ZA201801600B - Compounds and methods for modulating angiotensinogen expression - Google Patents

Compounds and methods for modulating angiotensinogen expression

Info

Publication number
ZA201801600B
ZA201801600B ZA2018/01600A ZA201801600A ZA201801600B ZA 201801600 B ZA201801600 B ZA 201801600B ZA 2018/01600 A ZA2018/01600 A ZA 2018/01600A ZA 201801600 A ZA201801600 A ZA 201801600A ZA 201801600 B ZA201801600 B ZA 201801600B
Authority
ZA
South Africa
Prior art keywords
modulating
compounds
methods
angiotensinogen expression
angiotensinogen
Prior art date
Application number
ZA2018/01600A
Other languages
English (en)
Inventor
Adam Mullick
Mark J Graham
Punit P Seth
Susan M Freier
Original Assignee
Ionis Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ionis Pharmaceuticals Inc filed Critical Ionis Pharmaceuticals Inc
Publication of ZA201801600B publication Critical patent/ZA201801600B/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088Compounds having three or more nucleosides or nucleotides
    • A61K31/712Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088Compounds having three or more nucleosides or nucleotides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • 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
    • 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
    • C07H21/02Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
    • 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
    • C07H21/04Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-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
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-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
    • C12N15/1136Non-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 against growth factors, growth regulators, cytokines, lymphokines or hormones
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/11Antisense
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/14Type of nucleic acid interfering nucleic acids [NA]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/31Chemical structure of the backbone
    • C12N2310/315Phosphorothioates
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/31Chemical structure of the backbone
    • C12N2310/316Phosphonothioates
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/32Chemical structure of the sugar
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/33Chemical structure of the base
    • C12N2310/334Modified C
    • C12N2310/33415-Methylcytosine
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/35Nature of the modification
    • C12N2310/351Conjugate

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cardiology (AREA)
  • Endocrinology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)
  • Peptides Or Proteins (AREA)
ZA2018/01600A 2015-10-08 2018-03-08 Compounds and methods for modulating angiotensinogen expression ZA201801600B (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562238831P 2015-10-08 2015-10-08
PCT/US2016/056068 WO2017062816A2 (en) 2015-10-08 2016-10-07 Compounds and methods for modulating angiotensinogen expression

Publications (1)

Publication Number Publication Date
ZA201801600B true ZA201801600B (en) 2019-01-30

Family

ID=58488579

Family Applications (1)

Application Number Title Priority Date Filing Date
ZA2018/01600A ZA201801600B (en) 2015-10-08 2018-03-08 Compounds and methods for modulating angiotensinogen expression

Country Status (18)

Country Link
US (2) US10912792B2 (https=)
EP (3) EP3960183A1 (https=)
JP (4) JP2018530325A (https=)
KR (2) KR20180055898A (https=)
CN (2) CN113817735A (https=)
AU (3) AU2016334114B2 (https=)
BR (2) BR122020023854B1 (https=)
CA (1) CA2998898A1 (https=)
CL (2) CL2018000899A1 (https=)
CO (1) CO2018002598A2 (https=)
HK (1) HK1258275A1 (https=)
IL (2) IL295971A (https=)
MX (2) MX392014B (https=)
MY (1) MY200263A (https=)
PE (1) PE20181085A1 (https=)
SG (1) SG10202003148VA (https=)
WO (1) WO2017062816A2 (https=)
ZA (1) ZA201801600B (https=)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3215908A1 (en) 2014-05-22 2015-11-26 Alnylam Pharmaceuticals, Inc. Angiotensinogen (agt) irna compositions and methods of use thereof
TWI851574B (zh) * 2018-05-14 2024-08-11 美商阿尼拉製藥公司 血管收縮素原(AGT)iRNA組成物及其使用方法
WO2020236755A2 (en) * 2019-05-17 2020-11-26 Ionis Pharmaceuticals, Inc. Angiotensin ii type 1 receptor targeted oligonucleotides and uses thereof
KR20220115946A (ko) * 2019-11-13 2022-08-19 알닐람 파마슈티칼스 인코포레이티드 안지오텐시노겐 (agt) 관련 장애를 치료하기 위한 방법 및 조성물
US11649458B2 (en) * 2020-05-05 2023-05-16 University Of Kentucky Research Foundation Inhibiting angiotensinogen to attenuate aortic pathology in Marfan syndrome
EP4136092B1 (en) 2020-11-18 2024-07-31 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating angiotensinogen expression
CN114763547A (zh) * 2021-01-14 2022-07-19 施能康生物科技有限公司 靶向血管紧张素原的核酸及其用途
WO2022232650A1 (en) * 2021-04-30 2022-11-03 Ionis Pharmaceuticals, Inc. Methods for reducing agt expression
US20240401045A1 (en) * 2021-10-01 2024-12-05 Adarx Pharmaceuticals, Inc. Angiotensinogen-modulating compositions and methods of use thereof
CN120775847A (zh) * 2021-10-20 2025-10-14 厦门甘宝利生物医药有限公司 Agt抑制剂及其用途
IL312811A (en) * 2021-11-16 2024-07-01 Shanghai Argo Biopharmaceutical Co Ltd Composition and method for inhibiting angiotensinogen (agt) protein expression
US20250197853A1 (en) * 2021-11-19 2025-06-19 Tuojie Biotech (Shanghai) Co., Ltd. Sirna targeting angiotensinogen and pharmaceutical use of sirna
WO2023138650A1 (zh) * 2022-01-20 2023-07-27 上海拓界生物医药科技有限公司 一种dsRNA、其应用及制备方法
CN117264948B (zh) * 2022-06-14 2024-05-10 广州必贝特医药股份有限公司 抑制血管紧张素原基因表达的RNAi抑制剂及其应用
WO2024013334A1 (en) * 2022-07-15 2024-01-18 Silence Therapeutics Gmbh Nucleic acids for inhibiting expression of agt in a cell
WO2024031008A2 (en) * 2022-08-03 2024-02-08 Sirnaomics, Inc. Combination sirna and peptide docking vehicle (pdov) compositions and methods of their use for improved regulation and functionality
CN120303402A (zh) * 2022-09-16 2025-07-11 圣诺制药公司 产品与组合物
CN120981570A (zh) * 2022-12-20 2025-11-18 靖因药业有限公司 靶向agt的多核酸分子及其用途
CN120752336A (zh) * 2022-12-22 2025-10-03 圣诺制药公司 产品和组合物
CN119530218A (zh) * 2023-08-30 2025-02-28 苏州炫景生物科技有限公司 双链寡核苷酸及其在抑制血管紧张素原表达中的应用
WO2024234831A1 (zh) * 2023-05-15 2024-11-21 苏州时安生物技术有限公司 一种用于调节血管紧张素原基因表达的双链rna、其缀合物、药物组合物及用途
EP4562158A1 (en) 2023-06-13 2025-06-04 Arnatar Therapeutics, Inc Advanced rna targeting (arnatar) for angiotensinogen
WO2025097040A1 (en) * 2023-11-03 2025-05-08 Ionis Pharmaceuticals, Inc. Methods and compositions for reducing angiotensinogen
CN118995714B (zh) * 2024-09-26 2025-12-12 杭州天龙药业有限公司 靶向抑制AGT基因表达的siRNA及其在治疗高血压中的应用

Family Cites Families (81)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
FR2567892B1 (fr) 1984-07-19 1989-02-17 Centre Nat Rech Scient Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5506337A (en) 1985-03-15 1996-04-09 Antivirals Inc. Morpholino-subunit combinatorial library and method
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
ATE269870T1 (de) 1989-10-24 2004-07-15 Isis Pharmaceuticals Inc 2'-modifizierte oligonukleotide
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
GB9009980D0 (en) 1990-05-03 1990-06-27 Amersham Int Plc Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides
ES2116977T3 (es) 1990-05-11 1998-08-01 Microprobe Corp Soportes solidos para ensayos de hibridacion de acidos nucleicos y metodos para inmovilizar oligonucleotidos de modo covalente.
US6582908B2 (en) 1990-12-06 2003-06-24 Affymetrix, Inc. Oligonucleotides
EP0538194B1 (de) 1991-10-17 1997-06-04 Novartis AG Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
EP0577558A2 (de) 1992-07-01 1994-01-05 Ciba-Geigy Ag Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte
AU6449394A (en) 1993-03-30 1994-10-24 Sterling Winthrop Inc. Acyclic nucleoside analogs and oligonucleotide sequences containing them
US5801154A (en) 1993-10-18 1998-09-01 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of multidrug resistance-associated protein
US5446137B1 (en) 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
US5519134A (en) 1994-01-11 1996-05-21 Isis Pharmaceuticals, Inc. Pyrrolidine-containing monomers and oligomers
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
AU1039397A (en) 1995-11-22 1997-06-27 Johns Hopkins University, The Ligands to enhance cellular uptake of biomolecules
CA2248932A1 (en) 1996-03-15 1997-09-18 University Of Florida Oligonucleotides targeted to angiotensinogen mrna
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
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
AU9063398A (en) 1997-09-12 1999-04-05 Exiqon A/S Oligonucleotide analogues
US20030228597A1 (en) 1998-04-13 2003-12-11 Cowsert Lex M. Identification of genetic targets for modulation by oligonucleotides and generation of oligonucleotides for gene modulation
US6300319B1 (en) 1998-06-16 2001-10-09 Isis Pharmaceuticals, Inc. Targeted oligonucleotide conjugates
US6043352A (en) 1998-08-07 2000-03-28 Isis Pharmaceuticals, Inc. 2'-O-Dimethylaminoethyloxyethyl-modified oligonucleotides
DE60005159T2 (de) 1999-03-05 2004-07-22 G.D. Searle Llc, Chicago Kombinationstherapie von angiotensin-konvertierendem enzym hemmer und epoxy-steroidalem aldosteron antagonist zur behandlung von kardiovaskulären erkrankungen
WO2000063364A2 (en) 1999-04-21 2000-10-26 American Home Products Corporation Methods and compositions for inhibiting the function of polynucleotide sequences
EP1178999B1 (en) 1999-05-04 2007-03-14 Santaris Pharma A/S L-ribo-lna analogues
US6525191B1 (en) 1999-05-11 2003-02-25 Kanda S. Ramasamy Conformationally constrained L-nucleosides
US6902888B1 (en) 1999-05-21 2005-06-07 Myriad Genetics, Inc. Diabetes gene
AU5016200A (en) 1999-05-21 2000-12-12 Myriad Genetics, Inc. Diabetes gene
ES2261270T3 (es) 1999-12-30 2006-11-16 K.U. LEUVEN RESEARCH & DEVELOPMENT Acidos nucleicos que contienen ciclohexeno.
US7491805B2 (en) 2001-05-18 2009-02-17 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US6906182B2 (en) 2000-12-01 2005-06-14 Cell Works Therapeutics, Inc. Conjugates of glycosylated/galactosylated peptide, bifunctional linker, and nucleotidic monomers/polymers, and related compositions and method of use
JP2005504020A (ja) 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 ヌクレアーゼ耐性キメラオリゴヌクレオチド
CA2504694C (en) 2002-11-05 2013-10-01 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
US8604183B2 (en) 2002-11-05 2013-12-10 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2′-modified nucleosides for use in gene modulation
EP2305812A3 (en) 2002-11-14 2012-06-06 Dharmacon, Inc. Fuctional and hyperfunctional sirna
US6673661B1 (en) 2002-12-20 2004-01-06 Taiwan Semiconductor Manufacturing Co., Ltd. Self-aligned method for forming dual gate thin film transistor (TFT) device
US20040185559A1 (en) 2003-03-21 2004-09-23 Isis Pharmaceuticals Inc. Modulation of diacylglycerol acyltransferase 1 expression
US7723509B2 (en) 2003-04-17 2010-05-25 Alnylam Pharmaceuticals IRNA agents with biocleavable tethers
WO2004106356A1 (en) 2003-05-27 2004-12-09 Syddansk Universitet Functionalized nucleotide derivatives
EP1661905B9 (en) 2003-08-28 2012-12-19 IMANISHI, Takeshi Novel artificial nucleic acids of n-o bond crosslinkage type
WO2005027962A1 (en) 2003-09-18 2005-03-31 Isis Pharmaceuticals, Inc. 4’-thionucleosides and oligomeric compounds
AU2005252663B2 (en) 2004-06-03 2011-07-07 Isis Pharmaceuticals, Inc. Double strand compositions comprising differentially modified strands for use in gene modulation
EP2397563A3 (en) 2004-09-17 2012-07-18 Isis Pharmaceuticals, Inc. Enhanced antisense oligonucleotides
US20080261905A1 (en) 2004-11-08 2008-10-23 K.U. Leuven Research And Development Modified Nucleosides for Rna Interference
US20060148740A1 (en) 2005-01-05 2006-07-06 Prosensa B.V. Mannose-6-phosphate receptor mediated gene transfer into muscle cells
JP5342881B2 (ja) 2006-01-27 2013-11-13 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 6−修飾された二環式核酸類似体
AU2007249349B2 (en) 2006-05-11 2012-03-08 Isis Pharmaceuticals, Inc. 5'-Modified bicyclic nucleic acid analogs
US20100190837A1 (en) 2007-02-15 2010-07-29 Isis Pharmaceuticals, Inc. 5'-Substituted-2-F' Modified Nucleosides and Oligomeric Compounds Prepared Therefrom
EP2170917B1 (en) 2007-05-30 2012-06-27 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
CA2692579C (en) 2007-07-05 2016-05-03 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
WO2009082607A2 (en) 2007-12-04 2009-07-02 Alnylam Pharmaceuticals, Inc. Targeting lipids
WO2009100320A2 (en) 2008-02-07 2009-08-13 Isis Pharmaceuticals, Inc. Bicyclic cyclohexitol 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
NZ601660A (en) 2008-08-25 2014-05-30 Excaliard Pharmaceuticals Inc Antisense oligonucleotides directed against connective tissue growth factor and uses thereof
WO2010036698A1 (en) 2008-09-24 2010-04-01 Isis Pharmaceuticals, Inc. Substituted alpha-l-bicyclic nucleosides
US8604192B2 (en) 2008-09-24 2013-12-10 Isis Pharmaceuticals, Inc. Cyclohexenyl nucleic acids analogs
EP2462153B1 (en) 2009-08-06 2015-07-29 Isis Pharmaceuticals, Inc. Bicyclic cyclohexose nucleic acid analogs
CA2774389A1 (en) 2009-10-01 2011-04-07 Symphony Evolution, Inc. Methods of treating aneurysmal dilatation, blood vessel wall weakness and specifically abdominal aortic and thoracic aneurysm using matrix metalloprotease-2 inhibitors
KR101869570B1 (ko) 2010-04-28 2018-06-20 아이오니스 파마수티컬즈, 인코포레이티드 변형된 뉴클레오사이드 및 그로부터 제조된 올리고머 화합물
WO2012007327A1 (en) 2010-07-12 2012-01-19 Dkfz Deutsches Krebsforschungszentrum Wogonin for the prevention and therapy of cardiac hypertrophy
CA2812046A1 (en) 2010-09-15 2012-03-22 Alnylam Pharmaceuticals, Inc. Modified irna agents
CN102260673A (zh) * 2011-07-12 2011-11-30 深圳职业技术学院 靶向人血管紧张素原的rna干扰片段、表达载体与应用
EP3453761A1 (en) 2011-08-29 2019-03-13 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
EP3693460A1 (en) * 2012-07-27 2020-08-12 Ionis Pharmaceuticals, Inc. Modulation of renin-angiotensin system (ras) related diseases by angiotensinogen
CN103103192A (zh) * 2013-01-18 2013-05-15 深圳职业技术学院 靶向血管紧张素原的rna干扰片段、其表达载体、混合克隆细胞株及其应用
DK2991656T3 (da) 2013-05-01 2020-03-23 Ionis Pharmaceuticals Inc Sammensætninger og fremgangsmåder til modulering af apolipoprotein c-iii-ekspression
CN105164261B (zh) 2013-05-01 2022-03-18 莱古路斯治疗法股份有限公司 用于增强的细胞摄取的化合物和方法
CA3215908A1 (en) * 2014-05-22 2015-11-26 Alnylam Pharmaceuticals, Inc. Angiotensinogen (agt) irna compositions and methods of use thereof
US10709728B2 (en) * 2015-06-01 2020-07-14 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting angiotensinogen (AGT) and methods of use thereof

Also Published As

Publication number Publication date
US20190160090A1 (en) 2019-05-30
AU2024203439A1 (en) 2024-06-13
JP2023093644A (ja) 2023-07-04
IL295971A (en) 2022-10-01
JP2025011138A (ja) 2025-01-23
BR112018005223A2 (en) 2018-10-16
AU2016334114A1 (en) 2018-04-12
EP3359164A4 (en) 2019-06-12
EP3960183A1 (en) 2022-03-02
BR112018005223B1 (pt) 2022-08-09
AU2016334114B2 (en) 2022-01-27
CN108271351A (zh) 2018-07-10
KR20180055898A (ko) 2018-05-25
EP4474389A3 (en) 2025-03-19
CN113817735A (zh) 2021-12-21
CL2020001453A1 (es) 2020-11-13
WO2017062816A8 (en) 2018-01-11
CO2018002598A2 (es) 2018-06-12
EP4474389A2 (en) 2024-12-11
BR122020023854B1 (pt) 2022-11-29
PE20181085A1 (es) 2018-07-05
HK1258275A1 (zh) 2019-11-08
WO2017062816A3 (en) 2017-06-08
AU2022202671A1 (en) 2022-05-19
CN108271351B (zh) 2021-10-26
JP2022008677A (ja) 2022-01-13
IL257989A (en) 2018-05-31
JP2018530325A (ja) 2018-10-18
EP3359164A2 (en) 2018-08-15
CA2998898A1 (en) 2017-04-13
IL257989B (en) 2022-10-01
WO2017062816A2 (en) 2017-04-13
KR20240033305A (ko) 2024-03-12
IL257989B2 (en) 2023-02-01
MX392014B (es) 2025-03-21
US10912792B2 (en) 2021-02-09
SG10202003148VA (en) 2020-05-28
MY200263A (en) 2023-12-18
CL2018000899A1 (es) 2018-09-07
US20220000901A1 (en) 2022-01-06
MX2018004307A (es) 2018-05-01
MX2022005200A (es) 2022-05-18

Similar Documents

Publication Publication Date Title
IL286669A (en) Compounds and methods for modulating tmprss6 expression
ZA201801600B (en) Compounds and methods for modulating angiotensinogen expression
IL285229A (en) Compounds and methods for modulating RNA function
ZA201804070B (en) Eif4-a-inhibiting compounds and methods related thereto
PL3215147T3 (pl) Związki norketaminy osłabiającej działanie układu nerwowego i sposoby
IL251107A0 (en) Compounds and methods
GB201608779D0 (en) Methods and compounds
IL265139B (en) Dopamine-b-hydroxylase inhibitors
GB201612860D0 (en) Inhibitors
GB201507753D0 (en) New compounds and uses
GB201608776D0 (en) Methods and compounds
IL246718A0 (en) Hexahydrofuropyrroles as pde1 inhibitors
GB201501593D0 (en) New compounds and processes
IL253322A0 (en) bace1 inhibitors
GB201415250D0 (en) Compound and method
ZA201702526B (en) Chassis & method
GB2531269B (en) Tape application method
SG11201607445QA (en) Methods of modulating wars2
GB201516922D0 (en) New processes and compounds
GB201420773D0 (en) Compound and method
GB201415247D0 (en) Compound and method
GB201415254D0 (en) Compound and method
GB201509931D0 (en) Hyperthermia method
GB201406599D0 (en) Compound and method
GB201406595D0 (en) Compound and method