MX2018005277A - Modular la expresion de apolipoproteina (a). - Google Patents

Modular la expresion de apolipoproteina (a).

Info

Publication number
MX2018005277A
MX2018005277A MX2018005277A MX2018005277A MX2018005277A MX 2018005277 A MX2018005277 A MX 2018005277A MX 2018005277 A MX2018005277 A MX 2018005277A MX 2018005277 A MX2018005277 A MX 2018005277A MX 2018005277 A MX2018005277 A MX 2018005277A
Authority
MX
Mexico
Prior art keywords
apo
disorders
oligomeric compounds
diseases
conditions
Prior art date
Application number
MX2018005277A
Other languages
English (en)
Inventor
J Viney Nicholas
S Geary Richard
Wang Yanfeng
Yu Zhengrong
Gunawan Rudy
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 MX2018005277A publication Critical patent/MX2018005277A/es

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61JCONTAINERS 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
    • A61J1/00Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/05Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088Compounds having three or more nucleosides or nucleotides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088Compounds having three or more nucleosides or nucleotides
    • A61K31/7125Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/08Solutions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/06Antihyperlipidemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/775Apolipopeptides
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/11Antisense
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/31Chemical structure of the backbone
    • C12N2310/315Phosphorothioates
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/32Chemical structure of the sugar
    • C12N2310/3212'-O-R Modification
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/34Spatial arrangement of the modifications
    • C12N2310/341Gapmers, i.e. of the type ===---===
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/35Nature of the modification
    • C12N2310/351Conjugate
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/35Nature of the modification
    • C12N2310/351Conjugate
    • C12N2310/3515Lipophilic moiety, e.g. cholesterol
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/35Nature of the modification
    • C12N2310/352Nature of the modification linked to the nucleic acid via a carbon atom
    • C12N2310/3525MOE, methoxyethoxy
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00Applications; Uses
    • C12N2320/30Special therapeutic applications
    • C12N2320/32Special delivery means, e.g. tissue-specific
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00Applications; Uses
    • C12N2320/30Special therapeutic applications
    • C12N2320/35Special therapeutic applications based on a specific dosage / administration regimen

Abstract

En la presente, se proporcionan compuestos oligoméricos con grupos conjugados dirigidos a apolipoproteina (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 usarse en la disminución de 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.
MX2018005277A 2015-11-06 2016-11-07 Modular la expresion de apolipoproteina (a). MX2018005277A (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
MX2018005277A true MX2018005277A (es) 2018-08-01

Family

ID=58662931

Family Applications (1)

Application Number Title Priority Date Filing Date
MX2018005277A MX2018005277A (es) 2015-11-06 2016-11-07 Modular la expresion de apolipoproteina (a).

Country Status (15)

Country Link
US (2) US10557137B2 (es)
EP (1) EP3370708A4 (es)
JP (3) JP2018531605A (es)
KR (1) KR20180073606A (es)
CN (2) CN113952353A (es)
AU (2) AU2016349625B2 (es)
BR (2) BR122023026882A2 (es)
CA (1) CA2999341A1 (es)
CL (1) CL2018001221A1 (es)
CO (1) CO2018002198A2 (es)
IL (2) IL257647B (es)
MX (1) MX2018005277A (es)
PE (1) PE20181180A1 (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
US20160002624A1 (en) 2012-05-17 2016-01-07 Isis Pharmaceuticals, Inc. Antisense oligonucleotide compositions
CA2921514C (en) 2013-05-01 2023-10-24 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating apolipoprotein c-iii expression
EP3371201A4 (en) * 2015-11-06 2019-09-18 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds for use in therapy
CN113286885A (zh) 2018-11-09 2021-08-20 诺华股份有限公司 用靶向apo(a)的经缀合的反义化合物降低心血管事件的风险的方法
TW202403046A (zh) * 2022-03-21 2024-01-16 瑞士商Crispr治療公司 用於治療脂蛋白相關的疾病之方法及組成物

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
US5506337A (en) 1985-03-15 1996-04-09 Antivirals Inc. Morpholino-subunit combinatorial library and method
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
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
ATE113059T1 (de) 1987-06-24 1994-11-15 Florey Howard Inst Nukleosid-derivate.
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
DK0942000T3 (da) 1989-10-24 2004-11-01 Isis Pharmaceuticals Inc 2'-modificerede oligonukleotider
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
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US5587470A (en) 1990-01-11 1996-12-24 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
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
DE69032425T2 (de) 1990-05-11 1998-11-26 Microprobe Corp Teststreifen zum Eintauchen für Nukleinsäure-Hybridisierungsassays und Verfahren zur kovalenten Immobilisierung von Oligonucleotiden
US5386023A (en) 1990-07-27 1995-01-31 Isis Pharmaceuticals Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
CA2088258C (en) 1990-07-27 2004-09-14 Phillip Dan Cook Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression
US5378825A (en) 1990-07-27 1995-01-03 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5223618A (en) 1990-08-13 1993-06-29 Isis Pharmaceuticals, Inc. 4'-desmethyl nucleoside analog compounds
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
EP0538194B1 (de) 1991-10-17 1997-06-04 Novartis 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
TW393513B (en) 1991-11-26 2000-06-11 Isis Pharmaceuticals Inc Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
EP1256589A3 (en) 1991-11-26 2003-09-17 Isis Pharmaceuticals, Inc. Oligomers containing modified pyrimidines
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
WO1994002499A1 (en) 1992-07-27 1994-02-03 Hybridon, Inc. Oligonucleotide alkylphosphonothioates
ATE138384T1 (de) 1993-01-25 1996-06-15 Hybridon Inc Olionukleotidalkylphosphonate und - phosphonothioate
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
EP0691968B1 (en) 1993-03-30 1997-07-16 Sanofi 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
TW520293B (en) 1995-11-22 2003-02-11 Univ Johns Hopkins Med Delivery system to enhance cellular uptake of biomolecules
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
WO2005121371A2 (en) 2004-06-03 2005-12-22 Isis Pharmaceuticals, Inc. Double strand compositions comprising differentially modified strands for use in gene modulation
CN1231675A (zh) 1996-09-26 1999-10-13 味之素株式会社 修饰的生理活性蛋白及含有该蛋白的药物组合物
JP3756313B2 (ja) 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
CA2303299C (en) 1997-09-12 2016-02-23 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
BR0009884A (pt) 1999-04-21 2002-01-08 American Home Prod Processos e composições para a inibição da função das sequências de polinucleotìdeos
CA2372085C (en) 1999-05-04 2009-10-27 Exiqon A/S L-ribo-lna analogues
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
WO2001005825A2 (en) 1999-07-16 2001-01-25 Hyseq, Inc. Nucleic acid sequences encoding putative angiopoietin proteins
CN1433482A (zh) 1999-12-09 2003-07-30 三共株式会社 高脂血症的治疗或预防剂的检验方法
JP2003519231A (ja) 1999-12-30 2003-06-17 カー・ユ・ルーベン・リサーチ・アンド・ディベロップメント シクロヘキセン核酸
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
EP1403367A4 (en) 2001-06-08 2005-08-17 Sankyo Co A MEDICAMENT TEST METHOD FOR TREATING OR PREVENTING DISEASES SUCH AS HYPERLIPEMIA
EP1499627A2 (en) 2001-07-03 2005-01-26 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
EP1451578B1 (en) 2001-11-16 2013-08-21 Genentech, Inc. Use of angptl3 antagonists for the treatment of liver diseases
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)
WO2004024757A2 (en) 2002-09-11 2004-03-25 Santaris Pharma A/S Modified pna molecules
EP1572964A4 (en) 2002-10-18 2007-08-08 Nucleonics Inc STRUCTURES AND CONSTRUCTIONS OF DOUBLE STRANDED RNA AND METHODS FOR THEIR GENERATION AND USE
WO2004044139A2 (en) 2002-11-05 2004-05-27 Isis Parmaceuticals, Inc. Modified oligonucleotides for use in rna interference
US7696345B2 (en) 2002-11-05 2010-04-13 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
US7511131B2 (en) 2002-11-13 2009-03-31 Genzyme Corporation 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
WO2004044181A2 (en) 2002-11-13 2004-05-27 Isis Pharmaceuticals, Inc. Antisense modulation of apolipoprotein b expression
EP2305813A3 (en) 2002-11-14 2012-03-28 Dharmacon, Inc. Fuctional and hyperfunctional sirna
US20070015927A1 (en) 2003-01-09 2007-01-18 Kim Byeang H New phosphoramidite compounds
WO2004080406A2 (en) 2003-03-07 2004-09-23 Alnylam Pharmaceuticals Therapeutic compositions
US7598227B2 (en) 2003-04-16 2009-10-06 Isis Pharmaceuticals Inc. Modulation of apolipoprotein C-III expression
US7851615B2 (en) 2003-04-17 2010-12-14 Alnylam Pharmaceuticals, Inc. Lipophilic conjugated iRNA agents
US7723509B2 (en) 2003-04-17 2010-05-25 Alnylam Pharmaceuticals IRNA agents with biocleavable tethers
EP2664672A1 (en) 2003-04-17 2013-11-20 Alnylam Pharmaceuticals Inc. Modified 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
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
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
WO2005116204A1 (ja) 2004-05-11 2005-12-08 Rnai Co., Ltd. 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
HUE029170T2 (en) 2004-07-20 2017-03-28 Genentech Inc Preparations and methods for the use of angiopoietin-like protein 4
US7582744B2 (en) 2004-08-10 2009-09-01 Alnylam Pharmaceuticals, Inc. Chemically modified oligonucleotides
ES2663810T3 (es) 2004-08-10 2018-04-17 Kastle Therapeutics, Llc Métodos para modular los niveles de lipoproteínas y colesterol en humanos
WO2006031461A2 (en) 2004-09-09 2006-03-23 Isis Pharmaceuticals, Inc. Pyrrolidinyl groups for attaching conjugates to oligomeric compounds
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
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
CA2623772A1 (en) 2005-09-19 2007-03-29 Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Modulation of glucocorticoid receptor expression
US7569686B1 (en) 2006-01-27 2009-08-04 Isis Pharmaceuticals, Inc. Compounds and methods for synthesis of bicyclic nucleic acid analogs
JP5342881B2 (ja) 2006-01-27 2013-11-13 アイシス ファーマシューティカルズ, インコーポレーテッド 6−修飾された二環式核酸類似体
DK2015758T3 (da) 2006-05-05 2014-06-23 Isis Pharmaceuticals Inc Forbindelser og fremgangsmåder til modulering af ekspression af apob
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
JP2010500290A (ja) 2006-08-04 2010-01-07 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 Jnkタンパク質を調節するための組成物および方法
AU2007285782B2 (en) 2006-08-18 2010-06-24 Arrowhead Research Corporation Polyconjugates for in vivo delivery of polynucleotides
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
CA2672049C (en) 2006-12-08 2016-05-10 Lexicon Pharmaceuticals, Inc. Monoclonal antibodies against angptl3
EP2125852B1 (en) 2007-02-15 2016-04-06 Ionis Pharmaceuticals, Inc. 5'-substituted-2'-f modified nucleosides and oligomeric compounds prepared therefrom
EP2609934A1 (en) 2007-02-16 2013-07-03 KTB Tumorforschungsgesellschaft mbH Receptor And Antigen Targeted Prodrug
US8877917B2 (en) 2007-04-23 2014-11-04 Alnylam Pharmaceuticals, Inc. Glycoconjugates of RNA interference agents
US8278425B2 (en) 2007-05-30 2012-10-02 Isis Pharmaceuticals, Inc. N-substituted-aminomethylene bridged bicyclic nucleic acid analogs
WO2008154401A2 (en) 2007-06-08 2008-12-18 Isis Pharmaceuticals, Inc. Carbocyclic bicyclic nucleic acid analogs
US20090004140A1 (en) 2007-06-26 2009-01-01 Yao-Ling Qiu 4-substituted pyrrolidine as anti-infectives
AU2008272918B2 (en) 2007-07-05 2012-09-13 Isis Pharmaceuticals, Inc. 6-disubstituted bicyclic nucleic acid analogs
US8546556B2 (en) 2007-11-21 2013-10-01 Isis Pharmaceuticals, Inc Carbocyclic alpha-L-bicyclic nucleic acid analogs
AU2008333811B2 (en) 2007-12-04 2014-05-01 Alnylam Pharmaceuticals, Inc. Carbohydrate conjugates as delivery agents for oligonucleotides
AU2009241591A1 (en) 2008-01-31 2009-11-05 Alnylam Pharmaceuticals, Inc. Optimized methods for delivery of DSRNA targeting the PCSK9 gene
EP2265627A2 (en) 2008-02-07 2010-12-29 Isis Pharmaceuticals, Inc. Bicyclic cyclohexitol nucleic acid analogs
US20110130440A1 (en) 2008-03-26 2011-06-02 Alnylam Pharmaceuticals, Inc. Non-natural ribonucleotides, and methods of use thereof
US8575123B2 (en) 2008-04-11 2013-11-05 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
EP2342616A2 (en) 2008-09-23 2011-07-13 Alnylam Pharmaceuticals Inc. Chemical modifications of monomers and oligonucleotides with cycloaddition
EP2361256B1 (en) 2008-09-24 2013-04-10 Isis Pharmaceuticals, Inc. Cyclohexenyl nucleic acid analogs
DK2356129T3 (da) 2008-09-24 2013-05-13 Isis Pharmaceuticals Inc Substituerede alpha-L-bicykliske nukleosider
WO2010048585A2 (en) 2008-10-24 2010-04-29 Isis Pharmaceuticals, Inc. Oligomeric compounds and methods
EP2358397B1 (en) 2008-10-24 2020-01-01 Ionis Pharmaceuticals, Inc. 5' and 2' bis-substituted nucleosides and oligomeric compounds prepared therefrom
KR20210158864A (ko) 2008-11-10 2021-12-31 알닐람 파마슈티칼스 인코포레이티드 치료제 운반용 신규 지질 및 조성물
WO2010083615A1 (en) 2009-01-26 2010-07-29 Protiva Biotherapeutics, Inc. Compositions and methods for silencing apolipoprotein c-iii expression
AU2010208035B2 (en) 2009-01-29 2016-06-23 Arbutus Biopharma Corporation Improved lipid formulation for the delivery of nucleic acids
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
EP3097908A1 (en) 2009-05-05 2016-11-30 Arbutus Biopharma Corporation Lipid compositions
JP5875976B2 (ja) 2009-06-01 2016-03-02 ヘイロー−バイオ アールエヌエーアイ セラピューティクス, インコーポレイテッド 多価rna干渉のためのポリヌクレオチド、組成物およびそれらの使用方法
PT3431076T (pt) 2009-06-10 2021-10-26 Arbutus Biopharma Corp Formulação lipídica melhorada
MX2011013421A (es) 2009-06-15 2012-03-16 Alnylam Pharmaceuticals Inc Arnds formulado con lipido de direccionamiento del gen pcsk9.
WO2011005860A2 (en) 2009-07-07 2011-01-13 Alnylam Pharmaceuticals, Inc. 5' phosphate mimics
US9512164B2 (en) 2009-07-07 2016-12-06 Alnylam Pharmaceuticals, Inc. Oligonucleotide end caps
US8552163B2 (en) 2009-09-25 2013-10-08 Johns Hopkins University Liver-targeting agents and their synthesis
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
WO2011072290A2 (en) 2009-12-11 2011-06-16 The Regents Of The University Of Michigan Targeted dendrimer-drug conjugates
EP3421040A1 (en) 2010-01-08 2019-01-02 Ionis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
US9198972B2 (en) 2010-01-28 2015-12-01 Alnylam Pharmaceuticals, Inc. Monomers and oligonucleotides comprising cycloaddition adduct(s)
AP3284A (en) 2010-02-24 2015-05-31 Arrowhead Res Corp Compositions for targeted delivery of SIRNA
US9193752B2 (en) 2010-03-17 2015-11-24 Isis Pharmaceuticals, Inc. 5′-substituted bicyclic nucleosides and oligomeric compounds prepared therefrom
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
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
US9725479B2 (en) 2010-04-22 2017-08-08 Ionis Pharmaceuticals, Inc. 5′-end derivatives
JP6005628B2 (ja) 2010-04-28 2016-10-12 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Ionis Pharmaceuticals,Inc. 修飾ヌクレオシド、その類似体、およびこれらから調製されるオリゴマー化合物
WO2011163121A1 (en) 2010-06-21 2011-12-29 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
EP2640400A4 (en) 2010-11-19 2016-01-20 Sirna Therapeutics Inc POLYMERIC POLYMERS (AMIDE) FOR THE ADMINISTRATION OF OLIGONUCLEOTIDES
CN103492568B (zh) 2010-12-17 2017-04-12 箭头研究公司 用于siRNA的半乳糖簇‑药代动力学调节剂靶向部分
US8501930B2 (en) 2010-12-17 2013-08-06 Arrowhead Madison Inc. Peptide-based in vivo siRNA delivery system
CA3131967A1 (en) 2010-12-29 2012-07-05 F. Hoffman-La Roche Ag Small molecule conjugates for intracellular delivery of nucleic acids
PL2697243T3 (pl) 2011-04-01 2019-05-31 Ionis Pharmaceuticals Inc Modulacja ekspresji przekaźnika sygnału i aktywatora transkrypcji 3 (stat3)
WO2012145674A1 (en) 2011-04-21 2012-10-26 Isis Pharmaceuticals, Inc. Modulation of hepatitis b virus (hbv) expression
JP6042871B2 (ja) 2011-04-21 2016-12-14 アイオーニス ファーマシューティカルズ, インコーポレーテッドIonis Pharmaceuticals,Inc. B型肝炎ウイルス(hbv)発現の調節
KR20190062511A (ko) 2011-04-27 2019-06-05 아이오니스 파마수티컬즈, 인코포레이티드 아포지방단백질 ciii (apociii) 발현의 조정
CN112961855A (zh) 2011-06-21 2021-06-15 阿尔尼拉姆医药品有限公司 血管生成素样3(ANGPTL3)iRNA组合物及其使用方法
MX344807B (es) 2011-06-21 2017-01-09 Alnylam Pharmaceuticals Inc Composiciones y metodos para inhibicion de genes para alipoproteina c-iii (apoc3).
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
CA2842039A1 (en) 2011-08-26 2013-03-07 Arrowhead Research Corporation Poly(vinyl ester) polymers for in vivo nucleic acid delivery
US10023861B2 (en) 2011-08-29 2018-07-17 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
US9399775B2 (en) 2011-11-18 2016-07-26 Alnylam Pharmaceuticals, Inc. RNAi agents, compositions and methods of use thereof for treating transthyretin (TTR) associated diseases
EP2812433A4 (en) 2012-02-08 2016-01-20 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
EP3919620A1 (en) 2012-05-02 2021-12-08 Sirna Therapeutics, Inc. Short interfering nucleic acid (sina) compositions
TW201808342A (zh) 2012-05-02 2018-03-16 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
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
US20150152411A1 (en) 2012-05-24 2015-06-04 Isis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein (a) expression
US10077443B2 (en) 2012-11-15 2018-09-18 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
DK2951305T3 (en) 2013-01-30 2018-10-29 Hoffmann La Roche LNA oligonucleotide KULHYDRATKONJUGATER
CA2921514C (en) 2013-05-01 2023-10-24 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating apolipoprotein c-iii expression
AU2013389474B2 (en) 2013-05-16 2018-11-15 Sumitomo Pharma Co., Ltd. Transplantation adjuvant in cell therapy using neural progenitor cells
CA2916252A1 (en) 2013-06-21 2014-12-24 Isis Pharmaceuticals, Inc. Compositions and methods for modulation of target nucleic acids
CN112263682A (zh) 2013-06-27 2021-01-26 罗氏创新中心哥本哈根有限公司 靶向pcsk9的反义寡聚体和缀合物
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
PT3137596T (pt) * 2014-05-01 2019-09-27 Ionis Pharmaceuticals Inc Composições e métodos para modulação da expressão do factor b do complemento
PT3137605T (pt) 2014-05-01 2020-12-18 Ionis Pharmaceuticals Inc Composições e métodos para modulação da expressão de angiopoietina de tipo 3
DK3137091T3 (da) * 2014-05-01 2021-01-25 Ionis Pharmaceuticals Inc Konjugater af modificerede antisense-oligonukleotider og anvendelse deraf til modulation af pkk-ekspression
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
CA2999341A1 (en) 2017-05-11
US20190136233A1 (en) 2019-05-09
US20200362340A1 (en) 2020-11-19
US10557137B2 (en) 2020-02-11
CN113952353A (zh) 2022-01-21
CO2018002198A2 (es) 2018-05-10
AU2022204221A1 (en) 2022-07-07
BR112018003291A2 (pt) 2018-09-25
KR20180073606A (ko) 2018-07-02
CN108348478A (zh) 2018-07-31
BR122023026882A2 (pt) 2024-01-23
JP2023116477A (ja) 2023-08-22
CL2018001221A1 (es) 2018-12-28
PE20181180A1 (es) 2018-07-20
EP3370708A4 (en) 2019-06-26
IL285132A (en) 2021-08-31
AU2016349625B2 (en) 2022-07-07
ZA201801208B (en) 2020-06-24
JP2021185149A (ja) 2021-12-09
EP3370708A1 (en) 2018-09-12
AU2016349625A1 (en) 2018-03-15
IL257647B (en) 2021-08-31
IL257647A (en) 2018-04-30
WO2017079739A1 (en) 2017-05-11
US11319536B2 (en) 2022-05-03
JP2018531605A (ja) 2018-11-01

Similar Documents

Publication Publication Date Title
MX2015015234A (es) Composiciones y metodos para modular la expresion de la apolipoproteina (a).
EP3825403A3 (en) Methods and compositions for modulating apolipoprotein(a) expression
MX2018005277A (es) Modular la expresion de apolipoproteina (a).
JO3343B1 (ar) أحماض 5- أمينوتتراهيدروكوينولين-2- كربوكسيليك جديدة واستخدامها
BR112017003111A2 (pt) composições e métodos para o tratamento de distúrbios neurológicos
CL2015003731A1 (es) Inhibidores de bromodominios
MX2015009104A (es) Composiciones en solución sólida y uso en el tratamiento de enfermedades cardiovasculares.
SG10201806787VA (en) Modulators of complement factor b
MX2015009058A (es) Composiciones y metodos para tratar la inflamacion cronica y las enfermedades inflamatorias.
MX2016002378A (es) Agentes mucolíticos de ditiol.
EP4219718A3 (en) Compositions and methods for modulating complement factor b expression
AU2010236286A8 (en) Modulation of inflammatory responses by Factor XI
MX2015009045A (es) Composiciones y metodos para tratar el dolor severo.
WO2018127612A3 (en) Compositions comprising lespedeza plant extract
GB201302343D0 (en) Pharmaceutical compositions comprising 15-OHEPA and methods for using the same
PL411444A1 (pl) Regulacja genu NPVF i jego produktów: metoda modulowania stanów związanych z zaburzeniami równowagi energetycznej
MY174063A (en) Poly-l-glutamic acid drug carrier for targeting and treating kidney diseases
AU341467S (en) 2 Hole blank
KR20150002727U (ko) 온냉열 붕대
AU2012100807A4 (en) Spelling board
UA93017U (uk) Препарат "нановулін-врх"
UA68072U (ru) Средство с тромболитической, сосудоукрепляющей, мембраностабилизирущей и противовоспалительной активностью
BR112014028667A2 (pt) métodos e composições para modular a expressão de apolipoproteína(a)