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MX2023007257A - Compuestos y metodos para modular el factor xii. - Google Patents

Compuestos y metodos para modular el factor xii.

Info

Publication number
MX2023007257A
MX2023007257A MX2023007257A MX2023007257A MX2023007257A MX 2023007257 A MX2023007257 A MX 2023007257A MX 2023007257 A MX2023007257 A MX 2023007257A MX 2023007257 A MX2023007257 A MX 2023007257A MX 2023007257 A MX2023007257 A MX 2023007257A
Authority
MX
Mexico
Prior art keywords
compounds
methods
pharmaceutical compositions
ameliorate
symptom
Prior art date
Application number
MX2023007257A
Other languages
English (en)
Inventor
Huynh- Hoa Bui
Brett P Monia
Freier Susan M
Chenguang Zhao
Jeffrey R Crosby
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 MX2023007257A publication Critical patent/MX2023007257A/es

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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A—HUMAN NECESSITIES
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    • C12N2310/341—Gapmers, i.e. of the type ===---===
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    • C12N2310/35—Nature of the modification
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    • C12N2310/3525—MOE, methoxyethoxy
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    • C12N2320/10—Applications; Uses in screening processes
    • C12N2320/11—Applications; Uses in screening processes for the determination of target sites, i.e. of active nucleic acids

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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)
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Abstract

Se proporcionan compuestos, métodos y composiciones farmacéuticas para reducir la cantidad o actividad de ARN de FXII en una célula o un sujeto y, en ciertos casos, reducir la cantidad de proteína de FXII en una célula o un sujeto. Dichos compuestos, métodos y composiciones farmacéuticas son útiles para prevenir, tratar o mejorar al menos un síntoma de una afección tromboembólica. Dichas afecciones tromboembólicas incluyen, trombosis venosa profunda, trombosis venosa o arterial, embolia pulmonar, infarto de miocardio y accidente cerebrovascular. Dichos síntomas incluyen dolor, dificultad para respirar, acidez estomacal, sudor frío, fatiga, aturdimiento, mareos, hinchazón, calambres, y muerte. Dichos compuestos, métodos y composiciones farmacéuticas son útiles para prevenir, tratar o mejorar al menos un síntoma del angioedema hereditario.
MX2023007257A 2020-12-18 2021-12-17 Compuestos y metodos para modular el factor xii. MX2023007257A (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202063127616P 2020-12-18 2020-12-18
PCT/US2021/064145 WO2022133278A2 (en) 2020-12-18 2021-12-17 Compounds and methods for modulating factor xii

Publications (1)

Publication Number Publication Date
MX2023007257A true MX2023007257A (es) 2023-07-03

Family

ID=82060092

Family Applications (1)

Application Number Title Priority Date Filing Date
MX2023007257A MX2023007257A (es) 2020-12-18 2021-12-17 Compuestos y metodos para modular el factor xii.

Country Status (12)

Country Link
US (1) US12018261B2 (es)
EP (1) EP4262822A4 (es)
JP (1) JP2023554346A (es)
KR (1) KR20230121795A (es)
CN (1) CN116670280A (es)
AR (1) AR124408A1 (es)
AU (1) AU2021401424A1 (es)
CA (1) CA3205040A1 (es)
IL (1) IL303800A (es)
MX (1) MX2023007257A (es)
TW (1) TW202242111A (es)
WO (1) WO2022133278A2 (es)

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* Cited by examiner, † Cited by third party
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MX2023007257A (es) 2020-12-18 2023-07-03 Ionis Pharmaceuticals Inc Compuestos y metodos para modular el factor xii.

Family Cites Families (188)

* 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
US4500707A (en) 1980-02-29 1985-02-19 University Patents, Inc. Nucleosides useful in the preparation of polynucleotides
US5132418A (en) 1980-02-29 1992-07-21 University Patents, Inc. Process for preparing 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
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
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5506337A (en) 1985-03-15 1996-04-09 Antivirals Inc. Morpholino-subunit combinatorial library and method
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
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.
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
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
CA1340032C (en) 1987-06-24 1998-09-08 Jim Haralambidis Lucleoside 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
JP3019994B2 (ja) 1987-11-30 2000-03-15 ユニバーシティ オブ アイオワ リサーチ ファウンデーション 新規なオリゴデオキシヌクレオチド、それを使用した標的遺伝子の発現をブロックする方法、及び新規なオリゴデオキシヌクレオチド並びにそれを使用した標的遺伝子の発現を阻止する方法
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
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
WO1991006556A1 (en) 1989-10-24 1991-05-16 Gilead Sciences, Inc. 2' modified oligonucleotides
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
US5457191A (en) 1990-01-11 1995-10-10 Isis Pharmaceuticals, Inc. 3-deazapurines
US6005087A (en) 1995-06-06 1999-12-21 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US5859221A (en) 1990-01-11 1999-01-12 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US7101993B1 (en) 1990-01-11 2006-09-05 Isis Pharmaceuticals, Inc. Oligonucleotides containing 2′-O-modified purines
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
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
US5623065A (en) 1990-08-13 1997-04-22 Isis Pharmaceuticals, Inc. Gapped 2' modified oligonucleotides
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
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
EP0745689A3 (en) 1990-05-11 1996-12-11 Microprobe Corporation A dipstick for a nucleic acid hybridization assay
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5386023A (en) 1990-07-27 1995-01-31 Isis Pharmaceuticals Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5378825A (en) 1990-07-27 1995-01-03 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
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
US5223618A (en) 1990-08-13 1993-06-29 Isis Pharmaceuticals, Inc. 4'-desmethyl nucleoside analog compounds
ATE131827T1 (de) 1990-08-03 1996-01-15 Sterling Winthrop Inc Verbindungen und verfahren zur unterdrückung der genexpression
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
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
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
WO1993010820A1 (en) 1991-11-26 1993-06-10 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines
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
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
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
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
ATE155467T1 (de) 1993-03-30 1997-08-15 Sanofi Sa Acyclische nucleosid analoge und sie enthaltende oligonucleotidsequenzen
CA2159629A1 (en) 1993-03-31 1994-10-13 Sanofi 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
US5446137B1 (en) 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
PT733059E (pt) 1993-12-09 2001-03-30 Univ Jefferson Compostos e metodos para mutacoes dirigidas ao local em celulas eucarioticas
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
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
US5652356A (en) 1995-08-17 1997-07-29 Hybridon, Inc. Inverted chimeric and hybrid oligonucleotides
WO1997020563A1 (en) 1995-11-22 1997-06-12 The Johns-Hopkins University Ligands to enhance cellular uptake of biomolecules
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
USRE44779E1 (en) 1997-03-07 2014-02-25 Santaris Pharma A/S Bicyclonucleoside and oligonucleotide analogues
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
CN1273476C (zh) 1997-09-12 2006-09-06 埃克西康有限公司 寡核苷酸类似物
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
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
NZ514348A (en) 1999-05-04 2004-05-28 Exiqon As L-ribo-LNA analogues
US6525191B1 (en) 1999-05-11 2003-02-25 Kanda S. Ramasamy Conformationally constrained L-nucleosides
US7491805B2 (en) 2001-05-18 2009-02-17 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
US6426220B1 (en) 2000-10-30 2002-07-30 Isis Pharmaceuticals, Inc. Antisense modulation of calreticulin expression
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
EP1499627A2 (en) 2001-07-03 2005-01-26 ISIS Pharmaceuticals, Inc. Nuclease resistant chimeric oligonucleotides
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
EP1562971B1 (en) 2002-11-05 2014-02-12 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
WO2004044136A2 (en) 2002-11-05 2004-05-27 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2’-modified nucleosides for use in gene modulation
US10011836B2 (en) 2002-11-14 2018-07-03 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
JP2006507841A (ja) 2002-11-14 2006-03-09 ダーマコン， インコーポレイテッド 機能的ｓｉＲＮＡおよび超機能的ｓｉＲＮＡ
US7723509B2 (en) 2003-04-17 2010-05-25 Alnylam Pharmaceuticals IRNA agents with biocleavable tethers
WO2004106356A1 (en) 2003-05-27 2004-12-09 Syddansk Universitet Functionalized nucleotide derivatives
WO2005021570A1 (ja) 2003-08-28 2005-03-10 Gene Design, Inc. Ｎ−０結合性架橋構造型新規人工核酸
EP1677822B1 (en) 2003-09-18 2014-04-23 Isis Pharmaceuticals, Inc. 4'-thionucleosides and oligomeric compounds
EP1598428A1 (en) 2004-05-18 2005-11-23 Georg Dewald Methods and kits to detect Hereditary angioedema type III
WO2006066878A1 (en) 2004-12-23 2006-06-29 Csl Behring Gmbh Prevention of thrombus formation and/or stabilization
US20060148740A1 (en) 2005-01-05 2006-07-06 Prosensa B.V. Mannose-6-phosphate receptor mediated gene transfer into muscle cells
EP1954822A1 (en) 2005-11-23 2008-08-13 Georg Dewald Detection and treatment of drug associated angioedema
US7569686B1 (en) 2006-01-27 2009-08-04 Isis Pharmaceuticals, Inc. Compounds and methods for synthesis of bicyclic nucleic acid analogs
EP2314594B1 (en) 2006-01-27 2014-07-23 Isis Pharmaceuticals, Inc. 6-modified bicyclic nucleic acid analogs
US7666854B2 (en) 2006-05-11 2010-02-23 Isis Pharmaceuticals, Inc. Bis-modified bicyclic nucleic acid analogs
JP5441688B2 (ja) 2006-05-11 2014-03-12 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 ５’修飾二環式核酸類似体
AU2007310989B2 (en) 2006-10-18 2014-05-29 Isis Pharmaceuticals, Inc. Antisense compounds
US20100190837A1 (en) 2007-02-15 2010-07-29 Isis Pharmaceuticals, Inc. 5'-Substituted-2-F' Modified Nucleosides and Oligomeric Compounds Prepared Therefrom
US8278425B2 (en) 2007-05-30 2012-10-02 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
CA2692579C (en) 2007-07-05 2016-05-03 Isis Pharmaceuticals, Inc. 6-disubstituted bicyclic nucleic acid analogs
CA2696497C (en) 2007-08-15 2016-07-26 Isis Pharmaceuticals, Inc. Tetrahydropyran nucleic acid analogs
CA2703264A1 (en) 2007-10-22 2009-04-30 Georg Dewald Disorders of vasoregulation and methods of diagnosing them
WO2009067647A1 (en) 2007-11-21 2009-05-28 Isis Pharmaceuticals, Inc. Carbocyclic alpha-l-bicyclic nucleic acid analogs
JP5519523B2 (ja) 2007-12-04 2014-06-11 アルニラム ファーマスーティカルズ インコーポレイテッド オリゴヌクレオチドの送達剤としての糖質コンジュゲート
US8530640B2 (en) 2008-02-07 2013-09-10 Isis Pharmaceuticals, Inc. Bicyclic cyclohexitol nucleic acid analogs
DE102008000715B9 (de) 2008-03-17 2013-01-17 Sirs-Lab Gmbh Verfahren zur in vitro Erfasssung und Unterscheidung von pathophysiologischen Zuständen
WO2010036698A1 (en) 2008-09-24 2010-04-01 Isis Pharmaceuticals, Inc. Substituted alpha-l-bicyclic nucleosides
BRPI0920263B1 (pt) 2008-10-15 2021-09-21 Ionis Pharmaceuticals, Inc Compostos compreendendo um oligonucleotídeo modificado, composição e uso dos mesmos
EP2398480A1 (en) 2009-02-19 2011-12-28 Galapagos N.V. Methods for identifying and compounds useful for the diagnosis and treatment of diseases involving inflammation
US8883153B2 (en) 2009-03-27 2014-11-11 The Research for The State University of New York Methods for preventing and treating angioedema
EP2462153B1 (en) 2009-08-06 2015-07-29 Isis Pharmaceuticals, Inc. Bicyclic cyclohexose nucleic acid analogs
SE1050124A1 (sv) 2010-02-08 2011-08-09 Linkoping Biocontrols Ab Stabil lösning
WO2011133876A2 (en) 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising acyclic and abasic nucleosides and analogs
WO2012037254A1 (en) 2010-09-15 2012-03-22 Alnylam Pharmaceuticals, Inc. MODIFIED iRNA AGENTS
WO2012064758A2 (en) 2010-11-08 2012-05-18 Isis Pharmaceuticals, Inc. Methods for modulating factor 12 expression
EP3467109A1 (en) 2011-02-08 2019-04-10 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
WO2012170947A2 (en) 2011-06-10 2012-12-13 Isis Pharmaceuticals, Inc. Methods for modulating factor 12 expression
WO2013033230A1 (en) 2011-08-29 2013-03-07 Isis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
EP3336189A1 (en) 2012-04-20 2018-06-20 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
JP2016522674A (ja) 2012-05-16 2016-08-04 ラナ セラピューティクス インコーポレイテッド 遺伝子発現を調節するための組成物及び方法
WO2014059353A2 (en) 2012-10-11 2014-04-17 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleosides and uses thereof
SI2920304T1 (sl) 2012-11-15 2019-06-28 Roche Innovation Center Copenhagen A/S Oligonukleotidni konjugati
IL315582A (en) 2013-05-01 2024-11-01 Ionis Pharmaceuticals Inc Compositions and methods for modulating HBV and TTR expression
CN114717291A (zh) 2013-12-30 2022-07-08 阿特雷卡公司 使用核酸条形码分析与单细胞缔合的核酸
CA2979703A1 (en) * 2015-03-17 2016-09-22 Arrowhead Pharmaceuticals, Inc. Compositions and methods for inhibiting gene expression of factor xii
CN108271386B (zh) 2015-05-06 2022-07-15 阿尔尼拉姆医药品有限公司 因子XII(哈格曼因子)(F12)、激肽释放酶B、血浆(夫列契因子)1(KLKB1)和激肽原1(KNG1)iRNA组合物及其使用方法
EP3400301A4 (en) 2016-01-08 2019-11-27 Alnylam Pharmaceuticals, Inc. POLYNUCLEOTIDE AGENTS TARGETING FACTOR XII (HAGEMAN FACTOR) (F12) AND THEIR METHODS OF USE
CA3023764A1 (en) 2016-06-06 2017-12-14 Arrowhead Pharmaceuticals, Inc. 5'-cyclo-phosphonate modified nucleotides
EP3573623A4 (en) 2017-01-30 2020-11-25 Arrowhead Pharmaceuticals, Inc. COMPOSITIONS AND METHODS OF INHIBITION OF GENE EXPRESSION OF FACTOR XII
US20200208150A1 (en) 2017-07-07 2020-07-02 Alnylam Pharmaceuticals, Inc. METHODS FOR TREATING OR PREVENTING CONTACT-ACTIVATION PATHWAY-ASSOCIATED DISEASES USING iRNA COMPOSITIONS TARGETING FACTOR XII (HAGEMAN FACTOR) (F12)
GB201807014D0 (en) 2018-04-30 2018-06-13 Univ Leeds Innovations Ltd Factor xlla inhibitors
EP3799604A4 (en) * 2018-05-09 2022-09-07 Ionis Pharmaceuticals, Inc. COMPOUNDS AND METHODS FOR REDUCING FXI EXPRESSION
CN118562796A (zh) * 2019-01-18 2024-08-30 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
MX2023007257A (es) 2020-12-18 2023-07-03 Ionis Pharmaceuticals Inc Compuestos y metodos para modular el factor xii.

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