CR20190269A - COMPOSICIONES Y MÉTODOS PARA MODULAR LA EXPRESIÓN DE TTR Y VHB (Divisonal 2015-0612) - Google Patents

COMPOSICIONES Y MÉTODOS PARA MODULAR LA EXPRESIÓN DE TTR Y VHB (Divisonal 2015-0612)

Info

Publication number
CR20190269A
CR20190269A CR20190269A CR20190269A CR20190269A CR 20190269 A CR20190269 A CR 20190269A CR 20190269 A CR20190269 A CR 20190269A CR 20190269 A CR20190269 A CR 20190269A CR 20190269 A CR20190269 A CR 20190269A
Authority
CR
Costa Rica
Prior art keywords
conjugated
certain embodiments
compositions
methods
oligomeric compounds
Prior art date
Application number
CR20190269A
Other languages
English (en)
Inventor
Eric E Swayze
Punit P Seth
Thazha P Prakash
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=51843959&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CR20190269(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Ionis Pharmaceuticals Inc filed Critical Ionis Pharmaceuticals Inc
Publication of CR20190269A publication Critical patent/CR20190269A/es

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61K47/54—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 organic compound
    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
    • 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
    • A61K47/56—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • 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
    • 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
    • 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
    • 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
    • C07H21/04—Compounds 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
    • 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
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • 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
    • 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
    • C12N15/1137—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 against enzymes
    • 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)
    • C12Y301/03—Phosphoric monoester hydrolases (3.1.3)
    • C12Y301/03048—Protein-tyrosine-phosphatase (3.1.3.48)
    • 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
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C12N2310/113—Antisense targeting other non-coding nucleic acids, e.g. antagomirs
    • 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
    • C12N2310/17—Immunomodulatory nucleic acids
    • 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
    • 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
    • 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
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3511—Conjugate intercalating or cleaving agent
    • 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
    • C12N2310/3513—Protein; Peptide
    • 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
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol
    • 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
    • C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
    • C12N2310/3525—MOE, methoxyethoxy
    • 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
    • C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon
    • 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
    • C12N2320/30—Special therapeutic applications
    • C12N2320/32—Special delivery means, e.g. tissue-specific

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Virology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Peptides Or Proteins (AREA)
  • Steroid Compounds (AREA)
  • Liquid Crystal Substances (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Se proporcionan en la presente compuestos oligoméricos con grupos conjugados. En determinadas modalidades, los compuestos oligoméricos están conjugados a N-acetilgalactosaminaProvided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine. In certain embodiments, the present disclosure provides conjugated antisense compounds. In certain embodiments, the present disclosure provides conjugated antisense compounds comprising an antisense oligonucleotide complementary to a nucleic acid transcript of transthyretin (TTR).
CR20190269A 2013-05-01 2014-05-01 COMPOSICIONES Y MÉTODOS PARA MODULAR LA EXPRESIÓN DE TTR Y VHB (Divisonal 2015-0612) CR20190269A (es)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US201361818442P 2013-05-01 2013-05-01
US201361823826P 2013-05-15 2013-05-15
US201361843887P 2013-07-08 2013-07-08
US201361871673P 2013-08-29 2013-08-29
US201361880790P 2013-09-20 2013-09-20
US201461976991P 2014-04-08 2014-04-08
US201461986867P 2014-04-30 2014-04-30
PCT/US2014/036463 WO2014179627A2 (en) 2013-05-01 2014-05-01 Compositions and methods for modulating hbv and ttr expression

Publications (1)

Publication Number Publication Date
CR20190269A true CR20190269A (es) 2019-09-13

Family

ID=51843959

Family Applications (2)

Application Number Title Priority Date Filing Date
CR20190269A CR20190269A (es) 2013-05-01 2014-05-01 COMPOSICIONES Y MÉTODOS PARA MODULAR LA EXPRESIÓN DE TTR Y VHB (Divisonal 2015-0612)
CR20150612A CR20150612A (es) 2013-05-01 2015-11-12 Composiciones y métodos para modular la expresión de ttr y vhb

Family Applications After (1)

Application Number Title Priority Date Filing Date
CR20150612A CR20150612A (es) 2013-05-01 2015-11-12 Composiciones y métodos para modular la expresión de ttr y vhb

Country Status (35)

Country Link
US (24) US9714421B2 (es)
EP (11) EP2992098B1 (es)
JP (21) JP6387084B2 (es)
KR (16) KR20230113835A (es)
CN (11) CN114058617A (es)
AU (19) AU2014259756B2 (es)
BR (6) BR112015027377B1 (es)
CA (5) CA2921518A1 (es)
CL (2) CL2015003217A1 (es)
CR (2) CR20190269A (es)
CY (2) CY1121879T1 (es)
DK (4) DK2992098T3 (es)
DO (3) DOP2015000268A (es)
EA (2) EA031393B1 (es)
ES (4) ES2730015T3 (es)
HK (5) HK1221485A1 (es)
HR (2) HRP20190987T1 (es)
HU (2) HUE043697T2 (es)
IL (18) IL284593B2 (es)
LT (2) LT2992009T (es)
ME (1) ME03390B (es)
MX (11) MX2015015234A (es)
MY (2) MY178929A (es)
NZ (6) NZ728517A (es)
PE (2) PE20152002A1 (es)
PH (3) PH12015502493A1 (es)
PL (2) PL2992098T3 (es)
PT (3) PT2992009T (es)
RS (2) RS58981B1 (es)
RU (8) RU2699985C2 (es)
SG (5) SG10201801813YA (es)
SI (2) SI2992009T1 (es)
UA (2) UA120287C2 (es)
WO (5) WO2014179627A2 (es)
ZA (2) ZA201507216B (es)

Families Citing this family (436)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3335715A3 (en) 2008-10-15 2018-08-08 Ionis Pharmaceuticals, Inc. Modulation of factor 11 expression
CN102282155B (zh) 2008-12-02 2017-06-09 日本波涛生命科学公司 磷原子修饰的核酸的合成方法
US9744183B2 (en) 2009-07-06 2017-08-29 Wave Life Sciences Ltd. Nucleic acid prodrugs and methods of use thereof
DK2620428T3 (da) 2010-09-24 2019-07-01 Wave Life Sciences Ltd Asymmetrisk hjælpegruppe
JP6126009B2 (ja) 2010-11-17 2017-05-10 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． α−シヌクレイン発現の調節
DK2734208T3 (en) 2011-07-19 2017-06-19 Wave Life Sciences Ltd PROCEDURES FOR SYNTHESIS OF FUNCTIONALIZED NUCLEIC ACIDS
DK2751270T3 (en) 2011-08-29 2018-10-29 Ionis Pharmaceuticals Inc OLIGOMER-CONJUGATE COMPLEXES AND 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
EP3336189A1 (en) * 2012-04-20 2018-06-20 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
US20160002624A1 (en) 2012-05-17 2016-01-07 Isis Pharmaceuticals, Inc. Antisense oligonucleotide compositions
US9574193B2 (en) 2012-05-17 2017-02-21 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein (a) expression
RU2748495C2 (ru) * 2012-05-24 2021-05-26 Ионис Фармасьютикалз, Инк. Способы и композиции для модулирования экспрессии аполипопротеина (а)
CN104684923B (zh) 2012-07-13 2018-09-28 株式会社新日本科学 手性核酸佐剂
EP2872485B1 (en) 2012-07-13 2020-12-16 Wave Life Sciences Ltd. Asymmetric auxiliary group
RU2015104762A (ru) 2012-07-13 2018-08-31 Уэйв Лайф Сайенсес Лтд. Хиральный контроль
EP2920304B1 (en) * 2012-11-15 2019-03-06 Roche Innovation Center Copenhagen A/S Oligonucleotide conjugates
EP2951305B1 (en) * 2013-01-30 2018-08-15 F.Hoffmann-La Roche Ag Lna oligonucleotide carbohydrate conjugates
KR20200123263A (ko) * 2013-02-14 2020-10-28 아이오니스 파마수티컬즈, 인코포레이티드 지질단백질 리파제 결핍 (lpld) 모집단에서 아포지질단백질 c-iii (apociii) 발현의 조절
EP2992098B1 (en) 2013-05-01 2019-03-27 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating hbv and ttr expression
AU2014259954B2 (en) 2013-05-01 2019-11-07 Regulus Therapeutics Inc. MicroRNA compounds and methods for modulating miR-122
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
SG10201908122XA (en) * 2013-06-27 2019-10-30 Roche Innovation Ct Copenhagen As Antisense oligomers and conjugates targeting pcsk9
EP3019200B1 (en) * 2013-07-11 2022-03-23 Alnylam Pharmaceuticals, Inc. Oligonucleotide-ligand conjugates and process for their preparation
JP6617702B2 (ja) 2013-07-15 2019-12-11 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア Ｆｔｙ７２０のアザサイクリック拘束アナログ
TWI657819B (zh) 2013-07-19 2019-05-01 美商Ionis製藥公司 用於調節τ蛋白表現之組合物
US9943604B2 (en) 2013-09-20 2018-04-17 Ionis Pharmaceuticals, Inc. Targeted therapeutic nucleosides and their use
EP3052626A1 (en) * 2013-10-02 2016-08-10 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the lect2 gene
US11162096B2 (en) 2013-10-14 2021-11-02 Ionis Pharmaceuticals, Inc Methods for modulating expression of C9ORF72 antisense transcript
EP3060664B1 (en) 2013-10-25 2021-07-07 Sanofi Microrna compounds and methods for modulating mir-21 activity
MX2016005855A (es) * 2013-11-14 2016-07-13 Roche Innovation Ct Copenhagen As Compuestos de conjugados antisentido de apolipoproteina b (apob).
JP6482475B2 (ja) * 2014-01-07 2019-03-13 レナセラピューティクス株式会社 アンチセンスオリゴヌクレオチド及び糖誘導体を含む二本鎖オリゴヌクレオチド
WO2015108048A1 (ja) 2014-01-15 2015-07-23 株式会社新日本科学 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤
US10322173B2 (en) 2014-01-15 2019-06-18 Shin Nippon Biomedical Laboratories, Ltd. Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent
JPWO2015108047A1 (ja) 2014-01-15 2017-03-23 株式会社新日本科学 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤
PT3094728T (pt) 2014-01-16 2022-05-19 Wave Life Sciences Ltd Desenho quiral
JP6594902B2 (ja) 2014-02-11 2019-10-23 アルナイラム ファーマシューティカルズ， インコーポレイテッド ケトヘキソキナーゼ（ＫＨＫ）ｉＲＮＡ組成物及びその使用方法
EP3978610A3 (en) 2014-03-19 2022-08-24 Ionis Pharmaceuticals, Inc. Compositions for modulating ataxin 2 expression
US10006027B2 (en) 2014-03-19 2018-06-26 Ionis Pharmaceuticals, Inc. Methods for modulating Ataxin 2 expression
JP6622214B2 (ja) 2014-04-01 2019-12-18 バイオジェン・エムエイ・インコーポレイテッドＢｉｏｇｅｎ ＭＡ Ｉｎｃ． Ｓｏｄ−１発現を調節するための組成物
BR122020024443B1 (pt) * 2014-05-01 2022-02-22 Ionis Pharmaceuticals, Inc Composto e composição farmacêutica para modulação da expressão de angptl3
DK3137091T3 (da) 2014-05-01 2021-01-25 Ionis Pharmaceuticals Inc Konjugater af modificerede antisense-oligonukleotider og anvendelse deraf til modulation af pkk-ekspression
KR102369736B1 (ko) 2014-05-01 2022-03-02 아이오니스 파마수티컬즈, 인코포레이티드 보체 인자 b 발현을 조절하기 위한 조성물 및 방법
JP6667453B2 (ja) 2014-05-01 2020-03-18 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． 成長ホルモン受容体発現を調節するための組成物及び方法
EP4223315A3 (en) * 2014-05-01 2023-08-23 Ionis Pharmaceuticals, Inc. Method for synthesis of reactive conjugate clusters
GB201408623D0 (en) 2014-05-15 2014-07-02 Santaris Pharma As Oligomers and oligomer conjugates
AU2015264038B2 (en) 2014-05-22 2021-02-11 Alnylam Pharmaceuticals, Inc. Angiotensinogen (AGT) iRNA compositions and methods of use thereof
GB201410693D0 (en) 2014-06-16 2014-07-30 Univ Southampton Splicing modulation
US9487783B2 (en) 2014-08-07 2016-11-08 Regulus Therapeutics Inc. Targeting microRNAs for metabolic disorders
BR112017004056A2 (pt) 2014-09-12 2017-12-05 Biogen Ma Inc composições e métodos para detecção da proteína smn em um indivíduo e tratamento de um indivíduo
CN107109411B (zh) 2014-10-03 2022-07-01 冷泉港实验室 核基因输出的定向增加
WO2016055601A1 (en) 2014-10-10 2016-04-14 F. Hoffmann-La Roche Ag Galnac phosphoramidites, nucleic acid conjugates thereof and their use
WO2016061487A1 (en) * 2014-10-17 2016-04-21 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting aminolevulinic acid synthase-1 (alas1) and uses thereof
JOP20200092A1 (ar) 2014-11-10 2017-06-16 Alnylam Pharmaceuticals Inc تركيبات iRNA لفيروس الكبد B (HBV) وطرق لاستخدامها
JP2017535552A (ja) 2014-11-17 2017-11-30 アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． アポリポタンパク質Ｃ３（ＡＰＯＣ３）ｉＲＮＡ組成物およびその使用方法
JP2018504380A (ja) 2014-12-18 2018-02-15 アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． Ｒｅｖｅｒｓｉｒ（商標）化合物
WO2016112132A1 (en) 2015-01-06 2016-07-14 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of c9orf72 antisense transcript
US10538763B2 (en) 2015-01-16 2020-01-21 Ionis Pharmaceuticals, Inc. Compounds and methods for modulation of DUX4
AU2016219263B2 (en) 2015-02-13 2022-12-01 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (PNPLA3) iRNA compositions and methods of use thereof
AU2016217825B2 (en) 2015-02-15 2022-03-10 Arcturus Therapeutics, Inc. Acyl-amino-LNA and/or hydrocarbyl-amino-LNA oligonucleotides
US11129844B2 (en) 2015-03-03 2021-09-28 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating MECP2 expression
US10415038B2 (en) 2015-04-03 2019-09-17 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating TMPRSS6 expression
WO2016164746A1 (en) 2015-04-08 2016-10-13 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the lect2 gene
US10407678B2 (en) 2015-04-16 2019-09-10 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of C9ORF72 antisense transcript
WO2016172734A1 (en) 2015-04-24 2016-10-27 California Institute Of Technology Reactivation of x chromosome genes
WO2016205323A1 (en) 2015-06-18 2016-12-22 Alnylam Pharmaceuticals, Inc. Polynucleotde agents targeting hydroxyacid oxidase (glycolate oxidase, hao1) and methods of use thereof
WO2016209862A1 (en) 2015-06-23 2016-12-29 Alnylam Pharmaceuticals, Inc. Glucokinase (gck) irna compositions and methods of use thereof
JP2018519811A (ja) 2015-06-29 2018-07-26 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． 修飾ｃｒｉｓｐｒ ｒｎａ及び修飾単一ｃｒｉｓｐｒ ｒｎａならびにその使用
MY192997A (en) 2015-07-10 2022-09-20 Ionis Pharmaceuticals Inc Modulators of diacyglycerol acyltransferase 2 (dgat2)
WO2017011286A1 (en) 2015-07-10 2017-01-19 Alnylam Pharmaceuticals, Inc. Insulin-like growth factor binding protein, acid labile subunit (igfals) and insulin-like growth factor 1 (igf-1) irna compositions and methods of use thereof
US20180193471A1 (en) * 2015-07-16 2018-07-12 Kyowa Hakko Kirin Co., Ltd. ß2GPI GENE EXPRESSION-SUPPRESSING NUCLEIC ACID CONJUGATE
MA43072A (fr) 2015-07-22 2018-05-30 Wave Life Sciences Ltd Compositions d'oligonucléotides et procédés associés
CN107709342B (zh) 2015-08-06 2021-09-03 豪夫迈·罗氏有限公司 制备乙酰半乳糖胺酸衍生物的方法
CN105111118B (zh) * 2015-08-14 2017-04-12 天津小新医药科技有限公司 L‑薄荷醇类p2y12受体拮抗剂、制备方法及其用途
CN105111119B (zh) * 2015-08-14 2017-04-12 天津小新医药科技有限公司 一类卤代苯l‑薄荷醇类p2y12受体拮抗剂及其用途
US10633653B2 (en) 2015-08-14 2020-04-28 University Of Massachusetts Bioactive conjugates for oligonucleotide delivery
KR20180043819A (ko) 2015-08-24 2018-04-30 로슈 이노베이션 센터 코펜하겐 에이/에스 Lna-g 방법
KR20180051550A (ko) 2015-09-02 2018-05-16 알닐람 파마슈티칼스 인코포레이티드 프로그램된 세포사 1 리간드 1 (PD-L1) iRNA 조성물 및 그의 사용 방법
CA2999177A1 (en) 2015-09-24 2017-03-30 The Regents Of The University Of California Synthetic sphingolipid-like molecules, drugs, methods of their synthesis and methods of treatment
SG10201913209WA (en) 2015-09-24 2020-02-27 Ionis Pharmaceuticals Inc Modulators of kras expression
US20180273948A1 (en) * 2015-09-25 2018-09-27 Tarveda Therapeutics, Inc. RNAi CONJUGATES, PARTICLES AND FORMULATIONS THEREOF
EP3353305A4 (en) * 2015-09-25 2019-09-18 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
EP3353306A4 (en) 2015-09-25 2019-06-05 Ionis Pharmaceuticals, Inc. ANTISENSE CONJUGATED COMPOUNDS AND THEIR USE
EP4285912A3 (en) 2015-09-25 2024-07-10 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating ataxin 3 expression
JOP20210043A1 (ar) 2015-10-01 2017-06-16 Arrowhead Pharmaceuticals Inc تراكيب وأساليب لتثبيط تعبير جيني للـ lpa
US10577388B2 (en) 2015-10-02 2020-03-03 Roche Innovation Center Copenhagen A/S Oligonucleotide conjugation process
IL308174A (en) 2015-10-09 2024-01-01 Univ Southampton Gene expression modulation and dysregulated protein expression scanning
WO2017068087A1 (en) 2015-10-22 2017-04-27 Roche Innovation Center Copenhagen A/S Oligonucleotide detection method
EP3394258B1 (en) 2015-10-22 2021-09-22 Roche Innovation Center Copenhagen A/S In vitro toxicity screening assay
BR122023026882A2 (pt) 2015-11-06 2024-01-23 Ionis Pharmaceuticals, Inc Uso de um composto oligomérico
WO2017079745A1 (en) 2015-11-06 2017-05-11 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds for use in therapy
AR106683A1 (es) * 2015-11-16 2018-02-07 Hoffmann La Roche FOSFORAMIDITA DE AGRUPACIÓN DE GalNAc
WO2017096395A1 (en) 2015-12-04 2017-06-08 Ionis Pharmaceuticals, Inc. Methods of treating breast cancer
US11096956B2 (en) 2015-12-14 2021-08-24 Stoke Therapeutics, Inc. Antisense oligomers and uses thereof
EP3390636B1 (en) 2015-12-14 2021-05-19 Cold Spring Harbor Laboratory Antisense oligomers for treatment of dravet syndrome
CA3006599A1 (en) 2016-01-05 2017-07-13 Ionis Pharmaceuticals, Inc. Methods for reducing lrrk2 expression
WO2017123696A1 (en) 2016-01-12 2017-07-20 Interleukin Genetics, Inc. Methods for predicting response to treatment
AU2017211461B2 (en) 2016-01-26 2023-01-12 Nissan Chemical Corporation Single-stranded oligonucleotide
KR20180103166A (ko) 2016-01-29 2018-09-18 교와 핫꼬 기린 가부시키가이샤 핵산 복합체
EP3408391A4 (en) * 2016-01-31 2019-08-28 University of Massachusetts BRANCHED OLIGONUCLEOTIDES
EP3426261A4 (en) 2016-03-07 2020-03-25 Arrowhead Pharmaceuticals, Inc. TARGETED LIGANDS FOR THERAPEUTIC CONNECTIONS
AU2017229778A1 (en) 2016-03-09 2018-08-16 Ionis Pharmaceuticals, Inc. Methods and compositions for inhibiting PMP22 expression
RS61528B1 (sr) 2016-03-14 2021-04-29 Hoffmann La Roche Oligonukleotidi za smanjenje ekspresije pd-l1
AU2017234678A1 (en) 2016-03-16 2018-08-16 Ionis Pharmaceuticals, Inc. Methods of modulating KEAP1
WO2017161168A1 (en) 2016-03-16 2017-09-21 Ionis Pharmaceuticals, Inc. Modulation of dyrk1b expression
EP3228326A1 (en) * 2016-04-05 2017-10-11 Silence Therapeutics GmbH Nucleic acid linked to a trivalent glycoconjugate
MA45478A (fr) 2016-04-11 2019-02-20 Arbutus Biopharma Corp Compositions de conjugués d'acides nucléiques ciblés
CA3017532A1 (en) 2016-04-13 2017-10-19 Ionis Pharmaceuticals, Inc. Methods for reducing c9orf72 expression
WO2017178656A1 (en) 2016-04-14 2017-10-19 Roche Innovation Center Copenhagen A/S TRITYL-MONO-GalNAc COMPOUNDS AND THEIR USE
MA45295A (fr) 2016-04-19 2019-02-27 Alnylam Pharmaceuticals Inc Composition d'arni de protéine de liaison de lipoprotéines haute densité (hdlbp/vigiline) et procédés pour les utiliser
WO2017188898A1 (en) 2016-04-29 2017-11-02 Nanyang Technological University G-quadruplex-containing antisense oligonucleotides
MA45270A (fr) 2016-05-04 2017-11-09 Wave Life Sciences Ltd Compositions d'oligonucléotides et procédés associés
BR112018072362A2 (pt) 2016-05-06 2019-02-19 Ionis Pharmaceuticals, Inc. oligonucleotídeos conjugados a uma unidade de ligando do receptor glp-1 e seus usos
US11236339B2 (en) 2016-06-17 2022-02-01 Ionis Pharmaceuticals, Inc. Modulation of GYS1 expression
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
US11105794B2 (en) 2016-06-17 2021-08-31 Hoffmann-La Roche Inc. In vitro nephrotoxicity screening assay
CN109312403B (zh) 2016-06-17 2023-06-27 豪夫迈·罗氏有限公司 体外肾毒性筛选测定法
AU2017281497B2 (en) 2016-06-22 2023-04-06 Proqr Therapeutics Ii B.V. Single-stranded RNA-editing oligonucleotides
CN109415401B (zh) 2016-06-30 2023-02-03 协和麒麟株式会社 核酸复合物
AU2017296195A1 (en) 2016-07-11 2019-01-24 Translate Bio Ma, Inc. Nucleic acid conjugates and uses thereof
US10781175B2 (en) 2016-07-15 2020-09-22 Am Chemicals Llc Solid supports and phosphoramidite building blocks for oligonucleotide conjugates
SG11201900238UA (en) 2016-07-15 2019-02-27 Ionis Pharmaceuticals Inc Compounds and methods for modulation of smn2
CA3033368A1 (en) 2016-08-12 2018-02-15 University Of Massachusetts Conjugated oligonucleotides
JP2019532027A (ja) 2016-08-17 2019-11-07 ソルスティス バイオロジクス，リミティッド ポリヌクレオチド構築物
AU2017320582B2 (en) 2016-09-02 2023-11-16 Arrowhead Pharmaceuticals, Inc Targeting ligands
JOP20190065A1 (ar) 2016-09-29 2019-03-28 Ionis Pharmaceuticals Inc مركبات وطرق لتقليل التعبير عن tau
WO2018067900A1 (en) 2016-10-06 2018-04-12 Ionis Pharmaceuticals, Inc. Method of conjugating oligomeric compounds
JP2019537427A (ja) 2016-10-27 2019-12-26 カリフォルニア インスティチュート オブ テクノロジー Ｘ染色体の再活性化のためのｈｄａｃ阻害剤組成物
JOP20190104A1 (ar) 2016-11-10 2019-05-07 Ionis Pharmaceuticals Inc مركبات وطرق لتقليل التعبير عن atxn3
JP2019533472A (ja) * 2016-11-11 2019-11-21 ヤンセン バイオファーマ インク． Ｈｂｖ ｃｃｃｄｎａのオリゴヌクレオチド標的化戦略
TWI788312B (zh) 2016-11-23 2023-01-01 美商阿尼拉製藥公司 絲胺酸蛋白酶抑制因子Ａ１ ｉＲＮＡ組成物及其使用方法
JP2019535839A (ja) 2016-11-29 2019-12-12 ピュアテック ヘルス エルエルシー 治療剤の送達のためのエクソソーム
WO2018102745A1 (en) 2016-12-02 2018-06-07 Cold Spring Harbor Laboratory Modulation of lnc05 expression
CA3047076A1 (en) * 2016-12-13 2018-06-21 Am Sciences Inc Pharmaceutical composition for preventing or treating hepatitis b
KR20230166146A (ko) 2016-12-16 2023-12-06 알닐람 파마슈티칼스 인코포레이티드 트랜스티레틴(TTR) iRNA 조성물을 사용하여 TTR-관련 질병을 치료하거나 예방하는 방법
CN108239644B (zh) * 2016-12-23 2021-05-28 苏州瑞博生物技术股份有限公司 一种小干扰核酸和药物组合物及其用途
US10337070B2 (en) 2017-01-12 2019-07-02 Cardioforecast Ltd. Methods and kits for treating cardiovascular disease
US20200216845A1 (en) 2017-01-13 2020-07-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rela expression
EP3568480A1 (en) 2017-01-13 2019-11-20 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb2 expression
WO2018130585A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating relb expression
WO2018130583A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb1 expression
WO2018130582A1 (en) 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating rel expression
CN110337495B (zh) 2017-02-06 2024-03-29 日产化学株式会社 单链寡核苷酸
WO2018165564A1 (en) * 2017-03-09 2018-09-13 Ionis Pharmaceuticals, Inc. Morpholino modified oligomeric compounds
EP3594346A4 (en) 2017-03-10 2020-12-16 National Center For Child Health And Development ANTISENSE OLIGONUCLEOTIDE AND COMPOSITION FOR THE PREVENTION OR TREATMENT OF GLYCOGEN STORAGE DISEASE TYPE IA
JOP20190215A1 (ar) 2017-03-24 2019-09-19 Ionis Pharmaceuticals Inc مُعدّلات التعبير الوراثي عن pcsk9
DK3607069T3 (da) * 2017-04-05 2022-11-21 Silence Therapeutics Gmbh Produkter og sammensætninger
EP3385272A1 (en) * 2017-04-05 2018-10-10 Silence Therapeutics GmbH Further novel oligonucleotide-ligand conjugates
CN118460536A (zh) 2017-04-11 2024-08-09 阿布特斯生物制药公司 靶向组合物
SG11201909572QA (en) 2017-04-18 2019-11-28 Alnylam Pharmaceuticals Inc Methods for the treatment of subjects having a hepatitis b virus (hbv) infection
WO2018215049A1 (en) 2017-05-23 2018-11-29 F. Hoffmann-La Roche Ag Process for galnac oligonucleotide conjugates
US11273222B2 (en) * 2017-05-26 2022-03-15 National Cerebral And Cardiovascular Center Antisense nucleic acid targeting PCSK9
CN111050806A (zh) 2017-06-02 2020-04-21 波涛生命科学有限公司 寡核苷酸组合物及其使用方法
WO2018223073A1 (en) * 2017-06-02 2018-12-06 Wave Life Sciences Ltd. Oligonucleotide compositions and methods of use thereof
US11401519B2 (en) 2017-06-07 2022-08-02 University Of Massachusetts Anti-ADAM33 oligonucleotides and related methods
JP7406793B2 (ja) 2017-06-23 2023-12-28 ユニバーシティー オブ マサチューセッツ ２テイル自己デリバリー型ｓｉＲＮＡおよび関連方法
CA3069868A1 (en) 2017-07-13 2019-01-17 Alnylam Pharmaceuticals Inc. Lactate dehydrogenase a (ldha) irna compositions and methods of use thereof
BR112020001430A2 (pt) 2017-07-26 2020-07-28 Nissan Chemical Corporation oligonucleotídeo de fita simples
WO2019027009A1 (ja) * 2017-08-02 2019-02-07 協和発酵キリン株式会社 核酸複合体
WO2019027015A1 (ja) * 2017-08-02 2019-02-07 協和発酵キリン株式会社 核酸複合体
WO2019030313A2 (en) 2017-08-11 2019-02-14 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF UBE3C EXPRESSION
CA3073213A1 (en) 2017-08-17 2019-02-21 Alnylam Pharmaceuticals, Inc. Tunable reversir tm compounds
AU2018318231A1 (en) 2017-08-18 2020-02-13 Ionis Pharmaceuticals, Inc. Modulation of the notch signaling pathway for treatment of respiratory disorders
WO2019038228A1 (en) 2017-08-22 2019-02-28 Roche Innovation Center Copenhagen A/S OLIGONUCLEOTIDES FOR MODULATION OF TOM1 EXPRESSION
GB2599884B (en) 2017-08-25 2022-08-31 Stoke Therapeutics Inc Antisense oligomers for treatment of conditions and diseases
US10517889B2 (en) 2017-09-08 2019-12-31 Ionis Pharmaceuticals, Inc. Modulators of SMAD7 expression
SG11202002149XA (en) * 2017-09-14 2020-04-29 Janssen Biopharma Inc Galnac derivatives
US20190098879A1 (en) 2017-09-29 2019-04-04 Regeneron Pharmaceuticals, Inc. Non-Human Animals Comprising A Humanized TTR Locus And Methods Of Use
WO2019067872A1 (en) 2017-09-29 2019-04-04 Intellia Therapeutics, Inc. COMPOSITIONS AND METHODS FOR EDITING THE TTR GENE AND TREATING AMYLOID DOSE ATTR
CN111226114A (zh) 2017-10-13 2020-06-02 罗氏创新中心哥本哈根有限公司 用部分立体限定的寡核苷酸子文库鉴定反义寡核苷酸改进的立体限定硫代磷酸酯寡核苷酸变体的方法
UA126931C2 (uk) 2017-10-16 2023-02-22 Ф. Хоффманн-Ля Рош Аг МОЛЕКУЛИ НУКЛЕЇНОВИХ КИСЛОТ ДЛЯ ЗМЕНШЕННЯ РІВНЯ мРНК PAPD5 І PAPD7 ДЛЯ ЛІКУВАННЯ ІНФЕКЦІЙНОГО ГЕПАТИТУ B
WO2019089922A1 (en) 2017-11-01 2019-05-09 Alnylam Pharmaceuticals, Inc. Complement component c3 irna compositions and methods of use thereof
TWI809004B (zh) 2017-11-09 2023-07-21 美商Ionis製藥公司 用於降低snca表現之化合物及方法
US20200385719A1 (en) 2017-11-16 2020-12-10 Alnylam Pharmaceuticals, Inc. Kisspeptin 1 (kiss1) irna compositions and methods of use thereof
WO2019100039A1 (en) 2017-11-20 2019-05-23 Alnylam Pharmaceuticals, Inc. Serum amyloid p component (apcs) irna compositions and methods of use thereof
JP7360716B2 (ja) * 2017-12-01 2023-10-13 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド 核酸、当該核酸を含む組成物および複合体ならびに調製方法と使用
CN111050807B (zh) * 2017-12-01 2024-05-28 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
CN110945131B (zh) * 2017-12-01 2024-05-28 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
CN118291456A (zh) 2017-12-01 2024-07-05 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
EP3719126A4 (en) * 2017-12-01 2021-10-20 Suzhou Ribo Life Science Co., Ltd. NUCLEIC ACID, COMPOSITION AND CONJUGATE CONTAINING NUCLEIC ACID, ASSOCIATED PREPARATION PROCESS AND USE
US11414665B2 (en) 2017-12-01 2022-08-16 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, composition and conjugate comprising the same, and preparation method and use thereof
WO2019105418A1 (zh) 2017-12-01 2019-06-06 苏州瑞博生物技术有限公司 双链寡核苷酸、含双链寡核苷酸的组合物与缀合物及制备方法和用途
WO2019115416A2 (en) 2017-12-11 2019-06-20 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating fndc3b expression
WO2019115417A2 (en) 2017-12-12 2019-06-20 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating rb1 expression
US11725208B2 (en) 2017-12-14 2023-08-15 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
US20200308588A1 (en) 2017-12-18 2020-10-01 Alnylam Pharmaceuticals, Inc. High mobility group box-1 (hmgb1) irna compositions and methods of use thereof
EP3729095A1 (en) 2017-12-21 2020-10-28 F. Hoffmann-La Roche AG Companion diagnostic for htra1 rna antagonists
WO2019126641A2 (en) 2017-12-21 2019-06-27 Ionis Pharmaceuticals, Inc. Modulation of frataxin expression
EP4092117A1 (en) 2017-12-22 2022-11-23 Roche Innovation Center Copenhagen A/S Gapmer oligonucleotides comprising a phosphorodithioate internucleoside linkage
JP7476102B2 (ja) 2017-12-22 2024-04-30 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 ホスホロジチオアートヌクレオシド間結合を含むオリゴヌクレオチド
EP3728590A1 (en) 2017-12-22 2020-10-28 Roche Innovation Center Copenhagen A/S Novel thiophosphoramidites
CN109957566B (zh) * 2017-12-26 2023-08-25 广州市锐博生物科技有限公司 修饰的寡核苷酸和可用于合成修饰的寡核苷酸的化合物
AU2017444369B2 (en) * 2017-12-26 2022-02-24 Guangzhou Ribobio Co., Ltd. Modified oligonucleotides and compound that can be used for synthesizing same
AU2018394875B2 (en) * 2017-12-29 2023-08-03 Suzhou Ribo Life Science Co., Ltd. Conjugates and preparation and use thereof
EP3737758A1 (en) 2018-01-10 2020-11-18 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating pias4 expression
EP3737424A4 (en) * 2018-01-10 2021-10-27 Translate Bio MA, Inc. COMPOSITIONS AND METHODS FOR FACILITATING THE DELIVERY OF SYNTHETIC NUCLEIC ACIDS TO CELLS
US20220119811A1 (en) 2018-01-12 2022-04-21 Roche Innovation Center Copenhagen A/S Alpha-synuclein antisense oligonucleotides and uses thereof
JP7455746B2 (ja) 2018-01-12 2024-03-26 ブリストル－マイヤーズ スクイブ カンパニー アルファ－シヌクレインを標的とするアンチセンスオリゴヌクレオチドおよびその使用
EP3737760A1 (en) 2018-01-12 2020-11-18 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating gsk3b expression
PE20211749A1 (es) 2018-01-12 2021-09-06 Bristol Myers Squibb Co Oligonucleotidos antisentido que actuan sobre alfa-sinucleina, y usos de estos
MX2020007369A (es) 2018-01-15 2020-10-28 Ionis Pharmaceuticals Inc Moduladores de la expresion de dnm2.
US20210095276A1 (en) 2018-01-17 2021-04-01 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating erc1 expression
JP2021511029A (ja) 2018-01-18 2021-05-06 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 Ｓｒｅｂｐ１を標的とするアンチセンスオリゴヌクレオチド
WO2019145386A1 (en) 2018-01-26 2019-08-01 Roche Innovation Center Copenhagen A/S Oligonucleotides for modulating csnk1d expression
AU2019218987A1 (en) 2018-02-12 2020-07-23 Ionis Pharmaceuticals, Inc. Modified compounds and uses thereof
CA3090517A1 (en) 2018-02-14 2019-08-22 Deep Genomics Incorporated Oligonucleotide therapy for wilson disease
BR112020016347A2 (pt) 2018-02-21 2021-01-12 Bristol-Myers Squibb Company Oligonucleotídeos antisense de camk2d e seus usos
US11732260B2 (en) 2018-03-02 2023-08-22 Ionis Pharmaceuticals, Inc. Compounds and methods for the modulation of amyloid-β precursor protein
TWI840345B (zh) 2018-03-02 2024-05-01 美商Ionis製藥公司 Irf4表現之調節劑
US11958878B2 (en) 2018-03-09 2024-04-16 Daiichi Sankyo Company, Limited Therapeutic agent for glycogen storage disease type IA
US11661601B2 (en) 2018-03-22 2023-05-30 Ionis Pharmaceuticals, Inc. Methods for modulating FMR1 expression
CA3097544A1 (en) 2018-04-05 2019-10-10 F. Hoffmann-La Roche Ag Use of fubp1 inhibitors for treating hepatitis b virus infection
JP7275164B2 (ja) 2018-04-11 2023-05-17 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 Ｅｚｈ２発現の調節因子
JP2021523227A (ja) 2018-05-04 2021-09-02 ストーク セラピューティクス，インク． コレステリルエステル蓄積症の処置のための方法及び組成物
JP2021522808A (ja) 2018-05-07 2021-09-02 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 オリゴヌクレオチド治療剤の超並列発見方法
US12005120B2 (en) 2018-05-08 2024-06-11 Regulus Therapeutics Inc. Galnac conjugated modified oligonucleotides as miR-122 inhibitor having HCV antiviral activity with reduced hyperbilirubinemia side-effect
MX2020011913A (es) * 2018-05-09 2021-01-29 Ionis Pharmaceuticals Inc Compuestos y metodos para la reduccion de la expresion de fxi.
CR20200604A (es) 2018-05-09 2021-02-09 Ionis Pharmaceuticals Inc Compuestos y métodos para reducir de la expresión de atxn3
FI3794122T3 (fi) 2018-05-14 2023-11-07 Alnylam Pharmaceuticals Inc Angiotensinogeenin (AGT) IRNA-koostumuksia ja niiden käyttömenetelmä
CA3103429A1 (en) 2018-06-14 2019-12-19 Don W. Cleveland Compounds and methods for increasing stmn2 expression
TWI833770B (zh) 2018-06-27 2024-03-01 美商Ionis製藥公司 用於減少 lrrk2 表現之化合物及方法
MX2020013366A (es) 2018-07-03 2021-03-09 Hoffmann La Roche Oligonucleotidos para modular la expresion de tau.
WO2020007826A1 (en) 2018-07-05 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting mbtps1
WO2020011745A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers6
WO2020011744A2 (en) 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers5
BR112021000538A2 (pt) 2018-07-13 2021-04-06 F. Hoffmann-La Roche Ag Oligonucleotídeos para modular a expressão de rtel1
AU2019310097A1 (en) 2018-07-25 2021-02-04 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing ATXN2 expression
WO2020025563A1 (en) 2018-07-31 2020-02-06 Roche Innovation Center Copenhagen A/S Oligonucleotides comprising a phosphorotrithioate internucleoside linkage
JP2021532075A (ja) 2018-07-31 2021-11-25 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 ホスホロトリチオエートヌクレオシド間結合を含むオリゴヌクレオチド
WO2020033748A1 (en) 2018-08-08 2020-02-13 Arcturus Therapeutics, Inc. Compositions and agents against nonalcoholic steatohepatitis
SG11202101288TA (en) 2018-08-10 2021-03-30 Univ Massachusetts Modified oligonucleotides targeting snps
MX2021001056A (es) 2018-08-13 2021-04-12 Alnylam Pharmaceuticals Inc Composiciones de agente de acido ribonucleico bicatenario (arnbc) de virus de la hepatitis b (vhb) y metodos de uso de las mismas.
EP3842534A4 (en) 2018-08-21 2022-07-06 Suzhou Ribo Life Science Co., Ltd. NUCLEIC ACID, COMPOSITION AND CONJUGATE CONTAINING NUCLEIC ACID AND METHOD OF USE THEREOF
EP3844274A1 (en) 2018-08-28 2021-07-07 Roche Innovation Center Copenhagen A/S Neoantigen engineering using splice modulating compounds
WO2020060986A1 (en) 2018-09-18 2020-03-26 Alnylam Pharmaceuticals, Inc. Ketohexokinase (khk) irna compositions and methods of use thereof
TW202023573A (zh) 2018-09-19 2020-07-01 美商Ionis製藥公司 Pnpla3表現之調節劑
CN111655297A (zh) * 2018-09-30 2020-09-11 苏州瑞博生物技术有限公司 一种siRNA缀合物及其制备方法和用途
WO2020077390A1 (en) * 2018-10-18 2020-04-23 Murdoch University Antisense therapy for ptp1b related conditions
US10913951B2 (en) 2018-10-31 2021-02-09 University of Pittsburgh—of the Commonwealth System of Higher Education Silencing of HNF4A-P2 isoforms with siRNA to improve hepatocyte function in liver failure
US20210395737A1 (en) 2018-11-09 2021-12-23 Novartis Ag Method for reducing the risk of a cardiovascular event with conjugated antisense compounds targeting apo(a)
TW202028222A (zh) 2018-11-14 2020-08-01 美商Ionis製藥公司 Foxp3表現之調節劑
EA202191342A1 (ru) 2018-11-15 2021-08-10 Айонис Фармасьютикалз, Инк. Модуляторы экспрессии irf5
TWI841633B (zh) 2018-11-21 2024-05-11 美商Ionis製藥公司 用於減少朊病毒表現之化合物及方法
EP3884051A2 (en) 2018-11-23 2021-09-29 Sanofi Novel rna compositions and methods for inhibiting angptl8
WO2020111280A1 (ja) 2018-11-30 2020-06-04 協和キリン株式会社 核酸複合体
JP2022515744A (ja) 2018-12-20 2022-02-22 プラクシス プレシジョン メディシンズ， インコーポレイテッド Ｋｃｎｔ１関連障害の治療のための組成物及び方法
US20220062427A1 (en) * 2018-12-28 2022-03-03 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, composition and conjugate containing nucleic acid, preparation method therefor and use thereof
GB201821269D0 (en) 2018-12-28 2019-02-13 Nippon Shinyaku Co Ltd Myostatin signal inhibitor
CN111377985B (zh) * 2018-12-29 2023-11-10 苏州瑞博生物技术股份有限公司 化合物和缀合物及其制备方法和用途
CN113330117B (zh) * 2019-01-18 2024-05-28 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
BR112021013369A2 (pt) 2019-01-31 2021-09-21 Ionis Pharmaceuticals, Inc. Moduladores de expressão de yap1
CN113474352A (zh) 2019-02-20 2021-10-01 罗氏创新中心哥本哈根有限公司 新型亚磷酰胺
TW202102516A (zh) 2019-02-20 2021-01-16 丹麥商羅氏創新中心哥本哈根有限公司 膦醯基乙酸酯間隙子寡核苷酸
CN109799330B (zh) * 2019-02-22 2021-03-02 华中科技大学同济医学院附属同济医院 神经氨酸及神经氨酸酶抑制剂在慢性心力衰竭中的应用
WO2020173845A1 (en) 2019-02-26 2020-09-03 Roche Innovation Center Copenhagen A/S Oligonucleotide formulation method
US11279932B2 (en) 2019-02-27 2022-03-22 Ionis Pharmaceuticals, Inc. Modulators of MALAT1 expression
EP3931323A4 (en) * 2019-02-28 2023-04-05 Deep Genomics Incorporated LIGAND AGGREGATES AND METHODS OF USE AND PREPARATION
JP7550165B2 (ja) 2019-03-29 2024-09-12 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 Ｕｂｅ３ａ－ａｔｓを調節するための化合物及び方法
EP3947678A1 (en) 2019-04-02 2022-02-09 ProQR Therapeutics II B.V. Antisense oligonucleotides for immunotherapy
WO2020206115A2 (en) 2019-04-03 2020-10-08 Bristol-Myers Squibb Company Angptl2 antisense oligonucleotides and uses thereof
WO2020233650A1 (zh) 2019-05-22 2020-11-26 苏州瑞博生物技术股份有限公司 核酸、药物组合物与缀合物及制备方法和用途
WO2020233651A1 (zh) 2019-05-22 2020-11-26 苏州瑞博生物技术股份有限公司 核酸、药物组合物与缀合物及制备方法和用途
CN118252843A (zh) 2019-05-22 2024-06-28 苏州瑞博生物技术股份有限公司 核酸、药物组合物与缀合物及制备方法和用途
US20230313195A1 (en) 2019-05-22 2023-10-05 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition, conjugate, preparation method, and use
JP2022534069A (ja) 2019-05-24 2022-07-27 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド 核酸、薬物組成物及び複合体並びに調製方法と使用
EP3978609A4 (en) 2019-05-24 2024-02-07 Suzhou Ribo Life Science Co., Ltd. NUCLEIC ACID, PHARMACEUTICAL COMPOSITION, CONJUGATE, PROCESS OF PREPARATION AND USE
US20220186221A1 (en) 2019-05-24 2022-06-16 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition and conjugate, preparation method and use
EP3976791A4 (en) 2019-05-28 2023-10-11 Ionis Pharmaceuticals, Inc. COMPOUNDS AND METHODS FOR REDUCING FOOT EXPRESSION
US11466274B2 (en) 2019-05-31 2022-10-11 Aligos Therapeutics, Inc. Modified gapmer oligonucleotides and methods of use
CA3137761A1 (en) 2019-06-04 2020-12-10 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ttr locus with a beta-slip mutation and methods of use
EP3990465A1 (en) 2019-06-25 2022-05-04 Amgen Inc. Purification methods for carbohydrate-linked oligonucleotides
WO2021021673A1 (en) 2019-07-26 2021-02-04 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating gfap
WO2021022109A1 (en) 2019-08-01 2021-02-04 Alnylam Pharmaceuticals, Inc. SERPIN FAMILY F MEMBER 2 (SERPINF2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
WO2021022108A2 (en) 2019-08-01 2021-02-04 Alnylam Pharmaceuticals, Inc. CARBOXYPEPTIDASE B2 (CPB2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
JP2022547790A (ja) 2019-08-09 2022-11-16 ユニバーシティー オブ マサチューセッツ Ｓｎｐを標的とする化学修飾オリゴヌクレオチド
EP4013870A1 (en) 2019-08-13 2022-06-22 Alnylam Pharmaceuticals, Inc. Small ribosomal protein subunit 25 (rps25) irna agent compositions and methods of use thereof
CN114555621A (zh) * 2019-08-15 2022-05-27 Ionis制药公司 键修饰的寡聚化合物及其用途
JP2022546040A (ja) 2019-08-27 2022-11-02 サノフイ Ｐｃｓｋ９を阻害するための組成物および方法
EP4023659A4 (en) 2019-08-29 2024-02-28 Suzhou Ribo Life Science Co., Ltd. COMPOUND AND DRUG CONJUGATE, PRODUCTION METHOD AND USE THEREOF
EP4022062A1 (en) 2019-08-30 2022-07-06 Alnylam Pharmaceuticals, Inc. Neurofilament light chain (nfl) as a biomarker for transthyretin amyloidosis polyneuropathy
WO2021046260A1 (en) 2019-09-03 2021-03-11 Arcturus Therapeutics, Inc. Asialoglycoprotein receptor mediated delivery of therapeutically active conjugates
US20220378920A1 (en) * 2019-09-10 2022-12-01 Daiichi Sankyo Company, Limited CONJUGATE OF GalNAc-OLIGONUCLEOTIDE FOR DELIVERY TO LIVER AND MANUFACTURING METHOD THEREOF
TW202126304A (zh) 2019-09-20 2021-07-16 瑞士商赫孚孟拉羅股份公司 使用核心蛋白異位調節劑治療hbv感染之方法
EP4045062A1 (en) 2019-10-14 2022-08-24 Astrazeneca AB Modulators of pnpla3 expression
EP4045652A1 (en) 2019-10-18 2022-08-24 Alnylam Pharmaceuticals, Inc. Solute carrier family member irna compositions and methods of use thereof
JP2022553348A (ja) 2019-10-22 2022-12-22 アルナイラム ファーマシューティカルズ， インコーポレイテッド 補体成分Ｃ３ ｉＲＮＡ組成物およびその使用方法
TW202132567A (zh) 2019-11-01 2021-09-01 美商阿尼拉製藥公司 亨汀頓蛋白（ＨＴＴ）ｉＲＮＡ劑組成物及其使用方法
BR112022009216A2 (pt) 2019-11-13 2022-08-02 Alnylam Pharmaceuticals Inc Métodos e composições para tratar um distúrbio associado a angiotensinogênio (agt)
EP4061945A1 (en) 2019-11-22 2022-09-28 Alnylam Pharmaceuticals, Inc. Ataxin3 (atxn3) rnai agent compositions and methods of use thereof
CN112876534B (zh) * 2019-11-29 2024-02-09 苏州瑞博生物技术股份有限公司 肝靶向化合物及缀合物
TW202140509A (zh) 2019-12-13 2021-11-01 美商阿尼拉製藥公司 人類染色體９開讀框７２（Ｃ９ＯＲＦ７２）ｉＲＮＡ劑組成物及其使用方法
TW202138559A (zh) 2019-12-16 2021-10-16 美商阿尼拉製藥公司 含類ＰＡＴＡＴＩＮ磷脂酶結構域３（ＰＮＰＬＡ３）ｉＲＮＡ組成物及其使用方法
CN111041025B (zh) * 2019-12-17 2021-06-18 深圳市瑞吉生物科技有限公司 基于结合N-乙酰半乳糖胺多肽的mRNA靶向分子及其制备方法
CN114901821A (zh) 2019-12-19 2022-08-12 豪夫迈·罗氏有限公司 Sept9抑制剂用于治疗乙型肝炎病毒感染的用途
WO2021122993A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of saraf inhibitors for treating hepatitis b virus infection
JP2023506550A (ja) 2019-12-19 2023-02-16 エフ． ホフマン－ラ ロシュ エージー． Ｂ型肝炎ウイルス感染症を処置するためのｓｂｄｓ阻害剤の使用
CN114829599A (zh) 2019-12-19 2022-07-29 豪夫迈·罗氏有限公司 Scamp3抑制剂用于治疗乙型肝炎病毒感染的用途
WO2021122921A1 (en) 2019-12-19 2021-06-24 F. Hoffmann-La Roche Ag Use of cops3 inhibitors for treating hepatitis b virus infection
US20230044958A1 (en) 2019-12-24 2023-02-09 Hoffmann-La Roche Inc. Method of treating virus infection using a tlr7 agonist
TW202137987A (zh) 2019-12-24 2021-10-16 瑞士商赫孚孟拉羅股份公司 用於治療ｈｂｖ之靶向ｈｂｖ的治療性寡核苷酸及ｔｌｒ７促效劑之醫藥組合
JP2023509872A (ja) 2019-12-24 2023-03-10 エフ． ホフマン－ラ ロシュ アーゲー Ｈｂｖを標的とする抗ウイルス剤及び／又はｈｂｖの処置のための免疫調節剤の医薬組合せ
CN114929729A (zh) * 2020-01-30 2022-08-19 卫材R&D管理有限公司 核酸复合体及包含该核酸复合体的医药组合物
MX2022009763A (es) 2020-02-10 2022-09-09 Alnylam Pharmaceuticals Inc Composiciones y metodos para silenciar la expresion del factor de crecimiento endotelial vascular a (vegf-a).
WO2021167841A1 (en) 2020-02-18 2021-08-26 Alnylam Pharmaceuticals, Inc. Apolipoprotein c3 (apoc3) irna compositions and methods of use thereof
AU2021225957A1 (en) 2020-02-28 2022-09-08 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating SMN2
WO2021178607A1 (en) 2020-03-05 2021-09-10 Alnylam Pharmaceuticals, Inc. Complement component c3 irna compositions and methods of use thereof for treating or preventing complement component c3-associated diseases
BR112022017822A2 (pt) 2020-03-06 2022-11-08 Alnylam Pharmaceuticals Inc Composições de irna de cetoexocinase (khk) e métodos de uso das mesmas
CN115461460A (zh) 2020-03-06 2022-12-09 阿尔尼拉姆医药品有限公司 用于抑制转甲状腺素蛋白(ttr)的表达的组合物和方法
WO2021188611A1 (en) 2020-03-18 2021-09-23 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating subjects having a heterozygous alanine-glyoxylate aminotransferase gene (agxt) variant
EP4126967A1 (en) 2020-03-23 2023-02-08 Amgen Inc. Monoclonal antibodies to chemically-modified nucleic acids and uses thereof
JP2023519274A (ja) 2020-03-26 2023-05-10 アルナイラム ファーマシューティカルズ， インコーポレイテッド コロナウイルスｉＲＮＡ組成物およびその使用方法
CN115485381A (zh) * 2020-03-26 2022-12-16 国立研究开发法人国立循环器病研究中心 以apoc3为靶点的反义核酸
AR121769A1 (es) 2020-04-06 2022-07-06 Alnylam Pharmaceuticals Inc Composiciones y métodos para el silenciamiento de la expresión de myoc
WO2021206922A1 (en) 2020-04-07 2021-10-14 Alnylam Pharmaceuticals, Inc. Transmembrane serine protease 2 (tmprss2) irna compositions and methods of use thereof
WO2021206917A1 (en) 2020-04-07 2021-10-14 Alnylam Pharmaceuticals, Inc. ANGIOTENSIN-CONVERTING ENZYME 2 (ACE2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
IL297130A (en) 2020-04-07 2022-12-01 Alnylam Pharmaceuticals Inc Compositions and methods for silencing scn9a expression
BR112022021813A2 (pt) 2020-04-27 2023-01-17 Alnylam Pharmaceuticals Inc Composições de agente de apolipoproteína e (apoe) irna e métodos de uso das mesmas
CN111575279A (zh) * 2020-04-27 2020-08-25 江苏为真生物医药技术股份有限公司 利用asgpr小分子配体特异性捕获肝细胞外囊泡或循环肿瘤细胞的方法
IL297680A (en) 2020-04-30 2022-12-01 Alnylam Pharmaceuticals Inc IRNA compounds complement factor b (cfb) and methods of using them
MX2022013707A (es) 2020-05-01 2022-12-07 Ionis Pharmaceuticals Inc Compuestos y metodos para modular atxn1.
KR20230022409A (ko) 2020-05-11 2023-02-15 스톡 테라퓨틱스, 인크. 병태 및 질환의 치료를 위한 opa1 안티센스 올리고머
WO2021231675A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of argininosuccinate synthetase (ass1)
WO2021231691A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of retinoschisin 1 (rsi)
EP4150076A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of methyl-cpg binding protein 2 (mecp2)
WO2021231692A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of otoferlin (otof)
WO2021231673A1 (en) 2020-05-15 2021-11-18 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of leucine rich repeat kinase 2 (lrrk2)
EP4150087A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of gap junction protein beta 2 (gjb2)
EP4150078A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of argininosuccinate lyase (asl)
EP4150077A1 (en) 2020-05-15 2023-03-22 Korro Bio, Inc. Methods and compositions for the adar-mediated editing of transmembrane channel-like protein 1 (tmc1)
US11408000B2 (en) 2020-06-03 2022-08-09 Triplet Therapeutics, Inc. Oligonucleotides for the treatment of nucleotide repeat expansion disorders associated with MSH3 activity
WO2021252557A1 (en) 2020-06-09 2021-12-16 Alnylam Pharmaceuticals, Inc. Rnai compositions and methods of use thereof for delivery by inhalation
WO2021249484A1 (zh) * 2020-06-10 2021-12-16 南京明德新药研发有限公司 缀合基团及其缀合物
EP4168546A1 (en) 2020-06-18 2023-04-26 Alnylam Pharmaceuticals, Inc. Xanthine dehydrogenase (xdh) irna compositions and methods of use thereof
AR122731A1 (es) 2020-06-26 2022-10-05 Hoffmann La Roche Oligonucleótidos mejorados para modular la expresión de fubp1
TW202216996A (zh) 2020-06-29 2022-05-01 美商Ionis製藥公司 調節ｐｌｐ１之化合物及方法
CN111744019B (zh) 2020-07-01 2023-08-04 深圳瑞吉生物科技有限公司 基于甘露糖的mRNA靶向递送系统及其应用
AU2021305665A1 (en) 2020-07-10 2023-02-23 Centre National De La Recherche Scientifique Methods and compositions for treating epilepsy
CR20230126A (es) * 2020-08-13 2023-05-03 Amgen Inc CONSTRUCCIONES DE iARN Y MÉTODOS PARA INHIBIR LA EXPRESIÓN DE MARC1
EP4200419A2 (en) 2020-08-21 2023-06-28 F. Hoffmann-La Roche AG Use of a1cf inhibitors for treating hepatitis b virus infection
WO2022066847A1 (en) 2020-09-24 2022-03-31 Alnylam Pharmaceuticals, Inc. Dipeptidyl peptidase 4 (dpp4) irna compositions and methods of use thereof
JP2023544413A (ja) 2020-10-05 2023-10-23 アルナイラム ファーマシューティカルズ， インコーポレイテッド Ｇタンパク質共役受容体７５（ＧＰＲ７５）ｉＲＮＡ組成物およびその使用方法
WO2022079222A1 (en) 2020-10-16 2022-04-21 Sanofi Novel rna compositions and methods for inhibiting angptl3
US20240035029A1 (en) 2020-10-16 2024-02-01 Sanofi Rna compositions and methods for inhibiting lipoprotein(a)
WO2022087329A1 (en) 2020-10-23 2022-04-28 Alnylam Pharmaceuticals, Inc. Mucin 5b (muc5b) irna compositions and methods of use thereof
WO2022103999A1 (en) 2020-11-13 2022-05-19 Alnylam Pharmaceuticals, Inc. COAGULATION FACTOR V (F5) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
CA3201661A1 (en) 2020-11-18 2022-05-27 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating angiotensinogen expression
US20240002853A1 (en) 2020-11-23 2024-01-04 Alpha Anomeric Sas Nucleic acid duplexes
EP4259795A1 (en) 2020-12-08 2023-10-18 Alnylam Pharmaceuticals, Inc. Coagulation factor x (f10) irna compositions and methods of use thereof
GB2603454A (en) 2020-12-09 2022-08-10 Ucl Business Ltd Novel therapeutics for the treatment of neurodegenerative disorders
WO2022133278A2 (en) 2020-12-18 2022-06-23 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating factor xii
JP2024500035A (ja) 2020-12-23 2024-01-04 アルゴノート アールエヌエー リミテッド 心血管疾患の治療
EP4273245A1 (en) 2020-12-29 2023-11-08 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition and sirna conjugate containing the nucleic acid, preparation method therefor, and use thereof
WO2022150260A1 (en) 2021-01-05 2022-07-14 Alnylam Pharmaceuticals, Inc. COMPLEMENT COMPONENT 9 (C9) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
AU2022215065A1 (en) * 2021-01-30 2023-07-27 E-Therapeutics Plc Conjugated oligonucleotide compounds, methods of making and uses thereof
CA3204340A1 (en) * 2021-01-30 2022-08-04 Ahmad Ali MORTAZAVI Conjugated oligonucleotide compounds, methods of making and uses thereof
WO2022162157A1 (en) * 2021-01-30 2022-08-04 E-Therapeutics Plc Conjugated oligonucleotide compounds, methods of making and uses thereof
WO2022162161A1 (en) * 2021-01-30 2022-08-04 E-Therapeutics Plc Conjugated oligonucleotide compounds, methods of making and uses thereof
TW202246500A (zh) 2021-02-02 2022-12-01 瑞士商赫孚孟拉羅股份公司 用於抑制 ｒｔｅｌ１ 表現之增強型寡核苷酸
KR20230146048A (ko) 2021-02-12 2023-10-18 알닐람 파마슈티칼스 인코포레이티드 슈퍼옥사이드 디스뮤타제 1(sod1) irna 조성물 및 슈퍼옥사이드 디스뮤타제 1- (sod1-) 관련 신경퇴행성 질환을 치료하거나 예방하기 위한 이의 사용 방법
WO2022175749A1 (en) * 2021-02-18 2022-08-25 Oneglobe Holdings Limited Compositions for conjugating oligonucleotides and carbohydrates
WO2022182864A1 (en) 2021-02-25 2022-09-01 Alnylam Pharmaceuticals, Inc. Prion protein (prnp) irna compositions and methods and methods of use thereof
EP4298218A1 (en) 2021-02-26 2024-01-03 Alnylam Pharmaceuticals, Inc. Ketohexokinase (khk) irna compositions and methods of use thereof
WO2022187435A1 (en) 2021-03-04 2022-09-09 Alnylam Pharmaceuticals, Inc. Angiopoietin-like 3 (angptl3) irna compositions and methods of use thereof
EP4305168A1 (en) 2021-03-08 2024-01-17 Les Laboratoires Servier Antisense oligonucleotides for inhibiting alpha-synuclein expression
WO2022189861A1 (en) 2021-03-08 2022-09-15 Tollys Carbohydrate conjugates of tlr3 ligands and uses thereof
EP4305169A1 (en) 2021-03-12 2024-01-17 Alnylam Pharmaceuticals, Inc. Glycogen synthase kinase 3 alpha (gsk3a) irna compositions and methods of use thereof
MX2023011466A (es) 2021-03-29 2024-02-01 Alnylam Pharmaceuticals Inc Composiciones de agentes de ácido ribonucleico de interferencia (arni) de huntingtina (htt) y métodos de uso de estas.
WO2022212153A1 (en) 2021-04-01 2022-10-06 Alnylam Pharmaceuticals, Inc. Proline dehydrogenase 2 (prodh2) irna compositions and methods of use thereof
KR20230171431A (ko) 2021-04-14 2023-12-20 다이서나 파마수이티컬, 인크. Pnpla3 발현을 조절하기 위한 조성물 및 방법
EP4330392A1 (en) 2021-04-26 2024-03-06 Alnylam Pharmaceuticals, Inc. Transmembrane protease, serine 6 (tmprss6) irna compositions and methods of use thereof
EP4330396A1 (en) 2021-04-29 2024-03-06 Alnylam Pharmaceuticals, Inc. Signal transducer and activator of transcription factor 6 (stat6) irna compositions and methods of use thereof
WO2022232650A1 (en) * 2021-04-30 2022-11-03 Ionis Pharmaceuticals, Inc. Methods for reducing agt expression
EP4341401A1 (en) 2021-05-18 2024-03-27 Alnylam Pharmaceuticals, Inc. Sodium-glucose cotransporter-2 (sglt2) irna compositions and methods of use thereof
US20240263177A1 (en) 2021-05-20 2024-08-08 Korro Bio, Inc. Methods and Compositions for Adar-Mediated Editing
WO2022256283A2 (en) 2021-06-01 2022-12-08 Korro Bio, Inc. Methods for restoring protein function using adar
TW202317762A (zh) 2021-06-02 2023-05-01 美商艾拉倫製藥股份有限公司 含有類ＰＡＴＡＴＩＮ磷脂酶結構域３（ＰＮＰＬＡ３）的ｉＲＮＡ組成物及其使用方法
KR20240017911A (ko) 2021-06-04 2024-02-08 알닐람 파마슈티칼스 인코포레이티드 인간 염색체 9 개방 해독 프레임 72(C9orf72) iRNA 제제 조성물 및 이의 사용 방법
EP4351541A2 (en) 2021-06-08 2024-04-17 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating or preventing stargardt's disease and/or retinal binding protein 4 (rbp4)-associated disorders
BR112023026050A2 (pt) 2021-06-18 2024-03-05 Ionis Pharmaceuticals Inc Compostos e métodos para reduzir expressão de ifnar1
BR112023026862A2 (pt) 2021-06-23 2024-03-05 Beth Israel Deaconess Medical Ct Inc Compostos de oligonucleotídeos anti-flt1 otimizados para tratamento de pré-eclâmpsia e outros distúrbios angiogênicos
JP2024523565A (ja) * 2021-06-24 2024-06-28 イーライ リリー アンド カンパニー 新規ｒｎａ治療法及びその使用
CN117858948A (zh) * 2021-06-24 2024-04-09 伊莱利利公司 新的治疗剂递送部分及其用途
US20230194709A9 (en) 2021-06-29 2023-06-22 Seagate Technology Llc Range information detection using coherent pulse sets with selected waveform characteristics
EP4363574A1 (en) 2021-06-29 2024-05-08 Korro Bio, Inc. Methods and compositions for adar-mediated editing
IL309296A (en) 2021-06-30 2024-02-01 Alnylam Pharmaceuticals Inc Methods and compositions for the treatment of angiotensinogen-related disorder (AGT-)
TW202317197A (zh) * 2021-07-02 2023-05-01 大陸商上海拓界生物醫藥科技有限公司 一種核酸配體及其綴合物、其製備方法和用途
TW202317147A (zh) 2021-07-08 2023-05-01 日商日本新藥股份有限公司 析出抑制劑
JPWO2023282344A1 (es) 2021-07-08 2023-01-12
EP4368186A1 (en) 2021-07-08 2024-05-15 Nippon Shinyaku Co., Ltd. Nephrotoxicity reducing agent
WO2023003805A1 (en) 2021-07-19 2023-01-26 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating subjects having or at risk of developing a non-primary hyperoxaluria disease or disorder
TW202325312A (zh) 2021-07-23 2023-07-01 美商艾拉倫製藥股份有限公司 β－鏈蛋白（ＣＴＮＮＢ１）ｉＲＮＡ組成物及其使用方法
EP4377458A1 (en) 2021-07-29 2024-06-05 Alnylam Pharmaceuticals, Inc. 3-hydroxy-3-methylglutaryl-coa reductase (hmgcr) irna compositions and methods of use thereof
EP4380576A2 (en) * 2021-08-03 2024-06-12 Verve Therapeutics, Inc. Compositions and methods for targeted rna delivery
CN117795074A (zh) 2021-08-03 2024-03-29 阿尔尼拉姆医药品有限公司 转甲状腺素蛋白（TTR）iRNA组合物和其使用方法
JP2024531914A (ja) 2021-08-04 2024-09-03 アルナイラム ファーマシューティカルズ， インコーポレイテッド アンジオテンシノーゲン（ａｇｔ）をサイレンシングするためのｉｒｎａ組成物および方法
AU2022328347A1 (en) 2021-08-13 2024-02-08 Alnylam Pharmaceuticals, Inc. Factor xii (f12) irna compositions and methods of use thereof
CA3229020A1 (en) 2021-09-14 2023-03-23 Stella Khan Treatment of cardiovascular disease
EP4401742A2 (en) 2021-09-17 2024-07-24 Alnylam Pharmaceuticals, Inc. Irna compositions and methods for silencing complement component 3 (c3)
AU2022348141A1 (en) * 2021-09-18 2024-04-04 Chengdu Xinzhenghe Pharmaceutical Technology Co. Ltd Lpa inhibitor and use thereof
CA3232420A1 (en) 2021-09-20 2023-03-23 Alnylam Pharmaceuticals, Inc. Inhibin subunit beta e (inhbe) modulator compositions and methods of use thereof
KR20240082358A (ko) * 2021-09-23 2024-06-10 상하이 아르고 바이오파마슈티칼 씨오., 엘티디. 치료제의 표적화된 전달을 위한 디아민 스캐폴드를 갖는 다가 리간드 클러스터
MX2024004011A (es) 2021-10-01 2024-07-01 Adarx Pharmaceuticals Inc Composiciones moduladoras de precalicreína y métodos de uso de estas.
AU2022370009A1 (en) 2021-10-22 2024-05-16 Korro Bio, Inc. Methods and compositions for disrupting nrf2-keap1 protein interaction by adar mediated rna editing
EP4423273A1 (en) 2021-10-29 2024-09-04 Alnylam Pharmaceuticals, Inc. Complement factor b (cfb) irna compositions and methods of use thereof
EP4423272A2 (en) 2021-10-29 2024-09-04 Alnylam Pharmaceuticals, Inc. Huntingtin (htt) irna agent compositions and methods of use thereof
IL312635A (en) 2021-11-11 2024-07-01 Hoffmann La Roche Pharmaceutical combinations for the treatment of HBV
CA3241316A1 (en) * 2021-12-03 2023-06-08 Quralis Corporation Gapmer antisense oligonucleotides with modified backbone chemistries
GB202117758D0 (en) 2021-12-09 2022-01-26 Ucl Business Ltd Therapeutics for the treatment of neurodegenerative disorders
WO2023109945A1 (zh) * 2021-12-16 2023-06-22 上海拓界生物医药科技有限公司 一种dsRNA、其制备方法及应用
CN118076738A (zh) * 2021-12-16 2024-05-24 上海拓界生物医药科技有限公司 靶向LPA的siRNA及缀合物
WO2023111210A1 (en) 2021-12-17 2023-06-22 F. Hoffmann-La Roche Ag Combination of oligonucleotides for modulating rtel1 and fubp1
WO2023138659A1 (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
TW202345865A (zh) * 2022-01-24 2023-12-01 大陸商上海舶望製藥有限公司 抑制LPA(Apo(a))蛋白表達的組合物和方法
WO2023141314A2 (en) 2022-01-24 2023-07-27 Alnylam Pharmaceuticals, Inc. Heparin sulfate biosynthesis pathway enzyme irna agent compositions and methods of use thereof
CN116917477B (zh) * 2022-01-30 2024-04-09 大睿生物医药科技(上海)有限公司 含有n-乙酰半乳糖胺的靶向配体
US20240167040A1 (en) 2022-02-21 2024-05-23 Hoffmann-La Roche Inc. Antisense oligonucleotide
CN114703184B (zh) * 2022-03-11 2024-06-18 厦门甘宝利生物医药有限公司 Lpa抑制剂及其用途
WO2023178144A2 (en) 2022-03-16 2023-09-21 Empirico Inc. Galnac compositions for improving sirna bioavailability
CN115028670B (zh) * 2022-06-24 2023-07-28 四川大学华西医院 一种n-乙酰基-d-半乳糖胺三聚体前体的制备方法
WO2024001172A1 (en) * 2022-06-27 2024-01-04 Ractigen Therapeutics Oligonucleotide modulators activating complement factor h expression
WO2024013360A1 (en) 2022-07-15 2024-01-18 Proqr Therapeutics Ii B.V. Chemically modified oligonucleotides for adar-mediated rna editing
WO2024013361A1 (en) 2022-07-15 2024-01-18 Proqr Therapeutics Ii B.V. Oligonucleotides for adar-mediated rna editing and use thereof
CN116814621A (zh) * 2022-08-05 2023-09-29 厦门甘宝利生物医药有限公司 一种抑制apoc3基因表达的rna抑制剂及其应用
WO2024039776A2 (en) 2022-08-18 2024-02-22 Alnylam Pharmaceuticals, Inc. Universal non-targeting sirna compositions and methods of use thereof
WO2024059165A1 (en) 2022-09-15 2024-03-21 Alnylam Pharmaceuticals, Inc. 17b-hydroxysteroid dehydrogenase type 13 (hsd17b13) irna compositions and methods of use thereof
WO2024098061A2 (en) 2022-11-04 2024-05-10 Genkardia Inc. Oligonucleotide-based therapeutics targeting cyclin d2 for the treatment of heart failure
WO2024108217A1 (en) 2022-11-18 2024-05-23 Genkardia Inc. Methods and compositions for preventing, treating, or reversing cardiac diastolic dysfunction
WO2024106539A1 (ja) * 2022-11-18 2024-05-23 株式会社ボナック リガンドコンジュゲート物質及びそれを含む核酸並びにその用途
WO2024112937A2 (en) * 2022-11-23 2024-05-30 Pretzel Therapeutics, Inc. Compositions and methods for treatment of cancer and metabolic disease
WO2024114776A1 (zh) * 2022-12-02 2024-06-06 上海舶望制药有限公司 双环脱碱基核酸类似物以及由它们制备的寡聚化合物
WO2024137729A1 (en) * 2022-12-21 2024-06-27 Eli Lilly And Company NOVEL FAS RNAi THERAPEUTICS AND USES THEREOF
WO2024149282A1 (en) * 2023-01-10 2024-07-18 Ausperbio Therapeutics Inc. Modified multi-segmented antisense oligonucleotides for use
WO2024168010A2 (en) 2023-02-09 2024-08-15 Alnylam Pharmaceuticals, Inc. Reversir molecules and methods of use thereof
WO2024175113A1 (zh) * 2023-02-24 2024-08-29 南京明德新药研发有限公司 包含R和E的双链siRNA类似物及其缀合物
CN116925160B (zh) * 2023-09-15 2023-12-08 天津全和诚科技有限责任公司 一种GalNAc含糖环中间体及其制备方法
CN117568313B (zh) * 2024-01-15 2024-04-26 上海贝斯昂科生物科技有限公司 基因编辑组合物及其用途
CN118146284B (zh) * 2024-05-08 2024-07-26 北京悦康科创医药科技股份有限公司 一种GalNAc化合物、其与寡核苷酸缀合物及制备方法

Family Cites Families (379)

* 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
US5132418A (en) 1980-02-29 1992-07-21 University Patents, Inc. Process for preparing polynucleotides
US4458066A (en) 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
US4500707A (en) 1980-02-29 1985-02-19 University Patents, Inc. Nucleosides useful in the preparation of polynucleotides
US4469863A (en) 1980-11-12 1984-09-04 Ts O Paul O P Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof
US4668777A (en) 1981-03-27 1987-05-26 University Patents, Inc. Phosphoramidite nucleoside compounds
US4415732A (en) 1981-03-27 1983-11-15 University Patents, Inc. Phosphoramidite compounds and processes
US4973679A (en) 1981-03-27 1990-11-27 University Patents, Inc. Process for oligonucleo tide synthesis using phosphormidite intermediates
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
US4476301A (en) 1982-04-29 1984-10-09 Centre National De La Recherche Scientifique Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon
DE3329892A1 (de) 1983-08-18 1985-03-07 Köster, Hubert, Prof. Dr., 2000 Hamburg Verfahren zur herstellung von oligonucleotiden
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
USRE34036E (en) 1984-06-06 1992-08-18 National Research Development Corporation Data transmission using a transparent tone-in band system
US5550111A (en) 1984-07-11 1996-08-27 Temple University-Of The Commonwealth System Of Higher Education Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof
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
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
FR2575751B1 (fr) 1985-01-08 1987-04-03 Pasteur Institut Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques
US4751219A (en) 1985-02-05 1988-06-14 Nederlandse Centrale Organisatie Voor Toegepast-Natuur-Wetenschappelijk Onderzoek Synthetic glycolipides, a process for the preparation thereof and several uses for these synthetic glycolipides
US5506337A (en) 1985-03-15 1996-04-09 Antivirals Inc. Morpholino-subunit combinatorial library and method
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
DE3788914T2 (de) 1986-09-08 1994-08-25 Ajinomoto Kk Verbindungen zur Spaltung von RNS an eine spezifische Position, Oligomere, verwendet bei der Herstellung dieser Verbindungen und Ausgangsprodukte für die Synthese dieser Oligomere.
US5276019A (en) 1987-03-25 1994-01-04 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US5264423A (en) 1987-03-25 1993-11-23 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
GB8712540D0 (en) * 1987-05-28 1987-07-01 Ucb Sa Expression of human proapolipoprotein a-i
WO1988010264A1 (en) 1987-06-24 1988-12-29 Howard Florey Institute Of Experimental Physiology Nucleoside derivatives
US4924624A (en) 1987-10-22 1990-05-15 Temple University-Of The Commonwealth System Of Higher Education 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
ATE151467T1 (de) 1987-11-30 1997-04-15 Univ Iowa Res Found Durch modifikationen an der 3'-terminalen phosphodiesterbindung stabilisierte dna moleküle, ihre verwendung als nukleinsäuresonden sowie als therapeutische mittel zur hemmung der expression spezifischer zielgene
US5403711A (en) 1987-11-30 1995-04-04 University Of Iowa Research Foundation Nucleic acid hybridization and amplification method for detection of specific sequences in which a complementary labeled nucleic acid probe is cleaved
WO1989009221A1 (en) 1988-03-25 1989-10-05 University Of Virginia Alumni Patents Foundation Oligonucleotide n-alkylphosphoramidates
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
US5194599A (en) 1988-09-23 1993-03-16 Gilead Sciences, Inc. Hydrogen phosphonodithioate compositions
US5256775A (en) 1989-06-05 1993-10-26 Gilead Sciences, Inc. Exonuclease-resistant oligonucleotides
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
US5721218A (en) 1989-10-23 1998-02-24 Gilead Sciences, Inc. Oligonucleotides with inverted polarity
EP0942000B1 (en) 1989-10-24 2004-06-23 Isis Pharmaceuticals, Inc. 2'-Modified oligonucleotides
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5130302A (en) 1989-12-20 1992-07-14 Boron Bilogicals, Inc. Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same
US5859221A (en) 1990-01-11 1999-01-12 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US5623065A (en) 1990-08-13 1997-04-22 Isis Pharmaceuticals, Inc. Gapped 2' modified oligonucleotides
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US6005087A (en) 1995-06-06 1999-12-21 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US7101993B1 (en) 1990-01-11 2006-09-05 Isis Pharmaceuticals, Inc. Oligonucleotides containing 2′-O-modified purines
US5457191A (en) 1990-01-11 1995-10-10 Isis Pharmaceuticals, Inc. 3-deazapurines
US5149797A (en) 1990-02-15 1992-09-22 The Worcester Foundation For Experimental Biology Method of site-specific alteration of rna and production of encoded polypeptides
US5220007A (en) 1990-02-15 1993-06-15 The Worcester Foundation For Experimental Biology Method of site-specific alteration of RNA and production of encoded polypeptides
US5321131A (en) 1990-03-08 1994-06-14 Hybridon, Inc. Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling
US5470967A (en) 1990-04-10 1995-11-28 The Dupont Merck Pharmaceutical Company Oligonucleotide analogs with sulfamate linkages
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.
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5223618A (en) 1990-08-13 1993-06-29 Isis Pharmaceuticals, Inc. 4'-desmethyl nucleoside analog compounds
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5614617A (en) 1990-07-27 1997-03-25 Isis Pharmaceuticals, Inc. Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5386023A (en) 1990-07-27 1995-01-31 Isis Pharmaceuticals Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling
US5378825A (en) 1990-07-27 1995-01-03 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
ES2083593T3 (es) 1990-08-03 1996-04-16 Sterling Winthrop Inc Compuestos y metodos para inhibir la expresion de genes.
US5177196A (en) 1990-08-16 1993-01-05 Microprobe Corporation Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof
US5214134A (en) 1990-09-12 1993-05-25 Sterling Winthrop Inc. Process of linking nucleosides with a siloxane bridge
US5561225A (en) 1990-09-19 1996-10-01 Southern Research Institute Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages
WO1992005186A1 (en) 1990-09-20 1992-04-02 Gilead Sciences Modified internucleoside linkages
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
US6582908B2 (en) 1990-12-06 2003-06-24 Affymetrix, Inc. Oligonucleotides
US5948903A (en) 1991-01-11 1999-09-07 Isis Pharmaceuticals, Inc. Synthesis of 3-deazapurines
US5672697A (en) 1991-02-08 1997-09-30 Gilead Sciences, Inc. Nucleoside 5'-methylene phosphonates
US7015315B1 (en) 1991-12-24 2006-03-21 Isis Pharmaceuticals, Inc. Gapped oligonucleotides
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
ES2103918T3 (es) 1991-10-17 1997-10-01 Ciba Geigy Ag Nucleosidos biciclicos, oligonucleotidos, procedimiento para su obtencion y productos intermedios.
US5594121A (en) 1991-11-07 1997-01-14 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified purines
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
JP3739785B2 (ja) 1991-11-26 2006-01-25 アイシス ファーマシューティカルズ，インコーポレイティド 修飾されたピリミジンを含有するオリゴマーを使用する増強された三重らせんおよび二重らせんの成形
TW393513B (en) 1991-11-26 2000-06-11 Isis Pharmaceuticals Inc Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines
US5792608A (en) 1991-12-12 1998-08-11 Gilead Sciences, Inc. Nuclease stable and binding competent oligomers and methods for their use
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
US5700922A (en) 1991-12-24 1997-12-23 Isis Pharmaceuticals, Inc. PNA-DNA-PNA chimeric macromolecules
AU669353B2 (en) * 1991-12-24 1996-06-06 Isis Pharmaceuticals, Inc. Gapped 2' modified oligonucleotides
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
US5633360A (en) 1992-04-14 1997-05-27 Gilead Sciences, Inc. Oligonucleotide analogs capable of passive cell membrane permeation
US5434257A (en) 1992-06-01 1995-07-18 Gilead Sciences, Inc. Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
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
US5652355A (en) 1992-07-23 1997-07-29 Worcester Foundation For Experimental Biology Hybrid oligonucleotide phosphorothioates
RU95104940A (ru) 1992-07-27 1997-01-10 Хайбрайдон Способ введения в олигонуклеотид алкилфосфонотиоатной или арилфосфонотиоатной межнуклеотидной связи, способ получения олигонуклеотида, олигонуклеотиды, способ ингибирования генной экспрессии, способ лечения
JPH08504559A (ja) 1992-12-14 1996-05-14 ハネウエル・インコーポレーテッド 個別に制御される冗長巻線を有するモータシステム
JPH08508714A (ja) 1993-01-25 1996-09-17 ハイブライドン インコーポレイテッド オリゴヌクレオチド・アルキルホスホネートおよびアルキルホスホノチオエート
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
GB9304620D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Compounds
DK0691968T3 (da) 1993-03-30 1998-02-23 Sanofi Sa Acykliske nukleosid-analoge og oligonukleotidsekvenser indeholdende disse
AU6412794A (en) 1993-03-31 1994-10-24 Sterling Winthrop Inc. Oligonucleotides with amide linkages replacing phosphodiester linkages
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
US5801154A (en) 1993-10-18 1998-09-01 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of multidrug resistance-associated protein
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
PT733059E (pt) 1993-12-09 2001-03-30 Univ Jefferson Compostos e metodos para mutacoes dirigidas ao local em celulas eucarioticas
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
US5728518A (en) 1994-01-12 1998-03-17 The Immune Response Corporation Antiviral poly-and oligonucleotides
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
US5625050A (en) 1994-03-31 1997-04-29 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
US5646269A (en) 1994-04-28 1997-07-08 Gilead Sciences, Inc. Method for oligonucleotide analog synthesis
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
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
US5599706A (en) 1994-09-23 1997-02-04 Stinchcomb; Dan T. Ribozymes targeted to apo(a) mRNA
US5681940A (en) 1994-11-02 1997-10-28 Icn Pharmaceuticals Sugar modified nucleosides and oligonucleotides
US6172045B1 (en) 1994-12-07 2001-01-09 Neorx Corporation Cluster clearing agents
US6908903B1 (en) 1994-12-07 2005-06-21 Aletheon Pharmaceuticals, Inc. Cluster clearing agents
US5652356A (en) 1995-08-17 1997-07-29 Hybridon, Inc. Inverted chimeric and hybrid oligonucleotides
US20030119724A1 (en) 1995-11-22 2003-06-26 Ts`O Paul O.P. Ligands to enhance cellular uptake of biomolecules
AU1039397A (en) 1995-11-22 1997-06-27 Johns Hopkins University, The Ligands to enhance cellular uptake of biomolecules
US5998203A (en) 1996-04-16 1999-12-07 Ribozyme Pharmaceuticals, Inc. Enzymatic nucleic acids containing 5'-and/or 3'-cap structures
WO2005121370A2 (en) 2004-06-03 2005-12-22 Isis Pharmaceuticals, Inc. Oligomeric compounds that facilitate risc loading
WO1998013381A1 (fr) 1996-09-26 1998-04-02 Ajinomoto Co., Inc. Proteines modifiees physiologiquement actives et compositions medicamenteuses les contenant
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
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
USRE44779E1 (en) 1997-03-07 2014-02-25 Santaris Pharma A/S Bicyclonucleoside and oligonucleotide analogues
EP1557424A1 (en) 1997-09-12 2005-07-27 Exiqon A/S Bi-cyclic nucleoside, nucleotide and oligonucleoide analogues
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
US20040171564A1 (en) 1997-11-20 2004-09-02 Honkanen Richard E. Antisense oligonucleotide modulation of human serine/threonine protein phosphatase gene expression
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
NZ509986A (en) 1998-08-19 2003-10-31 Baxter Healthcare S Immunogenic beta-propionamido-linked polysaccharide and oligosaccharide protein conjugates as vaccines
PL346645A1 (en) * 1998-08-19 2002-02-25 North American Vaccine IMMUNOGENIC β-PROPIONAMIDO-LINKED POLYSACCHARIDE PROTEIN CONJUGATE USEFUL AS A VACCINE PRODUCED USING AN N-ACRYLOYLATED POLYSACCHARIDE
US6166239A (en) 1998-09-04 2000-12-26 Isis Pharmaceuticals, Inc. Oligonucleotide protecting groups
ID30093A (id) 1999-02-12 2001-11-01 Sankyo Co Analog-analog nukleosida dan oligonukleotida baru
US20030170249A1 (en) 1999-02-19 2003-09-11 Hakomori Sen-Itiroh Vaccines directed to cancer-associated carbohydrate antigens
US7084125B2 (en) 1999-03-18 2006-08-01 Exiqon A/S Xylo-LNA analogues
US6159694A (en) 1999-04-08 2000-12-12 Isis Pharmaceuticals Inc. Antisense modulation of stat3 expression
US7098192B2 (en) * 1999-04-08 2006-08-29 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of STAT3 expression
WO2000063364A2 (en) 1999-04-21 2000-10-26 American Home Products Corporation Methods and compositions for inhibiting the function of polynucleotide sequences
ES2283298T3 (es) 1999-05-04 2007-11-01 Santaris Pharma A/S Analogos de l-ribo-lna.
US6525191B1 (en) 1999-05-11 2003-02-25 Kanda S. Ramasamy Conformationally constrained L-nucleosides
US6383812B1 (en) 1999-05-28 2002-05-07 Academia Sinica Anti liver disease drug R-YEEE and method of synthesizing branched galactose-terminal glycoproteins
US8541548B2 (en) 1999-06-07 2013-09-24 Arrowhead Madison Inc. Compounds and methods for reversible modification of biologically active molecules
US20080281041A1 (en) 1999-06-07 2008-11-13 Rozema David B Reversibly Masked Polymers
US6656730B1 (en) 1999-06-15 2003-12-02 Isis Pharmaceuticals, Inc. Oligonucleotides conjugated to protein-binding drugs
AU6605900A (en) 1999-07-16 2001-02-05 Hyseq, Inc. Novel angiopoietin materials and methods
JP4151751B2 (ja) 1999-07-22 2008-09-17 第一三共株式会社 新規ビシクロヌクレオシド類縁体
DE19935303A1 (de) * 1999-07-28 2001-02-08 Aventis Pharma Gmbh Oligonukleotide zur Inhibierung der Expression von humanem eg5
US20020082227A1 (en) 1999-09-30 2002-06-27 Scott Henry Use of oligonucleotides for inhibition of complement activation
US20050112118A1 (en) 1999-12-02 2005-05-26 Myriad Genetics, Incorporated Compositions and methods for treating inflammatory disorders
WO2001042499A1 (fr) 1999-12-09 2001-06-14 Sankyo Company, Limited Procede d'essai d'agent curatif ou preventif de l'hyperlipemie
AU2698301A (en) 1999-12-30 2001-07-16 K.U. Leuven Research And Development Cyclohexene nucleic acids
US7179796B2 (en) 2000-01-18 2007-02-20 Isis Pharmaceuticals, Inc. Antisense modulation of PTP1B expression
US6602857B1 (en) 2000-01-18 2003-08-05 Isis Pharmaceuticals, Inc. Antisense modulation of PTP1B expression
US6261840B1 (en) 2000-01-18 2001-07-17 Isis Pharmaceuticals, Inc. Antisense modulation of PTP1B expression
US20020055479A1 (en) 2000-01-18 2002-05-09 Cowsert Lex M. Antisense modulation of PTP1B expression
US7491805B2 (en) 2001-05-18 2009-02-17 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US7833992B2 (en) 2001-05-18 2010-11-16 Merck Sharpe & Dohme Conjugates and compositions for cellular delivery
US8202979B2 (en) 2002-02-20 2012-06-19 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid
WO2001060860A2 (en) 2000-02-17 2001-08-23 Millennium Predictive Medicine, Inc. Genes differentially expressed in human prostate cancer and their use
US7053199B2 (en) 2000-08-29 2006-05-30 Takeshi Imanishi Nucleoside analogs and oligonucleotide derivatives containing these analogs
US6426220B1 (en) 2000-10-30 2002-07-30 Isis Pharmaceuticals, Inc. Antisense modulation of calreticulin expression
AU2002217980A1 (en) 2000-12-01 2002-06-11 Cell Works Inc. Conjugates of glycosylated/galactosylated peptide
WO2002087541A1 (en) 2001-04-30 2002-11-07 Protiva Biotherapeutics Inc. Lipid-based formulations for gene transfer
IL159153A0 (en) 2001-06-08 2004-06-01 Sankyo Co Methods for testing drugs for treating or preventing diseases such as hyperlipidemia
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
US20030158403A1 (en) 2001-07-03 2003-08-21 Isis Pharmaceuticals, Inc. Nuclease resistant chimeric oligonucleotides
US20030175906A1 (en) 2001-07-03 2003-09-18 Muthiah Manoharan Nuclease resistant chimeric oligonucleotides
US7425545B2 (en) 2001-07-25 2008-09-16 Isis Pharmaceuticals, Inc. Modulation of C-reactive protein expression
US6964950B2 (en) 2001-07-25 2005-11-15 Isis Pharmaceuticals, Inc. Antisense modulation of C-reactive protein expression
US7259150B2 (en) 2001-08-07 2007-08-21 Isis Pharmaceuticals, Inc. Modulation of apolipoprotein (a) expression
US7227014B2 (en) * 2001-08-07 2007-06-05 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein (a) expression
WO2003014397A1 (en) 2001-08-09 2003-02-20 Biomedlab Corporation Probe for detection of enteric virus detection kit and method for enteric virus with the same
US7060809B2 (en) 2001-09-04 2006-06-13 Exiqon A/S LNA compositions and uses thereof
US7439043B2 (en) 2001-10-10 2008-10-21 Neose Technologies, Inc. Galactosyl nucleotide sugars
NZ532852A (en) 2001-11-16 2006-08-31 Genentech Inc Composition comprising and method of using angiopoietin-like protein 3 Angptl3
US20100240730A1 (en) 2002-02-20 2010-09-23 Merck Sharp And Dohme Corp. RNA Interference Mediated Inhibition of Gene Expression Using Chemically Modified Short Interfering Nucleic Acid (siNA)
EP1540004A4 (en) 2002-07-31 2007-10-03 Nucleonics Inc DOUBLE-STRING RNA STRUCTURES AND CONSTRUCTS AND METHOD FOR THE PRODUCTION AND USE THEREOF
WO2004014933A1 (en) 2002-08-07 2004-02-19 University Of Massachusetts Compositions for rna interference and methods of use thereof
WO2004024757A2 (en) 2002-09-11 2004-03-25 Santaris Pharma A/S Modified pna molecules
AU2003284323A1 (en) 2002-10-18 2004-05-04 Alnylam Pharmaceuticals Inc Double-stranded rna structures and constructs, and methods for generating and using the same
AU2003287502B2 (en) 2002-11-05 2010-12-09 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2'-modified nucleosides for use in gene modulation
AU2003291753B2 (en) 2002-11-05 2010-07-08 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
CA2505801A1 (en) 2002-11-13 2004-05-27 Rosanne Crooke Antisense modulation of apolipoprotein b expression
US20060009410A1 (en) 2002-11-13 2006-01-12 Crooke Rosanne M Effects of apolipoprotein B inhibition on gene expression profiles in animals
US7511131B2 (en) 2002-11-13 2009-03-31 Genzyme Corporation Antisense modulation of apolipoprotein B expression
DK2284266T3 (da) 2002-11-14 2014-01-13 Thermo Fisher Scient Biosciences Inc sIRNA-MOLEKYLE MOD TP53
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
EP2500440B1 (en) 2002-12-20 2015-12-16 Celera Corporation Genetic polymorphisms associated with myocardial infarction, methods of detection and uses thereof
US20070015927A1 (en) 2003-01-09 2007-01-18 Kim Byeang H New phosphoramidite compounds
WO2004072046A2 (en) 2003-02-12 2004-08-26 Carex S.A. Quinoline derivatives and their use for modulation of lxr activity
US7803781B2 (en) 2003-02-28 2010-09-28 Isis Pharmaceuticals, Inc. Modulation of growth hormone receptor expression and insulin-like growth factor expression
CA2518475C (en) 2003-03-07 2014-12-23 Alnylam Pharmaceuticals, Inc. Irna agents comprising asymmetrical modifications
AU2004227414A1 (en) * 2003-04-03 2004-10-21 Alnylam Pharmaceuticals iRNA conjugates
US7598227B2 (en) 2003-04-16 2009-10-06 Isis Pharmaceuticals Inc. Modulation of apolipoprotein C-III expression
JP4597976B2 (ja) 2003-04-17 2010-12-15 アルナイラム ファーマシューティカルズ インコーポレイテッド 修飾ｉＲＮＡ剤
US7723509B2 (en) 2003-04-17 2010-05-25 Alnylam Pharmaceuticals IRNA agents with biocleavable tethers
US7851615B2 (en) 2003-04-17 2010-12-14 Alnylam Pharmaceuticals, Inc. Lipophilic conjugated iRNA agents
US7750142B2 (en) 2003-04-28 2010-07-06 Isis Pharmaceuticals, Inc. Modulation of glucagon receptor expression
US7399853B2 (en) 2003-04-28 2008-07-15 Isis Pharmaceuticals Modulation of glucagon receptor expression
JPWO2004101619A1 (ja) 2003-05-15 2006-10-26 塩野義製薬株式会社 機能的糖ペプチドの合理的設計および合成
WO2004106356A1 (en) 2003-05-27 2004-12-09 Syddansk Universitet Functionalized nucleotide derivatives
ATE555118T1 (de) 2003-08-28 2012-05-15 Takeshi Imanishi Neue synthetische nukleidsäuren vom typ mit quervernetzter n-o-bindung
JP5379347B2 (ja) 2003-09-18 2013-12-25 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 ４’−チオヌクレオシドおよびオリゴマー化合物
EP2256200A3 (en) 2003-09-18 2012-07-18 Isis Pharmaceuticals, Inc. Modulation of eIF4E expression
US8258105B2 (en) * 2003-10-07 2012-09-04 Isis Pharmaceuticals, Inc. Antisense oligonucleotides optimized for kidney targeting
US7959919B2 (en) 2003-11-19 2011-06-14 Novelmed Therapeutics, Inc. Method of inhibiting factor B-mediated complement activation
WO2005065686A1 (en) 2004-01-07 2005-07-21 Adipogen Pharmaceuticals Pty Limited Differentiation modulating agents and uses therefor
US20050164271A1 (en) 2004-01-20 2005-07-28 Sanjay Bhanot Modulation of glucocorticoid receptor expression
WO2005075453A1 (ja) * 2004-02-05 2005-08-18 Japan Science And Technology Agency リンカー化合物及びリガンド複合体、並びにそれらの製造方法
US20050244869A1 (en) 2004-04-05 2005-11-03 Brown-Driver Vickie L Modulation of transthyretin expression
JPWO2005097155A1 (ja) 2004-04-08 2008-02-28 タカラバイオ株式会社 神経突起伸長誘導剤
JPWO2005116204A1 (ja) 2004-05-11 2008-06-19 株式会社アルファジェン Ｒｎａ干渉を生じさせるポリヌクレオチド、および、これを用いた遺伝子発現抑制方法
RU2380411C2 (ru) 2004-07-20 2010-01-27 Дженентек, Инк. Способ ингибирования пролиферации гепатоцитов, способ ингибирования клеточной адгезии гепатоцитов и способ ингибирования биологической активности angptl4 в гепатоцитах или предшественниках гепатоцитов
JP4947717B2 (ja) 2004-07-20 2012-06-06 ジェネンテック， インコーポレイテッド アンジオポエチン様４タンパク質のインヒビター、組み合わせ、およびそれらの使用
JP5192234B2 (ja) 2004-08-10 2013-05-08 アルナイラム ファーマシューティカルズ， インコーポレイテッド 化学修飾オリゴヌクレオチド
EP2409713B1 (en) 2004-08-10 2015-07-22 Genzyme Corporation Oligonucleotides for use in modulating lipoprotein and cholesterol levels in humans
WO2006031461A2 (en) 2004-09-09 2006-03-23 Isis Pharmaceuticals, Inc. Pyrrolidinyl groups for attaching conjugates to oligomeric compounds
CA2582464A1 (en) 2004-10-13 2006-04-27 Sanjay Bhanot Antisense modulation of ptp1b expression
EP1812569A2 (en) 2004-11-08 2007-08-01 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
WO2006078217A1 (en) 2005-01-24 2006-07-27 Avaris Ab COMPLEX CONTAINING SiRNA, ShRNA OR ANTISENSE MOLECULE AND FUNCTIONAL ENTITY, FOR IMPROVED SPECIFICITY AND DELIVERY
KR20080068019A (ko) * 2005-09-15 2008-07-22 산타리스 팔마 에이/에스 아포지단백질-ｂ100 발현 억제용 ｒｎａ 길항제 화합물
EP1941040A1 (en) 2005-09-19 2008-07-09 Johnson & Johnson Pharmaceutical Research & Development L.L.C. Modulation of glucocorticoid receptor expression
EA200800869A1 (ru) 2005-09-19 2008-10-30 ДЖОНСОН ЭНД ДЖОНСОН ФАРМАСЬЮТИКАЛ РИСЕРЧ ЭНД ДИВЕЛОПМЕНТ, Эл. Эл. Си. Модуляция экспрессии рецептора глюкагона
EP2428227B1 (en) * 2006-01-26 2016-06-22 Ionis Pharmaceuticals, Inc. Compositions and their uses directed to Huntingtin
US7569686B1 (en) 2006-01-27 2009-08-04 Isis Pharmaceuticals, Inc. Compounds and methods for synthesis of bicyclic nucleic acid analogs
AU2007211080B9 (en) 2006-01-27 2012-05-03 Isis Pharmaceuticals, Inc. 6-modified bicyclic nucleic acid analogs
AU2007257094B2 (en) 2006-05-05 2012-10-25 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of SGLT2
CN101553236A (zh) * 2006-05-05 2009-10-07 埃西斯药品公司 调节gccr的表达的化合物和方法
US7666854B2 (en) 2006-05-11 2010-02-23 Isis Pharmaceuticals, Inc. Bis-modified bicyclic nucleic acid analogs
US7547684B2 (en) 2006-05-11 2009-06-16 Isis Pharmaceuticals, Inc. 5′-modified bicyclic nucleic acid analogs
US8101585B2 (en) 2006-08-04 2012-01-24 Isis Pharmaceuticals, Inc. Compositions and methods for the modulation of JNK proteins
CN102614528B (zh) 2006-08-18 2014-02-26 箭头研究公司 用于体内递送多核苷酸的多缀合物
US8658211B2 (en) 2006-08-18 2014-02-25 Arrowhead Madison Inc. Polyconjugates for in vivo delivery of polynucleotides
JP5352462B2 (ja) 2006-09-22 2013-11-27 ダーマコン， インコーポレイテッド 二本鎖オリゴヌクレオチド複合体、ｒｎａ干渉による遺伝子サイレンシング方法、および医薬品組成物
DK2092065T4 (da) 2006-10-18 2019-10-21 Ionis Pharmaceuticals Inc Antisense-forbindelser
US8093222B2 (en) 2006-11-27 2012-01-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
MX2009005527A (es) 2006-11-27 2009-06-08 Isis Pharmaceuticals Inc Metodos para el tratamiento de hipercolesterolemia.
HUE033960T2 (en) 2006-12-08 2018-01-29 Lexicon Pharmaceuticals Inc Monoclonal Antibodies to ANGPTL3
CA2839162A1 (en) * 2006-12-20 2008-06-26 Xoma Technology Ltd. Methods for the treatment of il-1-.beta. related diseases
US20100190837A1 (en) 2007-02-15 2010-07-29 Isis Pharmaceuticals, Inc. 5'-Substituted-2-F' Modified Nucleosides and Oligomeric Compounds Prepared Therefrom
EP2604283A1 (en) 2007-02-16 2013-06-19 KTB Tumorforschungsgesellschaft mbH Receptor And Antigen Targeted Prodrug
CA2678774A1 (en) 2007-03-01 2008-09-04 Advanced Vision Therapies, Inc. Treatment of diseases characterized by inflammation
EP2126085A2 (en) 2007-03-02 2009-12-02 MDRNA, Inc. Nucleic acid compounds for inhibiting myc gene expression and uses thereof
AU2008242583B2 (en) 2007-04-23 2013-10-10 Alnylam Pharmaceuticals, Inc. Glycoconjugates of RNA interference agents
CA2688321A1 (en) 2007-05-30 2008-12-11 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
US20090004140A1 (en) 2007-06-26 2009-01-01 Yao-Ling Qiu 4-substituted pyrrolidine as anti-infectives
ES2376507T5 (es) 2007-07-05 2015-08-31 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos 6-disustituidos
AU2008286771B2 (en) 2007-08-15 2013-08-15 Isis Pharmaceuticals, Inc. Tetrahydropyran nucleic acid analogs
EP2192924B1 (en) * 2007-08-20 2017-10-11 Protalix Ltd. Saccharide-containing protein conjugates and uses thereof
NZ584827A (en) 2007-10-01 2012-10-26 Isis Pharmaceuticals Inc Antisense modulation of fibroblast growth factor receptor 4 expression
JP2011502514A (ja) 2007-11-09 2011-01-27 アイシス ファーマシューティカルズ インコーポレイティッド 第７因子発現の調節
US8546556B2 (en) 2007-11-21 2013-10-01 Isis Pharmaceuticals, Inc Carbocyclic alpha-L-bicyclic nucleic acid analogs
EP4074344A1 (en) 2007-12-04 2022-10-19 Arbutus Biopharma Corporation Targeting lipids
SG10202001748VA (en) 2007-12-27 2020-04-29 Stelic Institute Of Regenerative Medicine Stelic Institute & Co Sugar chain-related gene and use thereof
BRPI0907008A2 (pt) 2008-01-31 2015-07-07 Alnylam Pharmaceuticals Inc Métodos otimizados para liberação de dsrna alvejando o gene pcsk9
WO2009100320A2 (en) 2008-02-07 2009-08-13 Isis Pharmaceuticals, Inc. Bicyclic cyclohexitol nucleic acid analogs
US20110269814A1 (en) 2008-03-26 2011-11-03 Alnylam Pharamaceuticals, Inc. 2'-f modified rna interference agents
EP3604533A1 (en) 2008-04-11 2020-02-05 Arbutus Biopharma Corporation Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
WO2009143369A2 (en) 2008-05-22 2009-11-26 Isis Pharmaceuticals, Inc. Method of preparing nucleosides and analogs thereof without using chromatography
WO2009148605A2 (en) 2008-06-04 2009-12-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
EP2733222A1 (en) 2008-07-09 2014-05-21 Celera Corporation Genetic polymorphisms associated with cardiovascular diseases, methods of detection and uses thereof
EP2323667A4 (en) * 2008-08-07 2012-07-25 Isis Pharmaceuticals Inc MODULATION OF TRANSTHYRETIN EXPRESSION BY TREATMENT OF CNS DISEASES
EP3587434A1 (en) 2008-09-23 2020-01-01 Alnylam Pharmaceuticals Inc. Chemical modifications of monomers and oligonucleotides with click components for conjugation with ligands
EP2356129B1 (en) 2008-09-24 2013-04-03 Isis Pharmaceuticals, Inc. Substituted alpha-l-bicyclic nucleosides
DK2361256T3 (da) 2008-09-24 2013-07-01 Isis Pharmaceuticals Inc Cyclohexenyl-nukleinsyreanaloger
EP3335715A3 (en) 2008-10-15 2018-08-08 Ionis Pharmaceuticals, Inc. Modulation of factor 11 expression
CN103937793B (zh) * 2008-10-20 2017-08-11 阿尔尼拉姆医药品有限公司 抑制运甲状腺素蛋白表达的组合物和方法
US20120059045A1 (en) 2008-10-24 2012-03-08 Isis Pharmaceuticals, Inc. Methods of using oligomeric compounds comprising 2'-substituted nucleosides
WO2010048585A2 (en) 2008-10-24 2010-04-29 Isis Pharmaceuticals, Inc. Oligomeric compounds and methods
EP3808177A1 (en) 2008-11-10 2021-04-21 Arbutus Biopharma Corporation Novel lipids and compositions for the delivery of therapeutics
US9023820B2 (en) 2009-01-26 2015-05-05 Protiva Biotherapeutics, Inc. Compositions and methods for silencing apolipoprotein C-III expression
CA3036963A1 (en) 2009-01-29 2010-08-05 Arbutus Biopharma Corporation Lipid formulations comprising cationic lipid and a targeting lipid comprising n-acetyl galactosamine for delivery of nucleic acid
CA2753975C (en) 2009-03-02 2017-09-26 Alnylam Pharmaceuticals, Inc. Nucleic acid chemical modifications
FR2943060B1 (fr) 2009-03-13 2013-01-04 Commissariat Energie Atomique Agents chelatants d'ions metalliques, leurs procedes de preparation et leurs applications
EP2419146A4 (en) 2009-04-15 2013-11-27 Isis Pharmaceuticals Inc MODULATION OF INFLAMMATORY RESPONSES BY FACTOR XI
EP2416760A4 (en) 2009-05-05 2014-01-22 Tekmira Pharmaceuticals Corp LIPID COMPOSITIONS
US9200276B2 (en) 2009-06-01 2015-12-01 Halo-Bio Rnai Therapeutics, Inc. Polynucleotides for multivalent RNA interference, compositions and methods of use thereof
PL3431076T3 (pl) 2009-06-10 2022-01-31 Arbutus Biopharma Corporation Ulepszona formulacja lipidowa
KR20120050429A (ko) 2009-06-15 2012-05-18 알닐람 파마슈티칼스 인코포레이티드 Ｐｃｓｋ9 유전자를 표적으로 하는 지질 제형된 ｄｓｒｎａ
BR112012000421A2 (pt) 2009-07-06 2019-09-24 Alnylam Pharmaceuticals Inc composições e métodos para intensificar a produção de um produto biológico.
US8927513B2 (en) 2009-07-07 2015-01-06 Alnylam Pharmaceuticals, Inc. 5′ phosphate mimics
WO2011005861A1 (en) 2009-07-07 2011-01-13 Alnylam Pharmaceuticals, Inc. Oligonucleotide end caps
US20120214862A1 (en) 2009-07-16 2012-08-23 Isis Pharmaceuticals, Inc. Modulation of factor 7 expression
WO2011017521A2 (en) 2009-08-06 2011-02-10 Isis Pharmaceuticals, Inc. Bicyclic cyclohexose nucleic acid analogs
US8901072B2 (en) * 2009-08-12 2014-12-02 The Medicines Company Glycopeptide and lipoglycopeptide antibiotics with improved solubility
WO2011038356A2 (en) 2009-09-25 2011-03-31 Johns Hopkins University Novel liver-targeting agents and their synthesis
WO2011047312A1 (en) 2009-10-16 2011-04-21 Glaxo Group Limited Hbv antisense inhibitors
TWI391144B (zh) 2009-10-26 2013-04-01 Iner Aec Executive Yuan 一種定量肝殘餘功能的檢驗方法與其新穎肝受體造影檢驗藥劑
TWI388338B (zh) 2009-10-26 2013-03-11 Iner Aec Executive Yuan 對聚合醣鏈進行放射標誌以作為肝受體造影劑之方法
EP2496238A4 (en) * 2009-11-03 2013-10-02 Alnylam Pharmaceuticals Inc FORMULATED LIPID COMPOSITIONS AND METHODS FOR INHIBITING TRANSTHYRETIN EXPRESSION (TTR)
WO2011072290A2 (en) 2009-12-11 2011-06-16 The Regents Of The University Of Michigan Targeted dendrimer-drug conjugates
WO2011085271A2 (en) 2010-01-08 2011-07-14 Isis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
WO2011100131A2 (en) 2010-01-28 2011-08-18 Alnylam Pharmacuticals, Inc. Monomers and oligonucleotides comprising cycloaddition adduct(s)
DK2539451T3 (da) * 2010-02-24 2016-04-04 Arrowhead Res Corp Sammensætninger til målrettet tilførsel af siRNA
WO2011115818A1 (en) 2010-03-17 2011-09-22 Isis Pharmaceuticals, Inc. 5'-substituted bicyclic nucleosides and oligomeric compounds prepared therefrom
JP2013528665A (ja) 2010-03-26 2013-07-11 メルサナ セラピューティックス， インコーポレイテッド ポリヌクレオチドの送達のための修飾ポリマー、その製造方法、およびその使用方法
US20130109817A1 (en) 2010-03-26 2013-05-02 Mersana Therapeutics, Inc. Modified Polymers for Delivery of Polynucleotides, Method of Manufacture, and Methods of Use Thereof
US9102938B2 (en) 2010-04-01 2015-08-11 Alnylam Pharmaceuticals, Inc. 2′ and 5′ modified monomers and oligonucleotides
US10913767B2 (en) 2010-04-22 2021-02-09 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising acyclic and abasic nucleosides and analogs
WO2011133871A2 (en) 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. 5'-end derivatives
US9127033B2 (en) 2010-04-28 2015-09-08 Isis Pharmaceuticals, Inc. 5′ modified nucleosides and oligomeric compounds prepared therefrom
US8993738B2 (en) 2010-04-28 2015-03-31 Isis Pharmaceuticals, Inc. Modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom
PT2563920T (pt) * 2010-04-29 2017-05-26 Ionis Pharmaceuticals Inc Modulação da expressão de transtirretina
US20130236968A1 (en) 2010-06-21 2013-09-12 Alnylam Pharmaceuticals, Inc. Multifunctional copolymers for nucleic acid delivery
EP2616543A1 (en) * 2010-09-15 2013-07-24 Alnylam Pharmaceuticals, Inc. MODIFIED iRNA AGENTS
WO2012067970A2 (en) 2010-11-11 2012-05-24 Ted M Dawson Transcriptional repression leading to parkinson's disease
WO2012068187A1 (en) 2010-11-19 2012-05-24 Merck Sharp & Dohme Corp. Poly(amide) polymers for the delivery of oligonucleotides
JP2014504295A (ja) 2010-12-17 2014-02-20 アローヘッド リサーチ コーポレイション ｓｉＲＮＡ用ガラクトースクラスター−薬物動態調節剤標的指向部分
US8501930B2 (en) 2010-12-17 2013-08-06 Arrowhead Madison Inc. Peptide-based in vivo siRNA delivery system
EP2658981B1 (en) 2010-12-29 2016-09-28 F.Hoffmann-La Roche Ag Small molecule conjugates for intracellular delivery of nucleic acids
EP3067421B1 (en) 2011-02-08 2018-10-10 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
CN107012144A (zh) 2011-04-01 2017-08-04 Ionis制药公司 信号转导及转录激活蛋白3(stat3)表达的调节
JP5951752B2 (ja) * 2011-04-13 2016-07-13 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． Ｐｔｐ１ｂ発現のアンチセンス調節
TW201303013A (zh) 2011-04-21 2013-01-16 Isis Pharmaceuticals Inc Ｂ型肝炎病毒（ｈｂｖ）表現之調節
SI3505528T1 (sl) 2011-04-21 2021-04-30 Glaxo Group Limited Modulacija izražanja virusa hepatitisa B (HBV)
KR20190062511A (ko) 2011-04-27 2019-06-05 아이오니스 파마수티컬즈, 인코포레이티드 아포지방단백질 ｃｉｉｉ （ａｐｏｃｉｉｉ） 발현의 조정
WO2012174154A1 (en) 2011-06-13 2012-12-20 Isis Pharmaceuticals, Inc. Modulation of inflammatory responses by factor vii
EP2721156B1 (en) 2011-06-16 2016-12-21 Ionis Pharmaceuticals, Inc. Antisense modulation of fibroblast growth factor receptor 4 expression
KR102540778B1 (ko) 2011-06-21 2023-06-07 알닐람 파마슈티칼스 인코포레이티드 아포리포단백질 c-iii(apoc3) 유전자의 발현 억제를 위한 조성물 및 방법
EP2723758B1 (en) * 2011-06-21 2018-06-20 Alnylam Pharmaceuticals, Inc. Angiopoietin-like 3 (angptl3) irna compostions and methods of use thereof
WO2012177639A2 (en) 2011-06-22 2012-12-27 Alnylam Pharmaceuticals, Inc. Bioprocessing and bioproduction using avian cell lines
US20130017250A1 (en) * 2011-07-15 2013-01-17 The Trustees Of Columbia University In The City Of New York Methods For High Density Lipoprotein Cholesterol Regulation
US8932572B2 (en) 2011-08-26 2015-01-13 Arrowhead Madison Inc. Poly(vinyl ester) polymers for in vivo nucleic acid delivery
DK2751270T3 (en) 2011-08-29 2018-10-29 Ionis Pharmaceuticals Inc OLIGOMER-CONJUGATE COMPLEXES AND THEIR USE
CA2849273C (en) * 2011-09-20 2020-07-21 Isis Pharmaceuticals, Inc. Antisense modulation of gcgr expression
AU2012328680A1 (en) 2011-10-25 2014-05-01 Ionis Pharmaceuticals, Inc. Antisense modulation of GCCR expression
DK3301177T3 (da) 2011-11-18 2020-06-15 Alnylam Pharmaceuticals Inc Rnai-midler, sammensætninger og fremgangsmåder til anvendelse deraf til behandling af transthyretin (ttr)-forbundne sygdomme
JP2015507924A (ja) 2012-02-08 2015-03-16 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 第ｖｉｉ因子の発現を調節するための方法と組成物
US9340784B2 (en) 2012-03-19 2016-05-17 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating alpha-1-antitrypsin expression
WO2013142571A2 (en) 2012-03-20 2013-09-26 Cornell University Assays for the identification of compounds that modulate lipid homeostasis
US9133461B2 (en) 2012-04-10 2015-09-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the ALAS1 gene
WO2013159109A1 (en) 2012-04-20 2013-10-24 Isis Pharmaceuticals, Inc. Modulation of hepatitis b virus (hbv) expression
EP3336189A1 (en) 2012-04-20 2018-06-20 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
TWI595885B (zh) 2012-05-02 2017-08-21 喜納製藥公司 包含四ｇａｌｎａｃ之新穎結合物及傳送寡核苷酸之方法
WO2013165816A2 (en) 2012-05-02 2013-11-07 Merck Sharp & Dohme Corp. SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS
US20160002624A1 (en) 2012-05-17 2016-01-07 Isis Pharmaceuticals, Inc. Antisense oligonucleotide compositions
US9574193B2 (en) 2012-05-17 2017-02-21 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein (a) expression
RU2748495C2 (ru) 2012-05-24 2021-05-26 Ионис Фармасьютикалз, Инк. Способы и композиции для модулирования экспрессии аполипопротеина (а)
US20150322428A1 (en) 2012-06-18 2015-11-12 Isis Pharmaceuticals, Inc. Compounds and methods for improved cellular uptake of antisense compounds
US10086081B2 (en) 2012-08-06 2018-10-02 Alnylam Pharmaceuticals, Inc. Carbohydrate conjugated RNA agents and process for their preparation
US9695418B2 (en) 2012-10-11 2017-07-04 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleosides and uses thereof
EP2920304B1 (en) 2012-11-15 2019-03-06 Roche Innovation Center Copenhagen A/S Oligonucleotide conjugates
WO2014118272A1 (en) 2013-01-30 2014-08-07 Santaris Pharma A/S Antimir-122 oligonucleotide carbohydrate conjugates
EP2951305B1 (en) 2013-01-30 2018-08-15 F.Hoffmann-La Roche Ag Lna oligonucleotide carbohydrate conjugates
EP2992098B1 (en) 2013-05-01 2019-03-27 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating hbv and ttr expression
WO2014184973A1 (ja) 2013-05-16 2014-11-20 大日本住友製薬株式会社 神経前駆細胞を用いた細胞治療における移植補助剤
EP3730619A1 (en) 2013-06-21 2020-10-28 Ionis Pharmaceuticals, Inc. Compositions and methods for modulation of target nucleic acids
SG10201908122XA (en) 2013-06-27 2019-10-30 Roche Innovation Ct Copenhagen As Antisense oligomers and conjugates targeting pcsk9
MX2015017863A (es) 2013-07-02 2016-11-30 Ionis Pharmaceuticals Inc Moduladores de receptor de hormona de crecimiento.
EP3019200B1 (en) 2013-07-11 2022-03-23 Alnylam Pharmaceuticals, Inc. Oligonucleotide-ligand conjugates and process for their preparation
CN105744959B (zh) 2013-09-13 2020-12-01 Ionis制药公司 补体因子b的调节剂
US9943604B2 (en) 2013-09-20 2018-04-17 Ionis Pharmaceuticals, Inc. Targeted therapeutic nucleosides and their use
MX2016005855A (es) 2013-11-14 2016-07-13 Roche Innovation Ct Copenhagen As Compuestos de conjugados antisentido de apolipoproteina b (apob).
US10150965B2 (en) 2013-12-06 2018-12-11 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of transthyretin (TTR) by double-stranded RNA
KR102369736B1 (ko) 2014-05-01 2022-03-02 아이오니스 파마수티컬즈, 인코포레이티드 보체 인자 b 발현을 조절하기 위한 조성물 및 방법
JP6667453B2 (ja) 2014-05-01 2020-03-18 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． 成長ホルモン受容体発現を調節するための組成物及び方法
BR122020024443B1 (pt) 2014-05-01 2022-02-22 Ionis Pharmaceuticals, Inc Composto e composição farmacêutica para modulação da expressão de angptl3
EP4223315A3 (en) 2014-05-01 2023-08-23 Ionis Pharmaceuticals, Inc. Method for synthesis of reactive conjugate clusters
DK3137091T3 (da) 2014-05-01 2021-01-25 Ionis Pharmaceuticals Inc Konjugater af modificerede antisense-oligonukleotider og anvendelse deraf til modulation af pkk-ekspression
WO2015179693A1 (en) 2014-05-22 2015-11-26 Isis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
WO2015188194A1 (en) 2014-06-06 2015-12-10 Isis Pharmaceuticals, Inc. Compositions and methods for enhanced intestinal absorption of conjugated oligomeric compounds
BR122023026882A2 (pt) * 2015-11-06 2024-01-23 Ionis Pharmaceuticals, Inc Uso de um composto oligomérico
WO2017079745A1 (en) * 2015-11-06 2017-05-11 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds for use in therapy

Also Published As

Publication number Publication date
CN110042098A (zh) 2019-07-23
US20210395734A1 (en) 2021-12-23
CN108064162A (zh) 2018-05-22
JP2018027091A (ja) 2018-02-22
IL242126B (en) 2019-01-31
US20200224198A1 (en) 2020-07-16
AU2014259756A1 (en) 2015-10-22
US9163239B2 (en) 2015-10-20
NZ631552A (en) 2017-02-24
KR20230113835A (ko) 2023-08-01
EP2991661B1 (en) 2019-03-13
KR102315836B1 (ko) 2021-10-22
PT2992098T (pt) 2019-07-05
EP3524680A1 (en) 2019-08-14
IL296543A (en) 2022-11-01
KR20210037752A (ko) 2021-04-06
ZA201507218B (en) 2023-09-27
JP2020058370A (ja) 2020-04-16
AU2020217347A1 (en) 2020-08-27
RU2015151204A (ru) 2017-06-02
AU2020207820A1 (en) 2020-08-06
KR102212275B1 (ko) 2021-02-05
CA2921509A1 (en) 2014-11-06
IL284593A (en) 2021-08-31
IL242132B (en) 2018-10-31
RU2015151202A3 (es) 2018-03-27
US10927372B2 (en) 2021-02-23
US20160076032A1 (en) 2016-03-17
US10683499B2 (en) 2020-06-16
JP2020007361A (ja) 2020-01-16
KR102235678B1 (ko) 2021-04-05
MX2021008901A (es) 2021-08-19
US20160090595A1 (en) 2016-03-31
KR20230006933A (ko) 2023-01-11
KR20180051678A (ko) 2018-05-16
ME03390B (me) 2020-01-20
RU2018136140A3 (es) 2022-04-27
RU2015151199A (ru) 2017-06-05
IL284593B2 (en) 2023-02-01
BR112015027321A8 (pt) 2018-01-02
EP4155403A1 (en) 2023-03-29
MX2015015239A (es) 2016-10-03
AU2024200296A1 (en) 2024-02-08
US9957504B2 (en) 2018-05-01
JP6652602B2 (ja) 2020-02-26
US20160076030A1 (en) 2016-03-17
CL2015003217A1 (es) 2016-07-08
ES2730015T3 (es) 2019-11-07
CA2921162A1 (en) 2014-11-06
JP6639629B2 (ja) 2020-02-05
JP2024010070A (ja) 2024-01-23
NZ728517A (en) 2021-12-24
MX2015015264A (es) 2016-08-12
IL242124B (en) 2019-02-28
EP2992097A4 (en) 2017-01-04
RS60796B1 (sr) 2020-10-30
JP2020039355A (ja) 2020-03-19
KR20200090966A (ko) 2020-07-29
CN105378082A (zh) 2016-03-02
US20180273952A1 (en) 2018-09-27
US20140343123A1 (en) 2014-11-20
AU2020233603A1 (en) 2020-10-01
RU2686080C2 (ru) 2019-04-24
CA2921514C (en) 2023-10-24
JP2024116224A (ja) 2024-08-27
MX2015015234A (es) 2016-10-03
DK2992009T3 (da) 2020-09-14
BR112015027377A2 (pt) 2017-08-29
PL2992098T3 (pl) 2019-09-30
SG11201508870VA (en) 2015-11-27
JP2021107408A (ja) 2021-07-29
ES2778442T3 (es) 2020-08-10
US20160017323A1 (en) 2016-01-21
EP3690049A1 (en) 2020-08-05
PE20161430A1 (es) 2017-01-06
JP6387084B2 (ja) 2018-09-05
RS58981B1 (sr) 2019-08-30
EP2991656A2 (en) 2016-03-09
CL2016002262A1 (es) 2017-06-09
HRP20201378T1 (hr) 2020-11-27
CN105378085B (zh) 2019-02-15
BR112015027322A2 (pt) 2017-09-26
IL283660A (en) 2021-07-29
US10883104B2 (en) 2021-01-05
AU2014259756B2 (en) 2017-02-23
KR20210129257A (ko) 2021-10-27
AU2014259757B2 (en) 2017-03-02
CR20150612A (es) 2016-03-03
AU2019204784A1 (en) 2019-07-25
MX2020004209A (es) 2020-08-13
AU2019203674A1 (en) 2019-06-27
IL270464B (en) 2021-07-29
US20210130823A1 (en) 2021-05-06
AU2019204784B2 (en) 2022-01-27
WO2014179625A1 (en) 2014-11-06
EP2991661A1 (en) 2016-03-09
HK1221475A1 (zh) 2017-06-02
EP2992009A1 (en) 2016-03-09
PT3524680T (pt) 2021-01-04
EP2992097A2 (en) 2016-03-09
EP3633039A1 (en) 2020-04-08
WO2014179626A3 (en) 2015-02-26
AU2017200365B2 (en) 2018-11-08
KR20220108195A (ko) 2022-08-02
US11299736B1 (en) 2022-04-12
AU2017203436A1 (en) 2017-06-08
IL264241B (en) 2020-04-30
MX2021008899A (es) 2021-08-19
AU2014259755A1 (en) 2015-10-22
RU2019124314A (ru) 2019-08-21
NZ753018A (en) 2022-01-28
KR20160002975A (ko) 2016-01-08
RU2697152C2 (ru) 2019-08-12
PH12019501191A1 (en) 2021-03-01
BR112015027369A8 (pt) 2018-01-02
AU2019200820A1 (en) 2019-02-28
HK1221403A1 (zh) 2017-06-02
IL242125B (en) 2019-02-28
CY1121879T1 (el) 2020-10-14
US20150126719A1 (en) 2015-05-07
SI2992009T1 (sl) 2020-10-30
JP2021020901A (ja) 2021-02-18
NZ712737A (en) 2021-08-27
PT2992009T (pt) 2020-09-21
IL273184B (en) 2021-07-29
EA201891479A1 (ru) 2018-11-30
WO2014179627A9 (en) 2015-02-26
CA2921514A1 (en) 2014-11-06
JP2020039354A (ja) 2020-03-19
US9181550B2 (en) 2015-11-10
US9181549B2 (en) 2015-11-10
AU2022202770A1 (en) 2022-05-19
KR102558571B1 (ko) 2023-07-21
HRP20190987T1 (hr) 2019-09-20
EP2991661A4 (en) 2017-02-15
CN110079524A (zh) 2019-08-02
WO2014179620A1 (en) 2014-11-06
IL284000A (en) 2021-07-29
JP7339294B2 (ja) 2023-09-05
US20180044676A1 (en) 2018-02-15
IL273184A (en) 2020-04-30
RU2670614C2 (ru) 2018-10-24
CN114058617A (zh) 2022-02-18
JP2020074787A (ja) 2020-05-21
UA121017C2 (uk) 2020-03-25
IL273205A (en) 2020-04-30
NZ631537A (en) 2017-05-26
EP2991656B1 (en) 2019-12-18
IL264580A (en) 2019-02-28
JP2016526874A (ja) 2016-09-08
HK1221404A1 (zh) 2017-06-02
KR20190084138A (ko) 2019-07-15
EP2992097B1 (en) 2019-11-06
AU2014259755B2 (en) 2018-08-30
BR112015027377A8 (pt) 2017-10-03
JP6592486B2 (ja) 2019-10-16
IL274064A (en) 2020-06-30
ZA201507216B (en) 2017-08-30
IL272617A (en) 2020-03-31
IL264241A (en) 2019-02-28
US20180002693A1 (en) 2018-01-04
BR112015027369A2 (pt) 2017-09-26
AU2014259757A1 (en) 2015-10-22
CN105377887B (zh) 2020-11-03
JP6216444B2 (ja) 2017-10-18
JP6769866B2 (ja) 2020-10-14
CN110066795A (zh) 2019-07-30
RU2650510C2 (ru) 2018-04-16
US20230151365A1 (en) 2023-05-18
EP3546579A1 (en) 2019-10-02
US9127276B2 (en) 2015-09-08
JP6456362B2 (ja) 2019-01-23
US20160090596A1 (en) 2016-03-31
CY1123369T1 (el) 2021-12-31
JP6866459B2 (ja) 2021-04-28
EP2992098B1 (en) 2019-03-27
AU2017200950B2 (en) 2019-01-17
WO2014179629A3 (en) 2015-01-22
JP2023113843A (ja) 2023-08-16
WO2014179627A3 (en) 2015-04-16
MX2019010443A (es) 2019-10-17
US11851655B2 (en) 2023-12-26
CA2921518A1 (en) 2014-11-06
AU2021204244A1 (en) 2021-07-22
KR20160002974A (ko) 2016-01-08
PE20152002A1 (es) 2016-01-21
CN112921036A (zh) 2021-06-08
RU2015151200A3 (es) 2019-01-14
SG10201801813YA (en) 2018-04-27
EP2992009B1 (en) 2020-06-24
BR112015027321A2 (pt) 2017-09-26
JP2016523515A (ja) 2016-08-12
KR102138781B1 (ko) 2020-07-28
US20220275365A9 (en) 2022-09-01
EP2991656A4 (en) 2017-02-22
NZ740338A (en) 2022-04-29
AU2017200365C1 (en) 2019-04-18
BR112015027369B1 (pt) 2021-06-08
CN110042098B (zh) 2023-02-24
US9932580B2 (en) 2018-04-03
JP2023012548A (ja) 2023-01-25
US20210087566A1 (en) 2021-03-25
BR112015027377B1 (pt) 2023-01-10
IL274064B (en) 2021-06-30
IL273312A (en) 2020-04-30
AU2014259750B2 (en) 2019-02-28
AU2017200365A1 (en) 2017-02-23
DK3524680T3 (da) 2020-12-14
MX2015015263A (es) 2016-12-16
SG10201906382QA (en) 2019-08-27
EA036584B1 (ru) 2020-11-26
BR112015027319A8 (pt) 2018-01-02
US10844379B2 (en) 2020-11-24
DK2992098T3 (da) 2019-06-17
CN113293163A (zh) 2021-08-24
US9714421B2 (en) 2017-07-25
BR112015027322A8 (pt) 2018-01-02
AU2019200820B2 (en) 2020-04-30
CN105378085A (zh) 2016-03-02
NZ725538A (en) 2021-02-26
MY178929A (en) 2020-10-23
JP7177127B2 (ja) 2022-11-22
IL263843A (en) 2019-01-31
AU2019204784C1 (en) 2022-11-03
AU2017200950A1 (en) 2017-03-02
AU2018267625A1 (en) 2018-12-13
JP2016522683A (ja) 2016-08-04
RU2015151204A3 (es) 2018-03-27
US20150126720A1 (en) 2015-05-07
EP2992009A4 (en) 2016-12-28
AU2017203436B2 (en) 2018-10-18
US20150176007A1 (en) 2015-06-25
CN108064162B (zh) 2021-12-03
KR20210151260A (ko) 2021-12-13
JP7429103B2 (ja) 2024-02-07
RU2699985C2 (ru) 2019-09-11
CN111593051A (zh) 2020-08-28
AU2014259759A1 (en) 2015-10-22
IL264580B (en) 2020-04-30
EP3524680B1 (en) 2020-11-11
IL261901A (en) 2018-10-31
EP2992098A4 (en) 2017-01-11
CN105377887A (zh) 2016-03-02
MX2019010441A (es) 2019-10-17
AU2014259759B2 (en) 2020-06-18
JP2019056001A (ja) 2019-04-11
RU2019110030A (ru) 2019-05-06
DOP2021000095A (es) 2021-09-15
EP3828275A1 (en) 2021-06-02
RU2015151202A (ru) 2017-06-06
PH12015502493B1 (en) 2016-02-22
SI2992098T1 (sl) 2019-06-28
JP2016522817A (ja) 2016-08-04
CN105392488A (zh) 2016-03-09
WO2014179629A2 (en) 2014-11-06
KR20160002976A (ko) 2016-01-08
ES2819213T3 (es) 2021-04-15
UA120287C2 (uk) 2019-11-11
AU2018267625B2 (en) 2020-09-10
BR122018009831B1 (pt) 2021-12-21
LT2992098T (lt) 2019-07-10
AU2021204244B2 (en) 2023-10-19
KR20240042220A (ko) 2024-04-01
WO2014179627A2 (en) 2014-11-06
JP2016526018A (ja) 2016-09-01
DOP2016000287A (es) 2017-02-15
US9932581B2 (en) 2018-04-03
US20240247260A1 (en) 2024-07-25
RU2018136140A (ru) 2018-12-17
PH12018501963A1 (en) 2020-07-20
HUE043697T2 (hu) 2019-09-30
US20150126718A1 (en) 2015-05-07
SG10201801507RA (en) 2018-03-28
JP2022017514A (ja) 2022-01-25
US20190055554A1 (en) 2019-02-21
KR20160003723A (ko) 2016-01-11
PL2992009T3 (pl) 2020-11-30
RU2018112167A (ru) 2019-03-07
PH12015502493A1 (en) 2016-02-22
US20180273953A1 (en) 2018-09-27
ES2885174T3 (es) 2021-12-13
JP6995478B2 (ja) 2022-01-14
JP2021074021A (ja) 2021-05-20
SG11201508800WA (en) 2015-11-27
IL263843B (en) 2020-03-31
EP2992098A2 (en) 2016-03-09
KR20210014758A (ko) 2021-02-09
AU2019202598A1 (en) 2019-05-02
IL284593B (en) 2022-10-01
KR102482890B1 (ko) 2022-12-30
CN105378082B (zh) 2020-06-09
NZ631512A (en) 2016-10-28
MX2015015220A (es) 2016-01-12
MY198359A (en) 2023-08-28
MX2020002184A (es) 2020-07-14
RU2670614C9 (ru) 2018-11-23
AU2014259750A1 (en) 2015-10-22
IL261901B (en) 2020-05-31
HK1221486A1 (zh) 2017-06-02
US9145558B2 (en) 2015-09-29
RU2015151200A (ru) 2019-01-14
EA031393B1 (ru) 2018-12-28
KR102424855B1 (ko) 2022-07-26
AU2019203674B2 (en) 2021-03-25
HUE050394T2 (hu) 2020-11-30
EA201592093A1 (ru) 2016-06-30
WO2014179629A8 (en) 2016-06-02
LT2992009T (lt) 2020-11-10
HK1221485A1 (zh) 2017-06-02
JP2018183184A (ja) 2018-11-22
WO2014179626A2 (en) 2014-11-06
DOP2015000268A (es) 2015-11-30
KR20160002977A (ko) 2016-01-08
RU2015151203A (ru) 2017-06-02
CA2921167A1 (en) 2014-11-06
RU2015151199A3 (es) 2018-03-27
BR112015027319A2 (pt) 2017-09-26
US20210024923A1 (en) 2021-01-28
KR102651423B1 (ko) 2024-03-27
US20190367914A1 (en) 2019-12-05
DK2991656T3 (da) 2020-03-23
CN105392488B (zh) 2021-04-30
KR101857707B1 (ko) 2018-05-14

Similar Documents

Publication Publication Date Title
PH12019501191A1 (en) Compositions and methods for modulating hbv and ttr expression
EA201690780A1 (ru) Пегилированные лекарственные средства-линкеры для улучшенной фармакокинетики конъюгатов лиганд-лекарственное средство
UY34804A (es) Inhibidores del nampt
EA202092987A3 (ru) Липид, содержащий докозапентаеновую кислоту
UY34697A (es) Métodos para preparar análogos de nucleótidos
CL2013000028S1 (es) Conector
UA118666C2 (uk) Похідні піразолу
UY34582A (es) Anticuerpos anti-cxcr3
CL2017002427A1 (es) Producción de ácido ribonucleico libre de células.
BR112013025866A2 (pt) formulações com viscosidade reduzida
CR20150257A (es) Derivados de n-(piridin-2-il)pirimidin-4-amina que contiene un grupo sulfoximina
BR112018009225A2 (pt) conjugados de anticorpo anti-cd22-maitansina e métodos de uso dos mesmos
BR112016011899A2 (pt) Processo para preparação de 5-fluoro-1h-pirazóis
RU2012151073A (ru) Способ стабилизации раствора дигидрокверцетина
MX2015016766A (es) Nuevos derivados de tetrazolona.
UY4241Q (es) Mesa
BR112016007306A2 (pt) uso do odiparcil no tratamento da mucopolissacaridose
BR112014005492A2 (pt) composições estáveis e métodos para preparar as mesmas
EA201992461A2 (ru) Композиции и способы модулирования экспрессии hbv и ttr
TWD155524S (zh) 髮夾
TWD158991S (zh) 雷射測速器（三）
CL2011003000S1 (es) Mesa .