[go: up one dir, main page]

PE20220013A1 - Oligonucleotidos para modular la expresion de tau - Google Patents

Oligonucleotidos para modular la expresion de tau

Info

Publication number
PE20220013A1
PE20220013A1 PE2021000777A PE2021000777A PE20220013A1 PE 20220013 A1 PE20220013 A1 PE 20220013A1 PE 2021000777 A PE2021000777 A PE 2021000777A PE 2021000777 A PE2021000777 A PE 2021000777A PE 20220013 A1 PE20220013 A1 PE 20220013A1
Authority
PE
Peru
Prior art keywords
oligonucleotide
expression
tau
oligonucleotides
modulate
Prior art date
Application number
PE2021000777A
Other languages
English (en)
Inventor
Peter Hagedorn
Anja Mølhart Høg
Richard E Olson
Marianne L Jensen
Original Assignee
Hoffmann La Roche
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 Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of PE20220013A1 publication Critical patent/PE20220013A1/es

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y301/00—Hydrolases acting on ester bonds (3.1)
    • C12Y301/26—Endoribonucleases producing 5'-phosphomonoesters (3.1.26)
    • C12Y301/26004—Ribonuclease H (3.1.26.4)
    • 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
    • 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
    • C12N2310/322—2'-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 ===---===
    • 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
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
    • 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
    • C12N2310/351—Conjugate
    • 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
    • C12N2320/00—Applications; Uses
    • C12N2320/50—Methods for regulating/modulating their activity
    • C12N2320/51—Methods for regulating/modulating their activity modulating the chemical stability, e.g. nuclease-resistance
    • 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
    • C12N2330/00—Production
    • C12N2330/30—Production chemically synthesised

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Immunology (AREA)
  • Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La presente invencion se refiere a un oligonucleotido antisentido que reduce la expresion de Tau en una celula diana. Se refiere ademas a un conjugado del oligonucleotido y composicion farmaceutica y metodo in vivo o in vitro para modular la expresion de Tau. El oligonucleotido es util en el tratamiento de taupatias, enfermedad de Alzheimer, demencia frontotemporal (FTD), FTDP-17, paralisis supranuclear progresiva (PSP), encefalopatia traumatica cronica (CTE), degeneracion ganglionar corticobasal (CBD), epilepsia, sindrome de Dravet, depresion, trastornos convulsivos y trastornos motores
PE2021000777A 2018-07-03 2019-07-03 Oligonucleotidos para modular la expresion de tau PE20220013A1 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862693851P 2018-07-03 2018-07-03
US201862726005P 2018-08-31 2018-08-31
PCT/EP2019/067799 WO2020007892A1 (en) 2018-07-03 2019-07-03 Oligonucleotides for modulating tau expression

Publications (1)

Publication Number Publication Date
PE20220013A1 true PE20220013A1 (es) 2022-01-11

Family

ID=67439176

Family Applications (2)

Application Number Title Priority Date Filing Date
PE2020001998A PE20210346A1 (es) 2018-07-03 2019-07-03 Oligonucleotidos para modular la expresion de tau
PE2021000777A PE20220013A1 (es) 2018-07-03 2019-07-03 Oligonucleotidos para modular la expresion de tau

Family Applications Before (1)

Application Number Title Priority Date Filing Date
PE2020001998A PE20210346A1 (es) 2018-07-03 2019-07-03 Oligonucleotidos para modular la expresion de tau

Country Status (19)

Country Link
US (5) US11279929B2 (es)
EP (1) EP3818159A1 (es)
JP (3) JP7102557B2 (es)
KR (3) KR102723469B1 (es)
CN (2) CN120137967A (es)
AU (2) AU2019297391B2 (es)
BR (1) BR112020026973A2 (es)
CA (2) CA3247235A1 (es)
CL (6) CL2020003457A1 (es)
CR (3) CR20210058A (es)
IL (1) IL279056A (es)
MX (3) MX2020013366A (es)
MY (1) MY206038A (es)
PE (2) PE20210346A1 (es)
PH (1) PH12020552276A1 (es)
RU (1) RU2768285C1 (es)
SG (1) SG11202012759XA (es)
TW (2) TW202519658A (es)
WO (1) WO2020007892A1 (es)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013148260A1 (en) 2012-03-30 2013-10-03 Washington University Methods for modulating tau expression for reducing seizure and modifying a neurodegenerative syndrome
CN106332323B (zh) * 2012-08-21 2020-02-14 特电株式会社 流体加热装置
TW202246503A (zh) 2013-07-19 2022-12-01 美商百健Ｍａ公司 用於調節τ蛋白表現之組合物
AU2019218987B2 (en) 2018-02-12 2025-04-24 Ionis Pharmaceuticals, Inc. Modified compounds and uses thereof
MY206038A (en) 2018-07-03 2024-11-26 Hoffmann La Roche Oligonucleotides for modulating tau expression
CN115210377A (zh) * 2020-03-01 2022-10-18 波涛生命科学有限公司 寡核苷酸组合物及其方法
AU2021246024A1 (en) * 2020-03-30 2022-10-27 Alnylam Pharmaceuticals, Inc. Microtubule associated protein Tau (MAPT) iRNA agent compositions and methods of use thereof
CA3227412A1 (en) * 2021-07-23 2023-01-26 Biogen Ma Inc. Methods for reducing tau expression
WO2025188990A1 (en) * 2024-03-08 2025-09-12 Eli Lilly And Company Mapt antisense oligonucleotide

Family Cites Families (92)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4711955A (en) 1981-04-17 1987-12-08 Yale University Modified nucleotides and methods of preparing and using same
CA1223831A (en) 1982-06-23 1987-07-07 Dean Engelhardt Modified nucleotides, methods of preparing and utilizing and compositions containing the same
ATE239484T1 (de) 1991-10-24 2003-05-15 Isis Pharmaceuticals Inc Derivatisierte oligonukleotide mit verbessertem aufnahmevermögen
US5792608A (en) 1991-12-12 1998-08-11 Gilead Sciences, Inc. Nuclease stable and binding competent oligomers and methods for their use
NL9201440A (nl) 1992-08-11 1994-03-01 Univ Leiden Triantennaire clusterglycosiden, hun bereiding en toepassing.
US5525711A (en) 1994-05-18 1996-06-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Pteridine nucleotide analogs as fluorescent DNA probes
JP3756313B2 (ja) 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
KR100414936B1 (ko) 1997-09-12 2004-01-13 엑시콘 에이/에스 이환 및 삼환 뉴클레오시드, 뉴클레오타이드 및올리고뉴클레오타이드 동족체
NZ513402A (en) 1999-02-12 2003-06-30 Sankyo Co Novel nucleosides and oligonucleotide analogues
PT1178999E (pt) 1999-05-04 2007-06-26 Santaris Pharma As Análogos de l-ribo-lna
US6617442B1 (en) 1999-09-30 2003-09-09 Isis Pharmaceuticals, Inc. Human Rnase H1 and oligonucleotide compositions thereof
WO2003022987A2 (en) 2001-07-26 2003-03-20 Eos Biotechnology, Inc. Methods of diagnosis of hepatitis c infection, compositions and methods of screening for modulators of hepatitis c infection
DK2284266T3 (da) 2002-11-14 2014-01-13 Thermo Fisher Scient Biosciences Inc sIRNA-MOLEKYLE MOD TP53
DK2752488T3 (da) 2002-11-18 2020-04-20 Roche Innovation Ct Copenhagen As Antisense-design
US7250289B2 (en) * 2002-11-20 2007-07-31 Affymetrix, Inc. Methods of genetic analysis of mouse
US20060257851A1 (en) 2002-11-26 2006-11-16 Itzhak Bentwich Bioinformatically detectable group of novel viral regulatory genes and uses thereof
BRPI0411219A (pt) 2003-06-12 2006-07-18 Nucleonics Inc seqüências de hbv e hcv conservadas úteis para silenciamento de gene
US20050244851A1 (en) 2004-01-13 2005-11-03 Affymetrix, Inc. Methods of analysis of alternative splicing in human
US7374927B2 (en) 2004-05-03 2008-05-20 Affymetrix, Inc. Methods of analysis of degraded nucleic acid samples
AU2005248147A1 (en) 2004-05-11 2005-12-08 Alphagen Co., Ltd. Polynucleotides for causing RNA interference and method for inhibiting gene expression using the same
US20080125583A1 (en) 2005-02-11 2008-05-29 International Business Machines Corporation Ribonucleic acid interference molecules
WO2007031091A2 (en) 2005-09-15 2007-03-22 Santaris Pharma A/S Rna antagonist compounds for the modulation of p21 ras expression
ES2516815T3 (es) 2006-01-27 2014-10-31 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos modificados en la posición 6
WO2007106407A2 (en) 2006-03-10 2007-09-20 Wyeth Microarray for monitoring gene expression in multiple strains of streptococcus pneumoniae
WO2007136989A2 (en) 2006-05-05 2007-11-29 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of dgat2
US7666854B2 (en) 2006-05-11 2010-02-23 Isis Pharmaceuticals, Inc. Bis-modified bicyclic nucleic acid analogs
CA2651453C (en) 2006-05-11 2014-10-14 Isis Pharmaceuticals, Inc. 5'-modified bicyclic nucleic acid analogs
JP5665317B2 (ja) 2006-10-18 2015-02-04 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 アンチセンス化合物
DK2149605T3 (da) 2007-03-22 2013-09-30 Santaris Pharma As Korte RNA antagonist forbindelser til modulering af det ønskede mRNA
WO2008150729A2 (en) 2007-05-30 2008-12-11 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
AU2008272918B2 (en) 2007-07-05 2012-09-13 Isis Pharmaceuticals, Inc. 6-disubstituted bicyclic nucleic acid analogs
US8546556B2 (en) 2007-11-21 2013-10-01 Isis Pharmaceuticals, Inc Carbocyclic alpha-L-bicyclic nucleic acid analogs
WO2009090182A1 (en) 2008-01-14 2009-07-23 Santaris Pharma A/S C4'-substituted - dna nucleotide gapmer oligonucleotides
EP2285819B1 (en) 2008-04-04 2013-10-16 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising neutrally linked terminal bicyclic nucleosides
EP2310021A4 (en) 2008-07-10 2012-06-27 Merck Sharp & Dohme METHOD OF USE OF COMPOSITIONS WITH MIR-192 AND / OR MIR-215 FOR THE TREATMENT OF CANCER
WO2010036698A1 (en) 2008-09-24 2010-04-01 Isis Pharmaceuticals, Inc. Substituted alpha-l-bicyclic nucleosides
EP2177615A1 (en) 2008-10-10 2010-04-21 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Method for a genome wide identification of expression regulatory sequences and use of genes and molecules derived thereof for the diagnosis and therapy of metabolic and/or tumorous diseases
CN105907756A (zh) 2008-12-18 2016-08-31 戴瑟纳制药公司 延长的dicer酶底物和特异性抑制基因表达的方法
WO2010093788A2 (en) 2009-02-11 2010-08-19 Dicerna Pharmaceuticals, Inc. Multiplex dicer substrate rna interference molecules having joining sequences
US8609097B2 (en) 2009-06-10 2013-12-17 Hoffmann-La Roche Inc. Use of an anti-Tau pS422 antibody for the treatment of brain diseases
US9012421B2 (en) 2009-08-06 2015-04-21 Isis Pharmaceuticals, Inc. Bicyclic cyclohexose nucleic acid analogs
US8846637B2 (en) 2010-06-08 2014-09-30 Isis Pharmaceuticals, Inc. Substituted 2′-amino and 2′-thio-bicyclic nucleosides and oligomeric compounds prepared therefrom
EP3587574B1 (en) 2010-08-17 2022-03-16 Sirna Therapeutics, Inc. Rna interference mediated inhibition of hepatitis b virus (hbv) gene expression using short interfering nucleic acid (sina)
WO2012054723A2 (en) 2010-10-22 2012-04-26 Opko Curna Llc Treatment of alpha-l-iduronidase (idua) related diseases by inhibition of natural antisense transcript to idua
RS58982B1 (sr) 2010-10-28 2019-08-30 Benitec Biopharma Ltd Lečenje hbv
EP2673361B1 (en) 2011-02-08 2016-04-13 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
BR112013026306A2 (pt) 2011-04-20 2017-09-05 Roche Glycart Ag MÉTODO E CONSTRUTOS PARA A PASSAGEM DE PENDENTE DO pH DA BARREIRA SANGUE-CÉREBRO
JP6042871B2 (ja) 2011-04-21 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． Ｂ型肝炎ウイルス（ｈｂｖ）発現の調節
CN106434665B (zh) 2011-06-30 2021-06-08 箭头药业股份有限公司 用于抑制乙型肝炎病毒的基因表达的组合物和方法
WO2013022967A1 (en) 2011-08-11 2013-02-14 Isis Pharmaceuticals, Inc. Gapped oligomeric compounds comprising 5'-modified deoxyribonucleosides in the gap and uses thereof
CN104136451A (zh) 2011-09-07 2014-11-05 玛瑞纳生物技术有限公司 具有构象限制的单体的核酸化合物的合成和用途
SMT201800109T1 (it) 2011-09-19 2018-05-02 Axon Neuroscience Se Terapia a base di proteine e diagnosi di una patologia mediata da tau nella malattia di alzheimer
WO2013148260A1 (en) 2012-03-30 2013-10-03 Washington University Methods for modulating tau expression for reducing seizure and modifying a neurodegenerative syndrome
US9221864B2 (en) 2012-04-09 2015-12-29 Isis Pharmaceuticals, Inc. Tricyclic nucleic acid analogs
WO2013159109A1 (en) 2012-04-20 2013-10-24 Isis Pharmaceuticals, Inc. Modulation of hepatitis b virus (hbv) expression
WO2013166264A2 (en) 2012-05-02 2013-11-07 University Of Georgia Research Foundation, Inc. Methods for altering virus replication
CN104582737A (zh) * 2012-05-16 2015-04-29 Rana医疗有限公司 用于调节apoa1和abca1表达的组合物和方法
CN104661664B (zh) 2012-07-13 2020-07-03 波涛生命科学有限公司 手性控制
CA2882966A1 (en) 2012-08-31 2014-03-06 Aptamir Therapeutics, Inc. Mirna modulators of chronic visceral inflammation
SG11201503821YA (en) 2012-11-15 2015-06-29 Roche Innovation Ct Copenhagen As Oligonucleotide conjugates
ES2807379T3 (es) 2013-03-14 2021-02-22 Ionis Pharmaceuticals Inc Composiciones y métodos para regular la expresión de Tau
KR102482890B1 (ko) 2013-05-01 2022-12-30 아이오니스 파마수티컬즈, 인코포레이티드 아포지질단백질 (a) 발현을 조절하는 조성물 및 방법
DK3013959T3 (da) 2013-06-27 2020-02-17 Roche Innovation Ct Copenhagen As Antisense-oligomerer og konjugater målrettet pcsk9
EP3730614A3 (en) * 2013-07-02 2020-12-30 Ionis Pharmaceuticals, Inc. Modulators of growth hormone receptor
TW202246503A (zh) * 2013-07-19 2022-12-01 美商百健Ｍａ公司 用於調節τ蛋白表現之組合物
US20160319361A1 (en) 2013-08-28 2016-11-03 Caris Life Sciences Switzerland Holdings Gmbh Oligonucleotide probes and uses thereof
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
SG11201605970QA (en) 2014-01-30 2016-08-30 Hoffmann La Roche Novel dihydroquinolizinones for the treatment and prophylaxis of hepatitis b virus infection
WO2015173164A1 (en) 2014-05-13 2015-11-19 F. Hoffmann-La Roche Ag Novel dihydroquinolizinones for the treatment and prophylaxis of hepatitis b virus infection
GB201408623D0 (en) 2014-05-15 2014-07-02 Santaris Pharma As Oligomers and oligomer conjugates
US20170211064A1 (en) * 2014-07-29 2017-07-27 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating tau expression
KR20170068469A (ko) 2014-10-10 2017-06-19 에프. 호프만-라 로슈 아게 ＧａｌＮＡｃ 포스포라미다이트, 그의 핵산 컨쥬게이트 및 그의 용도
JP2017536119A (ja) 2014-11-19 2017-12-07 ロシュ イノベーション センター コペンハーゲン エーエス キラルホスホロチオエート連結を含むｌｎａギャップマーオリゴヌクレオチド
EP3253871A1 (en) 2015-02-04 2017-12-13 Bristol-Myers Squibb Company Lna oligonucleotides with alternating flanks
PE20171766A1 (es) * 2015-02-04 2017-12-21 Hoffmann La Roche Oligomeros antisentido de tau y usos de estos
EP3256471B1 (en) 2015-02-11 2018-12-12 F. Hoffmann-La Roche AG Novel 2-oxo-6,7-dihydrobenzo[a]quinolizine-3-carboxylic acid derivatives for the treatment and prophylaxis of hepatitis b virus infection
WO2016151523A1 (en) 2015-03-25 2016-09-29 Università Degli Studi Di Trento Rna interference mediated therapy for neurodegenerative diseases
WO2016177655A1 (en) 2015-05-04 2016-11-10 F. Hoffmann-La Roche Ag Tetrahydropyridopyrimidines and tetrahydropyridopyridines as inhibitors of hbsag (hbv surface antigen) and hbv dna production for the treatment of hepatitis b virus infections
WO2017009679A1 (en) 2015-07-13 2017-01-19 Otis Elevator Company Deterrent device inhibition key
AU2016296592B2 (en) 2015-07-17 2021-08-19 Arcturus Therapeutics, Inc. Compositions and agents against Hepatitis B virus and uses thereof
KR20180038465A (ko) 2015-08-07 2018-04-16 애로우헤드 파마슈티컬스 인코포레이티드 Ｂ형 간염 바이러스 감염에 대한 ｒｎａｉ 치료법
WO2017066712A2 (en) 2015-10-16 2017-04-20 The Children's Medical Center Corporation Modulators of telomere disease
EP3390634A4 (en) * 2015-12-14 2019-08-14 Cold Spring Harbor Laboratory COMPOSITIONS AND METHODS FOR THE TREATMENT OF EYE DISEASES
JOP20200228A1 (ar) 2015-12-21 2017-06-16 Novartis Ag تركيبات وطرق لخفض تعبير البروتين tau
EP3442983A1 (en) 2016-04-14 2019-02-20 H. Hoffnabb-La Roche Ag TRITYL-MONO-Ga1NAc COMPOUNDS AND THEIR USE
MA45496A (fr) 2016-06-17 2019-04-24 Hoffmann La Roche Molécules d'acide nucléique pour la réduction de l'arnm de padd5 ou pad7 pour le traitement d'une infection par l'hépatite b
JOP20190065A1 (ar) * 2016-09-29 2019-03-28 Ionis Pharmaceuticals Inc مركبات وطرق لتقليل التعبير عن tau
WO2018059718A1 (en) 2016-09-30 2018-04-05 Rijk Zwaan Zaadteelt En Zaadhandel B.V. Peronospora resistance in spinacia oleracea
AU2018350693B2 (en) 2017-10-16 2021-03-04 F. Hoffmann-La Roche Ag Nucleic acid molecule for reduction of PAPD5 and PAPD7 mRNA for treating hepatitis B infection
BR112020013431A2 (pt) 2018-01-29 2020-12-01 F. Hoffmann-La Roche Ag processo para a preparação de conjugados de galnac-oligonucleotídeo
MY206038A (en) 2018-07-03 2024-11-26 Hoffmann La Roche Oligonucleotides for modulating tau expression

Also Published As

Publication number Publication date
CN112567033A (zh) 2021-03-26
CL2024001778A1 (es) 2024-09-27
JP7102557B2 (ja) 2022-07-19
CR20210178A (es) 2021-05-11
AU2019297391B2 (en) 2023-01-12
PE20210346A1 (es) 2021-02-25
AU2023202255B2 (en) 2025-07-10
MX2025000060A (es) 2025-02-10
CL2021001071A1 (es) 2021-10-15
EP3818159A1 (en) 2021-05-12
NZ770352A (en) 2024-07-05
US20220177884A1 (en) 2022-06-09
JP7604423B2 (ja) 2024-12-23
US11279929B2 (en) 2022-03-22
MX2020013366A (es) 2021-03-09
SG11202012759XA (en) 2021-01-28
US20210123054A1 (en) 2021-04-29
MY206038A (en) 2024-11-26
BR112020026973A2 (pt) 2021-04-06
US11753640B2 (en) 2023-09-12
CR20210058A (es) 2021-03-22
JP2025029212A (ja) 2025-03-05
AU2019297391A1 (en) 2020-12-24
CL2024003932A1 (es) 2025-04-21
KR102723469B1 (ko) 2024-10-31
TW202020151A (zh) 2020-06-01
KR20240157136A (ko) 2024-10-31
US12163131B2 (en) 2024-12-10
CL2020003457A1 (es) 2021-06-04
CL2024001779A1 (es) 2024-10-25
WO2020007892A1 (en) 2020-01-09
CA3247235A1 (en) 2025-11-29
MX2025000063A (es) 2025-02-10
RU2768285C1 (ru) 2022-03-23
CL2021001072A1 (es) 2021-10-15
JP2021529525A (ja) 2021-11-04
TWI862501B (zh) 2024-11-21
JP2022141739A (ja) 2022-09-29
IL279056A (en) 2021-01-31
CN120137967A (zh) 2025-06-13
TW202519658A (zh) 2025-05-16
KR20210028235A (ko) 2021-03-11
PH12020552276A1 (en) 2021-07-12
AU2023202255A1 (en) 2023-05-11
CR20210179A (es) 2022-05-23
KR20230143199A (ko) 2023-10-11
KR102585973B1 (ko) 2023-10-10
US20200010831A1 (en) 2020-01-09
CA3103054A1 (en) 2020-01-09
US20240026360A1 (en) 2024-01-25
US20250051777A1 (en) 2025-02-13

Similar Documents

Publication Publication Date Title
PE20220013A1 (es) Oligonucleotidos para modular la expresion de tau
BR112022010349A2 (pt) Compostos bifuncionais para degradar btk por meio de via da ubiquitina-proteossoma
CY1125025T1 (el) 2-φορμυλ-3-υδροξυφαινυλοξυμεθυλ ενωσεις ικανες ρυθμισης αιμοσφαιρινης
CL2008002744A1 (es) Compuestos derivados de 1,3-disustituidos-4-fenil-1h-piridin-2-ona, moduladores alostericos del receptor glutamatérgico mglur2; composición farmacéutica y uso de los compuestos en el tratamiento de afecciones neurológicas y siquiatricas mediadas por mglur2.
PH12022550359A1 (en) Nonpeptide somatostatin type 5 receptor agonists and uses thereof
MX392668B (es) Composiciones nasales de cannabidiol
CL2016001595A1 (es) Moduladores de tetrahidropiridopirazinas de gpr6.
EA201001371A1 (ru) Конденсированные пиримидиноновые соединения как модуляторы trpv3
CR20110103A (es) Heteroarilos sustituidos
MX2019000588A (es) Moduladores de la somatostatina y usos de los mismos.
CL2021003257A1 (es) Pirazolo-piridinas heteroaromáticas sustituidas y su uso como moduladores del receptor glun2b.
CL2020001495A1 (es) Composiciones y método para el tratamiento de enfermedades metabólicas
CY1118966T1 (el) Νεες συνθεσεις για την προληψη και/ή την θεραπεια εκφυλιστικων διαταραχων του κεντρικου νευρικου συστηματος
CL2012001031A1 (es) Compuestos derivados de 2-oxo-1-pirrolidinil-imidazotiadiazol; composición farmacéutica que los comprende; útiles para el tratamiento de la epilepsia, transtornos neurológicos, entre otros.
MX2020007586A (es) Proceso de fabricacion de moduladores de somatostatina.
WO2020132378A3 (en) Compositions and methods of treatment for neurological disorders comprising depression
CR20220656A (es) Unión de anticuerpos multiespecíficos a bcma
EA201991898A1 (ru) Двойные ингибиторы magl и faah
MX383582B (es) Sulfonamidas como agonistas de gpr40 y gpr120.
MX2010005704A (es) Derivados de cromano como modulares del trpv3.
CL2020002038A1 (es) Oligonucleótidos para modular la expresión de tmem106b.
MX2020005952A (es) Uso de mir101 o mir128 en el tratamiento de trastornos convulsivos.
UA104861C2 (uk) Похідні хроману як модулятори trpv3
CL2008003895A1 (es) Compuestos derivados de 5-o-sustituido 3-n-fenil-1,3,4-oxadiazolonas, composicion farmaceutica, proceso de preparacion, y su uso para el tratamiento de un trastorno influenciado positivamente por la inhibicion de faah tal como trastornos alimenticios y patologias neurologicas y psiquiatricas, entre otras.
AR121945A2 (es) Oligonucleótidos para modular la expresión de tau