CO2018002198A2 - Composiciones farmacéuticas que comprenden un compuesto oligomérico para modular la expresión de apolipoproteína (a) - Google Patents

Composiciones farmacéuticas que comprenden un compuesto oligomérico para modular la expresión de apolipoproteína (a)

Info

Publication number
CO2018002198A2
CO2018002198A2 CONC2018/0002198A CO2018002198A CO2018002198A2 CO 2018002198 A2 CO2018002198 A2 CO 2018002198A2 CO 2018002198 A CO2018002198 A CO 2018002198A CO 2018002198 A2 CO2018002198 A2 CO 2018002198A2
Authority
CO
Colombia
Prior art keywords
apo
disorders
apolipoprotein
oligomeric compounds
conjugated
Prior art date
Application number
CONC2018/0002198A
Other languages
English (en)
Inventor
Nicholas J Viney
Richard S Geary
Yanfeng Wang
Zhengrong Yu
Rudy Gunawan
Original Assignee
Ionis Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ionis Pharmaceuticals Inc filed Critical Ionis Pharmaceuticals Inc
Publication of CO2018002198A2 publication Critical patent/CO2018002198A2/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/775—Apolipopeptides
    • 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
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • 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
    • C12N2310/34—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
    • C12N2310/35—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
    • C12N2310/3515—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
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/32—Special delivery means, e.g. tissue-specific
    • 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
    • C12N2320/35—Special therapeutic applications based on a specific dosage / administration regimen

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biophysics (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Dermatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Saccharide Compounds (AREA)

Abstract

RESUMEN En la presente, se proporcionan compuestos oligoméricos con grupos conjugados dirigidos a apolipoproteína (a) [apo(a)]. En determinadas modalidades, los compuestos oligoméricos dirigidos a apo(a) están conjugados a N-acetilgalactosamina. Además, en la presente se describen compuestos oligoméricos conjugados dirigidos a apo(a) para su uso para disminuir la apo(a) para tratar, prevenir o mejorar enfermedades, trastornos o afecciones relacionadas con apo(a) y/o Lp(a). Determinadas enfermedades, trastornos o afecciones relacionadas con apo(a) y/o Lp(a) incluyen enfermedades, trastornos o afecciones inflamatorios, cardiovasculares y/o metabólicos. Los compuestos oligoméricos conjugados descritos en la presente se pueden utilizar para tratar dichas enfermedades, trastornos o afecciones en un individuo que lo necesita.
CONC2018/0002198A 2015-11-06 2018-02-27 Composiciones farmacéuticas que comprenden un compuesto oligomérico para modular la expresión de apolipoproteína (a) CO2018002198A2 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562252392P 2015-11-06 2015-11-06
PCT/US2016/060816 WO2017079739A1 (en) 2015-11-06 2016-11-07 MODULATING APOLIPOPROTEIN (a) EXPRESSION

Publications (1)

Publication Number Publication Date
CO2018002198A2 true CO2018002198A2 (es) 2018-05-10

Family

ID=58662931

Family Applications (1)

Application Number Title Priority Date Filing Date
CONC2018/0002198A CO2018002198A2 (es) 2015-11-06 2018-02-27 Composiciones farmacéuticas que comprenden un compuesto oligomérico para modular la expresión de apolipoproteína (a)

Country Status (15)

Country Link
US (3) US10557137B2 (es)
EP (1) EP3370708A4 (es)
JP (3) JP7486920B2 (es)
KR (1) KR20180073606A (es)
CN (2) CN113952353A (es)
AU (3) AU2016349625B2 (es)
BR (2) BR122023026882A2 (es)
CA (1) CA2999341A1 (es)
CL (1) CL2018001221A1 (es)
CO (1) CO2018002198A2 (es)
IL (2) IL257647B (es)
MX (2) MX2018005277A (es)
PE (2) PE20241347A1 (es)
WO (1) WO2017079739A1 (es)
ZA (1) ZA201801208B (es)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013173789A2 (en) 2012-05-17 2013-11-21 Isis Pharmaceuticals, Inc. Antisense oligonucleotide compositions
RU2686080C2 (ru) * 2013-05-01 2019-04-24 Ионис Фармасьютикалз, Инк. Композиции и способы
EP3371201A4 (en) * 2015-11-06 2019-09-18 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds for use in therapy
AU2019377275A1 (en) 2018-11-09 2021-03-25 Novartis Ag Method for reducing the risk of a cardiovascular event with conjugated antisense compounds targeting apo(a)
WO2023180904A1 (en) * 2022-03-21 2023-09-28 Crispr Therapeutics Ag Methods and compositions for treating lipoprotein-related diseases

Family Cites Families (218)

* 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
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
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
FR2567892B1 (fr) 1984-07-19 1989-02-17 Centre Nat Rech Scient Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons
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
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
US5506337A (en) 1985-03-15 1996-04-09 Antivirals Inc. Morpholino-subunit combinatorial library and method
JP2828642B2 (ja) 1987-06-24 1998-11-25 ハワード フローレイ インスティテュト オブ イクスペリメンタル フィジオロジー アンド メディシン ヌクレオシド誘導体
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
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
ATE190981T1 (de) 1989-10-24 2000-04-15 Isis Pharmaceuticals Inc 2'-modifizierte nukleotide
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences 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
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
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
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
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
EP0455905B1 (en) 1990-05-11 1998-06-17 Microprobe Corporation Dipsticks for nucleic acid hybridization assays and methods for covalently immobilizing oligonucleotides
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5386023A (en) 1990-07-27 1995-01-31 Isis Pharmaceuticals Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling
DE69126530T2 (de) 1990-07-27 1998-02-05 Isis Pharmaceutical, Inc., Carlsbad, Calif. Nuklease resistente, pyrimidin modifizierte oligonukleotide, die die gen-expression detektieren und modulieren
US5378825A (en) 1990-07-27 1995-01-03 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs
US5223618A (en) 1990-08-13 1993-06-29 Isis Pharmaceuticals, Inc. 4'-desmethyl nucleoside analog compounds
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
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
DE59208572D1 (de) 1991-10-17 1997-07-10 Ciba Geigy Ag Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte
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
TW393513B (en) 1991-11-26 2000-06-11 Isis Pharmaceuticals Inc Enhanced triple-helix and double-helix formation with oligomers containing modified 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
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
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
ATE162198T1 (de) 1992-07-27 1998-01-15 Hybridon Inc Oligonukleotid alkylphosphonothiate
EP0677056B1 (en) 1993-01-25 1996-05-22 HYBRIDON, Inc. Oligonucleotide alkylphosphonates and alkylphosphonothioates
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
GB9304620D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Compounds
AU6449394A (en) 1993-03-30 1994-10-24 Sterling Winthrop Inc. Acyclic nucleoside analogs and oligonucleotide sequences containing them
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
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
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
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
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
JP2000501414A (ja) 1995-11-22 2000-02-08 ザ・ジョンズ・ホプキンス・ユニバーシティー 生体分子の細胞取り込みを高めるリガンド
US20030119724A1 (en) 1995-11-22 2003-06-26 Ts`O Paul O.P. 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
US6620916B1 (en) 1996-09-26 2003-09-16 Ajinomoto Co., Inc. Modified physiologically active proteins and medicinal compositions containing the same
JP3756313B2 (ja) 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
ES2242291T5 (es) 1997-09-12 2016-03-11 Exiqon A/S Análogos de nucleósidos bicíclicos y tricíclicos, nucleótidos y oligonucleótidos
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
US20030228597A1 (en) 1998-04-13 2003-12-11 Cowsert Lex M. Identification of genetic targets for modulation by oligonucleotides and generation of oligonucleotides for gene modulation
US6300319B1 (en) 1998-06-16 2001-10-09 Isis Pharmaceuticals, Inc. Targeted oligonucleotide conjugates
US6043352A (en) 1998-08-07 2000-03-28 Isis Pharmaceuticals, Inc. 2'-O-Dimethylaminoethyloxyethyl-modified oligonucleotides
US6166239A (en) 1998-09-04 2000-12-26 Isis Pharmaceuticals, Inc. Oligonucleotide protecting groups
US20030170249A1 (en) 1999-02-19 2003-09-11 Hakomori Sen-Itiroh Vaccines directed to cancer-associated carbohydrate antigens
AU781598B2 (en) 1999-04-21 2005-06-02 Alnylam Pharmaceuticals, Inc. Methods and compositions for inhibiting the function of polynucleotide sequences
ATE356824T1 (de) 1999-05-04 2007-04-15 Santaris Pharma As L-ribo-lna analoge
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
AU6605900A (en) 1999-07-16 2001-02-05 Hyseq, Inc. Novel angiopoietin materials and methods
KR20020062652A (ko) 1999-12-09 2002-07-26 상꾜 가부시키가이샤 고지혈증의 치료 또는 예방제의 시험방법
EP1244667B1 (en) 1999-12-30 2006-04-05 K.U. Leuven Research & Development Cyclohexene nucleic acids
US7491805B2 (en) 2001-05-18 2009-02-17 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
CN100406065C (zh) 2000-12-01 2008-07-30 细胞工厂治疗公司 糖基化/半乳糖基化肽、双官能接头和核苷酸单体/多聚体的缀合物以及相关的组合物和使用方法
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
CA2452458A1 (en) 2001-07-03 2003-01-16 Isis Pharmaceuticals, Inc. Nuclease resistant chimeric oligonucleotides
US7407943B2 (en) 2001-08-01 2008-08-05 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein B expression
US7227014B2 (en) 2001-08-07 2007-06-05 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein (a) expression
US7259150B2 (en) 2001-08-07 2007-08-21 Isis Pharmaceuticals, Inc. 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
US7439043B2 (en) 2001-10-10 2008-10-21 Neose Technologies, Inc. Galactosyl nucleotide sugars
MXPA04004609A (es) 2001-11-16 2004-08-12 Genentech Inc Composicion que comprende y metodo para utilizar angptl3 de proteina 3 como angiopoyetina.
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)
EP1543019A2 (en) 2002-09-11 2005-06-22 Santaris Pharma A/S Modified pna molecules
US20060035344A1 (en) 2002-10-18 2006-02-16 Pachuk Catherine J Double-stranded rna structures and constructs, and methods for generating and using the same
WO2004044132A2 (en) 2002-11-05 2004-05-27 Isis Pharmaceuticals, Inc. Modified oligonucleotides for use in rna interference
CA2504694C (en) 2002-11-05 2013-10-01 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
US20060009410A1 (en) 2002-11-13 2006-01-12 Crooke Rosanne M Effects of apolipoprotein B inhibition on gene expression profiles in animals
AU2003294281B2 (en) 2002-11-13 2010-05-20 Kastle Therapeutics, Llc Antisense modulation of apolipoprotein B expression
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
JP4152955B2 (ja) 2003-01-09 2008-09-17 ポステック・ファウンデーション 新規フォスフォアミダイト化合物
EP3450559A1 (en) 2003-03-07 2019-03-06 Alnylam Pharmaceuticals, Inc. Therapeutic compositions
US7598227B2 (en) 2003-04-16 2009-10-06 Isis Pharmaceuticals Inc. Modulation of apolipoprotein C-III expression
ES2702942T3 (es) 2003-04-17 2019-03-06 Alnylam Pharmaceuticals Inc Agentes de ARNi modificados
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
WO2004101619A1 (ja) 2003-05-15 2004-11-25 Shionogi Co., Ltd. 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
JP4731324B2 (ja) 2003-08-28 2011-07-20 武 今西 Ｎ−ｏ結合性架橋構造型新規人工核酸
WO2005027962A1 (en) 2003-09-18 2005-03-31 Isis Pharmaceuticals, Inc. 4’-thionucleosides and oligomeric compounds
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
KR20070085113A (ko) 2004-05-11 2007-08-27 가부시키가이샤 알파젠 Rna간섭을 생기게 하는 폴리뉴클레오티드, 및 이를 이용한유전자발현억제 방법
JP2008501693A (ja) 2004-06-03 2008-01-24 アイシス ファーマシューティカルズ、インク． 遺伝子調節で使用するための個別に調節された鎖を有する二本鎖組成物
CN101080419B (zh) 2004-07-20 2014-07-02 健泰科生物技术公司 利用血管生成素样4蛋白的组合物和方法
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
EP1786472B1 (en) 2004-08-10 2013-01-16 Genzyme Corporation Antisense modulation of apolipoprotein b expression
US20090203132A1 (en) 2004-09-09 2009-08-13 Swayze Eric E Pyrrolidinyl groups for attaching conjugates to oligomeric compounds
WO2006047842A2 (en) 2004-11-08 2006-05-11 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
EP1841867A1 (en) 2005-01-24 2007-10-10 Avaris AB COMPLEX CONTAINING SiRNA, ShRNA OR ANTISENSE MOLECULE AND FUNCTIONAL ENTITY, FOR IMPROVED SPECIFICITY AND DELIVERY
EP2368988A1 (en) 2005-09-19 2011-09-28 Isis Pharmaceuticals, Inc. Modulation of Glucocorticoid Receptor Expression
PL2314594T3 (pl) 2006-01-27 2014-12-31 Isis Pharmaceuticals Inc Zmodyfikowane w pozycji 6 analogi bicykliczne kwasów nukleinowych
US7569686B1 (en) 2006-01-27 2009-08-04 Isis Pharmaceuticals, Inc. Compounds and methods for synthesis of bicyclic nucleic acid analogs
JP2009536222A (ja) 2006-05-05 2009-10-08 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 Ｐｃｓｋ９の発現を調節するための化合物および方法
CA2651453C (en) 2006-05-11 2014-10-14 Isis Pharmaceuticals, Inc. 5'-modified bicyclic nucleic acid analogs
US7666854B2 (en) 2006-05-11 2010-02-23 Isis Pharmaceuticals, Inc. Bis-modified bicyclic nucleic acid analogs
CA2660052A1 (en) 2006-08-04 2008-02-07 Isis Pharmaceuticals, Inc. Compositions and methods for the modulation of jnk proteins
JP5274461B2 (ja) 2006-08-18 2013-08-28 アローヘッド リサーチ コーポレイション ポリヌクレオチドのインビボ送達のためのポリ結合体
US8658211B2 (en) 2006-08-18 2014-02-25 Arrowhead Madison Inc. Polyconjugates for in vivo delivery of polynucleotides
US8093222B2 (en) 2006-11-27 2012-01-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
PL2121751T3 (pl) 2006-12-08 2017-07-31 Lexicon Pharmaceuticals, Inc. Przeciwciała monoklonalne przeciwko ANGPTL3
US20100190837A1 (en) 2007-02-15 2010-07-29 Isis Pharmaceuticals, Inc. 5'-Substituted-2-F' Modified Nucleosides and Oligomeric Compounds Prepared Therefrom
EP2604284A1 (en) 2007-02-16 2013-06-19 KTB Tumorforschungsgesellschaft mbH Receptor And Antigen Targeted Prodrug
US8877917B2 (en) 2007-04-23 2014-11-04 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
EP2173760B2 (en) 2007-06-08 2015-11-04 Isis Pharmaceuticals, Inc. Carbocyclic bicyclic nucleic acid analogs
WO2009003009A1 (en) 2007-06-26 2008-12-31 Enanta Pharmaceuticals, Inc. Substituted pyrrolidine as anti-infectives
ES2376507T5 (es) 2007-07-05 2015-08-31 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos 6-disustituidos
WO2009067647A1 (en) 2007-11-21 2009-05-28 Isis Pharmaceuticals, Inc. Carbocyclic alpha-l-bicyclic nucleic acid analogs
CA3043911A1 (en) 2007-12-04 2009-07-02 Arbutus Biopharma Corporation Targeting lipids
EP2245039A4 (en) 2008-01-31 2012-06-06 Alnylam Pharmaceuticals Inc OPTIMIZED METHODS FOR EXPORING DSRNA TO TARGET THE PCSK9 GEN
WO2009100320A2 (en) 2008-02-07 2009-08-13 Isis Pharmaceuticals, Inc. Bicyclic cyclohexitol nucleic acid analogs
WO2009120878A2 (en) 2008-03-26 2009-10-01 Alnylam Pharmaceuticals, Inc. Non-natural ribonucleotides, and methods of use thereof
AU2009234266B2 (en) 2008-04-11 2015-08-06 Tekmira Pharmaceuticals 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
CA2737661C (en) 2008-09-23 2019-08-20 Alnylam Pharmaceuticals, Inc. Chemical modifications of monomers and oligonucleotides with cycloaddition
DK2361256T3 (da) 2008-09-24 2013-07-01 Isis Pharmaceuticals Inc Cyclohexenyl-nukleinsyreanaloger
DK2356129T3 (da) 2008-09-24 2013-05-13 Isis Pharmaceuticals Inc Substituerede alpha-L-bicykliske nukleosider
WO2010048549A2 (en) 2008-10-24 2010-04-29 Isis Pharmaceuticals, Inc. 5' and 2' bis-substituted nucleosides and oligomeric compounds prepared therefrom
EP2447274B1 (en) 2008-10-24 2017-10-04 Ionis Pharmaceuticals, Inc. Oligomeric compounds and methods
NO2355851T3 (es) 2008-11-10 2018-09-01
EP2405921A4 (en) 2009-01-26 2013-05-22 Protiva Biotherapeutics Inc COMPOSITIONS AND METHODS FOR INACTIVATION OF APOLIPOPROTEIN C-III EXPRESSION
EP3243504A1 (en) 2009-01-29 2017-11-15 Arbutus Biopharma Corporation Improved lipid formulation
AU2010221419B2 (en) 2009-03-02 2015-10-01 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
WO2010129709A1 (en) 2009-05-05 2010-11-11 Alnylam Pharmaceuticals, Inc. Lipid compositions
CA2764158A1 (en) * 2009-06-01 2010-12-09 Halo-Bio Rnai Therapeutics, Inc. Polynucleotides for multivalent rna interference, compositions and methods of use thereof
KR20230098713A (ko) 2009-06-10 2023-07-04 알닐람 파마슈티칼스 인코포레이티드 향상된 지질 조성물
CA2764832A1 (en) 2009-06-15 2010-12-23 Alnylam Pharmaceuticals, Inc. Lipid formulated dsrna targeting the pcsk9 gene
US9512164B2 (en) 2009-07-07 2016-12-06 Alnylam Pharmaceuticals, Inc. Oligonucleotide end caps
US8927513B2 (en) 2009-07-07 2015-01-06 Alnylam Pharmaceuticals, Inc. 5′ phosphate mimics
TWI458493B (zh) 2009-09-25 2014-11-01 Iner Aec Executive Yuan 新穎肝標靶藥劑與合成方法
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
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
WO2011072290A2 (en) 2009-12-11 2011-06-16 The Regents Of The University Of Michigan Targeted dendrimer-drug conjugates
ES2677969T3 (es) 2010-01-08 2018-08-07 Ionis Pharmaceuticals, Inc. Modulación de la expresión tipo angiopoyetina 3
US9198972B2 (en) 2010-01-28 2015-12-01 Alnylam Pharmaceuticals, Inc. Monomers and oligonucleotides comprising cycloaddition adduct(s)
PT2539451E (pt) 2010-02-24 2016-03-28 Arrowhead Res Corp Composições para entrega de arnsi dirigida ao alvo
WO2011115818A1 (en) 2010-03-17 2011-09-22 Isis Pharmaceuticals, Inc. 5'-substituted bicyclic nucleosides and oligomeric compounds prepared therefrom
EP2553019A1 (en) 2010-03-26 2013-02-06 Mersana Therapeutics, Inc. Modified polymers for delivery of polynucleotides, method of manufacture, and methods of use thereof
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
US9725479B2 (en) 2010-04-22 2017-08-08 Ionis Pharmaceuticals, Inc. 5′-end derivatives
CN103154014B (zh) 2010-04-28 2015-03-25 Isis制药公司 修饰核苷、其类似物以及由它们制备的寡聚化合物
US20130236968A1 (en) 2010-06-21 2013-09-12 Alnylam Pharmaceuticals, Inc. Multifunctional copolymers for nucleic acid delivery
US9290760B2 (en) 2010-09-15 2016-03-22 Alnylam Pharmaceuticals, Inc. Modified iRNA agents
US8603994B2 (en) 2010-11-11 2013-12-10 Valted, Llc 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
US8501930B2 (en) 2010-12-17 2013-08-06 Arrowhead Madison Inc. Peptide-based in vivo siRNA delivery system
EP3192800A1 (en) 2010-12-17 2017-07-19 Arrowhead Pharmaceuticals, Inc. Galactose cluster-pharmacokinetic modulator targeting moiety for sirna
MX342609B (es) 2010-12-29 2016-10-06 Hoffmann La Roche Conjugados de molecula pequeña para suministro intracelular de acidos nucleicos.
PL2697243T3 (pl) 2011-04-01 2019-05-31 Ionis Pharmaceuticals Inc Modulacja ekspresji przekaźnika sygnału i aktywatora transkrypcji 3 (stat3)
RS61447B1 (sr) 2011-04-21 2021-03-31 Glaxo Group Ltd Modulacija ekspresije virusa hepatitisa b (hbv)
US20120295961A1 (en) 2011-04-21 2012-11-22 Swayze Eric E Modulation of hepatitis b virus (hbv) expression
CN107854478A (zh) 2011-04-27 2018-03-30 Ionis制药公司 载脂蛋白ciii（apociii）表达的调节
KR20230084331A (ko) 2011-06-21 2023-06-12 알닐람 파마슈티칼스 인코포레이티드 아포리포단백질 c-iii(apoc3) 유전자의 발현 억제를 위한 조성물 및 방법
KR102395085B1 (ko) 2011-06-21 2022-05-09 알닐람 파마슈티칼스 인코포레이티드 안지오포이에틴-유사 3(ANGPTL3) iRNA 조성물 및 그 사용 방법
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
MX2014001971A (es) 2011-08-26 2014-03-31 Arrowhead Res Corp Polimeros de poli(vinilester) para suministro de acido nucleico in vivo.
US10023861B2 (en) 2011-08-29 2018-07-17 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
PE20142362A1 (es) 2011-11-18 2015-01-30 Alnylam Pharmaceuticals Inc Agentes de iarn, composiciones y metodos de uso de los mismos para tratar enfermedades asociadas con transtiretina (ttr)
CA2863958A1 (en) 2012-02-08 2013-08-15 Isis Pharmaceuticals, Inc. Methods and compositions for modulating factor vii 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
AR090906A1 (es) 2012-05-02 2014-12-17 Merck Sharp & Dohme Conjugados que contienen tetragalnac y procedimientos para la administracion de oligonucleotidos
EP3919620A1 (en) 2012-05-02 2021-12-08 Sirna Therapeutics, Inc. Short interfering nucleic acid (sina) compositions
WO2013177468A2 (en) 2012-05-24 2013-11-28 Isis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein(a) expression
US9574193B2 (en) * 2012-05-17 2017-02-21 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein (a) expression
WO2013173789A2 (en) 2012-05-17 2013-11-21 Isis Pharmaceuticals, Inc. Antisense oligonucleotide compositions
KR20150083920A (ko) 2012-11-15 2015-07-20 로슈 이노베이션 센터 코펜하겐 에이/에스 항 apob 안티센스 접합체 화합물
WO2014118272A1 (en) 2013-01-30 2014-08-07 Santaris Pharma A/S Antimir-122 oligonucleotide carbohydrate conjugates
KR20150110562A (ko) 2013-01-30 2015-10-02 에프. 호프만-라 로슈 아게 Ｌｎａ 올리고뉴클레오타이드 탄수화물 컨쥬게이트
RU2686080C2 (ru) * 2013-05-01 2019-04-24 Ионис Фармасьютикалз, Инк. Композиции и способы
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
EP3011028B1 (en) 2013-06-21 2019-06-12 Ionis Pharmaceuticals, Inc. Compositions and methods for modulation of target nucleic acids
DK3013959T3 (da) 2013-06-27 2020-02-17 Roche Innovation Ct Copenhagen As Antisense-oligomerer og konjugater målrettet pcsk9
US9585859B2 (en) 2013-10-10 2017-03-07 Amarin Pharmaceuticals Ireland Limited Compositions and methods for lowering triglycerides without raising LDL-C levels in a subject on concomitant statin therapy
EP3862362A3 (en) * 2014-05-01 2021-10-27 Ionis Pharmaceuticals, Inc. Conjugates of modified antisense oligonucleotides and their use for modulating pkk expression
KR102356388B1 (ko) * 2014-05-01 2022-01-26 아이오니스 파마수티컬즈, 인코포레이티드 안지오포이에틴-유사 3 발현을 조절하기 위한 조성물 및 방법
RS59182B1 (sr) * 2014-05-01 2019-10-31 Ionis Pharmaceuticals Inc Kompozicije i postupci za modulaciju ekspresije faktora b komplementa
EP3371201A4 (en) 2015-11-06 2019-09-18 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds for use in therapy

Also Published As

Publication number Publication date
US11319536B2 (en) 2022-05-03
US20190136233A1 (en) 2019-05-09
WO2017079739A1 (en) 2017-05-11
US20240218361A1 (en) 2024-07-04
PE20181180A1 (es) 2018-07-20
ZA201801208B (en) 2020-06-24
BR122023026882A2 (pt) 2024-01-23
JP2021185149A (ja) 2021-12-09
JP7486920B2 (ja) 2024-05-20
US20200362340A1 (en) 2020-11-19
PE20241347A1 (es) 2024-07-03
EP3370708A4 (en) 2019-06-26
CL2018001221A1 (es) 2018-12-28
AU2016349625A1 (en) 2018-03-15
EP3370708A1 (en) 2018-09-12
MX2023014444A (es) 2023-12-15
MX2018005277A (es) 2018-08-01
US10557137B2 (en) 2020-02-11
CN113952353A (zh) 2022-01-21
IL257647A (en) 2018-04-30
AU2016349625B2 (en) 2022-07-07
AU2024204501A1 (en) 2024-07-18
BR112018003291A2 (pt) 2018-09-25
CA2999341A1 (en) 2017-05-11
IL285132A (en) 2021-08-31
IL257647B (en) 2021-08-31
AU2022204221A1 (en) 2022-07-07
CN108348478A (zh) 2018-07-31
JP2023116477A (ja) 2023-08-22
JP2018531605A (ja) 2018-11-01
KR20180073606A (ko) 2018-07-02

Similar Documents

Publication Publication Date Title
BR112015027319A8 (pt) Métodos e composições para modular a expressão de apolipoproteína (a)
DOP2019000005A (es) 3-metil pirazinas 2,5-disustituidas y 3-metil pirazinas 2,5,6-trisustituidas como inhibidores alostéricos de shp2
CO2018002198A2 (es) Composiciones farmacéuticas que comprenden un compuesto oligomérico para modular la expresión de apolipoproteína (a)
CO2020005887A2 (es) Compuestos policíclicos como inhibidores alostéricos de shp2
CL2018000803A1 (es) Composiciones y métodos para inhibir la expresión génica de lpa.
CL2018002703A1 (es) Agentes de iarn, composiciones y métodos de uso de los mismos para tratar enfermedades asociadas con transtiretina (ttr). (divisional solicitud 201401291)
CL2019000819A1 (es) Compuestos y composiciones para inhibir la actividad arginasa. (divisional solicitud 201801134)
CU20170172A7 (es) 4,6-diaminoquinolin-3-carbonitrilos sustituidos útiles como agentes analgésicos, antipiréticos o antiinflamatorios y antineoplásicos
BR112015022545A2 (pt) compostos de pirazolo e os usos disso
UY37098A (es) Moduladores de ror-gamma
CU20170015A7 (es) Compuesto de (pirazolilamino) pirimidinil biciclo (3.2.1)oct-8-il
CR20150571A (es) Compuestos y composiciones terapéuticos
DOP2009000257A (es) Inhibidores de cinasa p70 s6
SV2010003713A (es) Pirimidin-5-carboxamidas sustituidas 281
DOP2018000062A (es) Piridinona dicaboxamidas para uso como inhibidores de bromodominio
GT201400059A (es) Derivados de estra-1,3,5(10),16-tetraen-3-carboxamida, proceidmientos para su preparación, preparados farmacéuticos que los contienen, así como su uso para la preparacion de medicamentos
UY35455A (es) Inhibidores tripeptidicos de la epoxicetona proteasa
MX2022001796A (es) Metodos y composiciones para inhibir los sintomas asociados con la veisalgia.
UY32954A (es) PIRIMIDINAS SUSTITUIDAS CON ADAMANTILIMINOCARBONILO COMO INHIBIDORES DE 11-ß-HSD1 826?.
GT200700020A (es) Compuestos y derivados de dibencilamina
CL2019003571A1 (es) Lipido que comprende ácido docosapentanoico. (divisional solicitud 3351-2016)
AR106227A1 (es) COMPOSICIONES Y MÉTODOS PARA INHIBIR LA EXPRESIÓN GÉNICA DEL GEN DE LA APOLIPOPROTEÍNA APO(a) (LPA)
UY35443A (es) Derivados oxindol con un sustituyente oxetano y uso de los mismos para tratar enfermedades relacionadas con la vasopresina
BR112014028667A2 (pt) métodos e composições para modular a expressão de apolipoproteína(a)
CU20100206A7 (es) Pirimidin-5-carboxamidas sustituidas 281