-07 1999-05-20 Isis Pharmaceuticals, Inc. Pyrimidine derivatives for labeled binding partners
WO2001057188A2 (en) * 2000-02-03 2001-08-09 Hyseq, Inc. Novel nucleic acids and polypeptides
WO2003004602A2 (en) * 2001-07-03 2003-01-16 Isis Pharmaceuticals, Inc. Nuclease resistant chimeric oligonucleotides

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992002534A2 (en) * 1990-08-03 1992-02-20 Sterling Drug, Inc. Compounds and methods for inhibiting gene expression
WO1992003464A1 (en) * 1990-08-28 1992-03-05 Microprobe Corporation Solid support synthesis of 3'-tailed oligonucleotides via a linking molecule
WO1995025814A1 (en) * 1994-03-18 1995-09-28 Lynx Therapeutics, Inc. Oligonucleotide n3'→p5' phosphoramidates: synthesis and compounds; hybridization and nuclease resistance properties
WO1995026972A1 (en) * 1994-03-31 1995-10-12 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
WO1999024452A2 (en) * 1997-11-07 1999-05-20 Isis Pharmaceuticals, Inc. Pyrimidine derivatives for labeled binding partners
WO2001057188A2 (en) * 2000-02-03 2001-08-09 Hyseq, Inc. Novel nucleic acids and polypeptides
WO2003004602A2 (en) * 2001-07-03 2003-01-16 Isis Pharmaceuticals, Inc. Nuclease resistant chimeric oligonucleotides

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
BARAWKAR ET AL: "Synthesis, biophysical properties, and nuclease resistance properties of mixed backbone oligodeoxynucleotides containing cationic internucleoside guanidinium linkages: Deoxynucleic guanidine/DNA chimeras", PNAS, vol. 95, September 1998 (1998-09-01), pages 11047 - 11052, XP002979594 *
CAULFIELD ET AL: "Achiral internucleoside linkages: CH2-CH2-NH and nH-CH2-CH2 linkages", BIOORGANIC AND MEDICINAL CHEMISTRY LETTERS, vol. 3, no. 12, March 1993 (1993-03-01), pages 2771 - 2776, XP002979595 *
HIRAO ET AL: "Most compact hairpin-turn structure exerted by a short DNA fragment, d(GCGAAGC) in solution: and extraordinarily stable structure resistant to nucleases and heat", NUCLEIC ACIDS RESEARCH, vol. 22, no. 4, January 1994 (1994-01-01), pages 576 - 582, XP002980322 *
KARPEISKI ET AL: "Substrate specificity of nuclease S1 from aspergilus oryzae in hydrolysis of low molecular weight substrates", BIOORGANICHESKAYA KHIMIYA, vol. 8, no. 3, January 1982 (1982-01-01), pages 386 - 395, XP001199634 *
KUZNETSOVA ET AL: "Hybridization properties and nuclease resistance of oligo(2'-O-tetrahydropyranylribonucleotides)", RUSSIAN J. OF BIOORGANIC CHEMISTRY, vol. 26, no. 1, January 2000 (2000-01-01), pages 69 - 70, XP008035031 *
PEYROTTES ET AL: "Synthesis, base paiing properties and nuclease resistance of oligothymidylate analogs containing methoxyphosphoramidate internucleoside linkages", NUCLEOTIDES AND NUCLEOTIDES, vol. 13, no. 10, January 1994 (1994-01-01), pages 2135 - 2149, XP002980323 *
QUARTIN ET AL: "Number and distribution of methylphosphonate linkages in oligodeoxynucleotides affect exo- and endonuclease sensitivity and ability to form RNase H substrates", NUCLEIC ACIDS RESEARCH, vol. 17, no. 18, November 1989 (1989-11-01), pages 7253 - 7262, XP000574936 *
SUN ET AL: "Triple-Helix Formation by alpha Oligodeoxynucleotides and alpha Oligodeoxynucleotide-Intercalator Conjugates", PROC NATL ACAD OF SCI, vol. 88, July 1991 (1991-07-01), pages 6023 - 6027, XP002979596 *
YOSHIZAWA ET AL: "Nuclease resistance of an extraordinarily thermostable mini-hairpin DNA fragment, d(GCGAAGC) and its application to in vitro protein synthesis", NUCLEIC ACIDS RESEARCH, vol. 22, no. 12, January 1994 (1994-01-01), pages 2217 - 2221, XP001084025 *
ZHAO ET AL: "Synthesis and Preliminary Biochemical Studies with 5'-Deoxy-5'-methylidyne Phosphonate Linked Thymidine Oligonucleotides", TETRAHEDRON LETTERS, vol. 37, no. 35, July 1996 (1996-07-01), pages 6239 - 6242, XP004030659 *

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9150606B2 (en) 2002-11-05 2015-10-06 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2'-modified nucleosides for use in gene modulation
US9598693B2 (en) 2006-01-27 2017-03-21 Ionis Pharmaceuticals, Inc. Oligomeric compounds and compositions for the use in modulation of micrornas
US8846639B2 (en) 2008-04-04 2014-09-30 Isis Pharmaceutical, Inc. Oligomeric compounds comprising bicyclic nucleosides and having reduced toxicity
US9399774B2 (en) 2010-04-29 2016-07-26 Ionis Pharmaceuticals, Inc. Modulation of transthyretin expression
US9175291B2 (en) 2012-10-11 2015-11-03 Isis Pharmaceuticals Inc. Modulation of androgen receptor expression
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