AU2009298802A1 - Chemical modifications of monomers and oligonucleotides with cycloaddition - Google Patents

Chemical modifications of monomers and oligonucleotides with cycloaddition Download PDF

Info

Publication number
AU2009298802A1
AU2009298802A1 AU2009298802A AU2009298802A AU2009298802A1 AU 2009298802 A1 AU2009298802 A1 AU 2009298802A1 AU 2009298802 A AU2009298802 A AU 2009298802A AU 2009298802 A AU2009298802 A AU 2009298802A AU 2009298802 A1 AU2009298802 A1 AU 2009298802A1
Authority
AU
Australia
Prior art keywords
linker
optionally substituted
oligonucleotide
nucleoside
independently
Prior art date
Legal status (The legal status 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 status listed.)
Abandoned
Application number
AU2009298802A
Other languages
English (en)
Other versions
AU2009298802A2 (en
Inventor
David Butler
K. Narayanannair Jayaprakash
Muthusamy Jayraman
Muthiah Manoharan
Shigeo Matsuda
Rajendra K. Pandey
Chang Geng Peng
Kallanthottathil G. Rajeev
Takeshi Yamada
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alnylam Pharmaceuticals Inc
Original Assignee
Alnylam 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 Alnylam Pharmaceuticals Inc filed Critical Alnylam Pharmaceuticals Inc
Publication of AU2009298802A1 publication Critical patent/AU2009298802A1/en
Publication of AU2009298802A2 publication Critical patent/AU2009298802A2/en
Priority to AU2016202354A priority Critical patent/AU2016202354B2/en
Abandoned legal-status Critical Current

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
    • 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
    • A61K31/713Double-stranded nucleic acids or oligonucleotides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00Antiparasitic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/04Immunostimulants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • HELECTRICITY
    • H04ELECTRIC COMMUNICATION TECHNIQUE
    • H04LTRANSMISSION OF DIGITAL INFORMATION, e.g. TELEGRAPHIC COMMUNICATION
    • H04L65/00Network arrangements, protocols or services for supporting real-time applications in data packet communication
    • H04L65/60Network streaming of media packets
    • H04L65/75Media network packet handling
    • H04L65/762Media network packet handling at the source 
    • HELECTRICITY
    • H04ELECTRIC COMMUNICATION TECHNIQUE
    • H04LTRANSMISSION OF DIGITAL INFORMATION, e.g. TELEGRAPHIC COMMUNICATION
    • H04L67/00Network arrangements or protocols for supporting network services or applications
    • H04L67/50Network services
    • H04L67/75Indicating network or usage conditions on the user display
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/543Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
    • A61K47/544Phospholipids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/14Type of nucleic acid interfering nucleic acids [NA]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/14Type of nucleic acid interfering nucleic acids [NA]
    • C12N2310/141MicroRNAs, miRNAs
    • 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
    • C12N2310/3513Protein; Peptide
    • 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
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Multimedia (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Computer Networks & Wireless Communication (AREA)
  • Neurology (AREA)
  • Signal Processing (AREA)
  • Neurosurgery (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Virology (AREA)
  • Transplantation (AREA)
  • Pulmonology (AREA)
AU2009298802A 2008-09-23 2009-09-23 Chemical modifications of monomers and oligonucleotides with cycloaddition Abandoned AU2009298802A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2016202354A AU2016202354B2 (en) 2008-09-23 2016-04-14 Chemical modifications of monomers and oligonucleotides with cycloaddition

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US9949708P 2008-09-23 2008-09-23
US61/099,497 2008-09-23
PCT/US2009/058084 WO2010039548A2 (en) 2008-09-23 2009-09-23 Chemical modifications of monomers and oligonucleotides with cycloaddition

Related Child Applications (1)

Application Number Title Priority Date Filing Date
AU2016202354A Division AU2016202354B2 (en) 2008-09-23 2016-04-14 Chemical modifications of monomers and oligonucleotides with cycloaddition

Publications (2)

Publication Number Publication Date
AU2009298802A1 true AU2009298802A1 (en) 2010-04-08
AU2009298802A2 AU2009298802A2 (en) 2011-04-14

Family

ID=42038746

Family Applications (2)

Application Number Title Priority Date Filing Date
AU2009298802A Abandoned AU2009298802A1 (en) 2008-09-23 2009-09-23 Chemical modifications of monomers and oligonucleotides with cycloaddition
AU2016202354A Active AU2016202354B2 (en) 2008-09-23 2016-04-14 Chemical modifications of monomers and oligonucleotides with cycloaddition

Family Applications After (1)

Application Number Title Priority Date Filing Date
AU2016202354A Active AU2016202354B2 (en) 2008-09-23 2016-04-14 Chemical modifications of monomers and oligonucleotides with cycloaddition

Country Status (6)

Country Link
US (3) US8962580B2 (https=)
EP (2) EP2342616A2 (https=)
JP (4) JP2012513953A (https=)
AU (2) AU2009298802A1 (https=)
CA (1) CA2737661C (https=)
WO (1) WO2010039548A2 (https=)

Families Citing this family (146)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2009298802A1 (en) * 2008-09-23 2010-04-08 Alnylam Pharmaceuticals, Inc. Chemical modifications of monomers and oligonucleotides with cycloaddition
CN102459298A (zh) * 2009-05-05 2012-05-16 阿尔特姆恩科技责任有限公司 化学可编程免疫
FR2952372B1 (fr) * 2009-11-10 2012-03-23 Centre Nat Rech Scient Nouveaux derives de mannopyranoside ayant une activite anticancereuse
US20130089884A1 (en) * 2009-12-23 2013-04-11 Life Technologies Corporation Protein Modification from the Oxidation of Clickable Polyunsaturated Fatty Acid Analogs
EP2525781A1 (en) 2010-01-22 2012-11-28 Schering Corporation Novel cationic lipids for oligonucleotide delivery
US9198972B2 (en) 2010-01-28 2015-12-01 Alnylam Pharmaceuticals, Inc. Monomers and oligonucleotides comprising cycloaddition adduct(s)
ES2524356T3 (es) 2010-07-22 2014-12-05 Gilead Sciences, Inc. Métodos y compuestos para tratar infecciones provocadas por virus Paramyxoviridae
JP2013541510A (ja) 2010-08-31 2013-11-14 メルク・シャープ・エンド・ドーム・コーポレイション 新規の単一の化学物質、およびオリゴヌクレオチドの送達方法
WO2012054784A1 (en) 2010-10-20 2012-04-26 Li-Cor, Inc. Fluorescent imaging with substituted cyanine dyes
WO2013033230A1 (en) 2011-08-29 2013-03-07 Isis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
AR088441A1 (es) 2011-09-12 2014-06-11 Idenix Pharmaceuticals Inc Compuestos de carboniloximetilfosforamidato sustituido y composiciones farmaceuticas para el tratamiento de infecciones virales
CA2850367C (en) 2011-09-30 2021-06-01 Tufts University Uridine diphosphate derivatives, compositions and methods for treating neurodegenerative disorders
EP3730618A1 (en) * 2011-11-18 2020-10-28 Alnylam Pharmaceuticals, Inc. Rnai agents, compositions and methods of use thereof for treating transthyretin (ttr) associated diseases
SG10201913554YA (en) 2011-12-22 2020-03-30 Alios Biopharma Inc Substituted nucleosides, nucleotides and analogs thereof
US20150024037A1 (en) 2012-02-16 2015-01-22 The University Of Toledo Xenoantigen-Displaying Anti-Cancer Vaccines and Method of Making
US9441007B2 (en) 2012-03-21 2016-09-13 Alios Biopharma, Inc. Substituted nucleosides, nucleotides and analogs thereof
USRE48171E1 (en) 2012-03-21 2020-08-25 Janssen Biopharma, Inc. Substituted nucleosides, nucleotides and analogs thereof
US10501513B2 (en) 2012-04-02 2019-12-10 Modernatx, Inc. Modified polynucleotides for the production of oncology-related proteins and peptides
WO2013151665A2 (en) 2012-04-02 2013-10-10 modeRNA Therapeutics Modified polynucleotides for the production of proteins associated with human disease
US9283287B2 (en) 2012-04-02 2016-03-15 Moderna Therapeutics, Inc. Modified polynucleotides for the production of nuclear proteins
US9254311B2 (en) 2012-04-02 2016-02-09 Moderna Therapeutics, Inc. Modified polynucleotides for the production of proteins
CN102675626B (zh) * 2012-04-28 2014-05-28 南京威尔化工有限公司 含三氮唑的聚乙二醇蛋白质修饰剂及其制备方法和应用
AR090905A1 (es) 2012-05-02 2014-12-17 Merck Sharp & Dohme Conjugados que contienen tetragalnac y peptidos y procedimientos para la administracion de oligonucleotidos, composicion farmaceutica
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
US9296778B2 (en) 2012-05-22 2016-03-29 Idenix Pharmaceuticals, Inc. 3′,5′-cyclic phosphate prodrugs for HCV infection
JP6165848B2 (ja) 2012-05-22 2017-07-19 イデニク ファーマシューティカルズ エルエルシー 肝疾患のためのd−アミノ酸化合物
WO2013177188A1 (en) 2012-05-22 2013-11-28 Idenix Pharmaceuticals, Inc. 3',5'-cyclic phosphoramidate prodrugs for hcv infection
MX2014014323A (es) 2012-05-25 2015-02-12 Janssen R & D Ireland Nucleosidos de espirooxetano de uracilo.
WO2014052638A1 (en) 2012-09-27 2014-04-03 Idenix Pharmaceuticals, Inc. Esters and malonates of sate prodrugs
US9163055B2 (en) 2012-09-28 2015-10-20 Tufts University Methods for treating glaucoma using uridine diphosphate derivatives
EP2906579B1 (en) 2012-10-08 2018-04-18 Idenix Pharmaceuticals LLC. 2'-chloro nucleoside analogs for hcv infection
EP2935304A1 (en) 2012-12-19 2015-10-28 IDENIX Pharmaceuticals, Inc. 4'-fluoro nucleosides for the treatment of hcv
CA2891966A1 (en) * 2012-12-20 2014-06-26 Sirna Therapeutics, Inc. Post-synthetic orthogonal amidation plus metal catalyzed azide-alkyne cycloaddition click chemistry on sirna
WO2014137930A1 (en) 2013-03-04 2014-09-12 Idenix Pharmaceuticals, Inc. Thiophosphate nucleosides for the treatment of hcv
WO2014137926A1 (en) 2013-03-04 2014-09-12 Idenix Pharmaceuticals, Inc. 3'-deoxy nucleosides for the treatment of hcv
SI2968385T1 (sl) 2013-03-13 2018-10-30 Tufts University Uridin nukleozid derivati, sestavki in metode uporabe
WO2014160484A1 (en) 2013-03-13 2014-10-02 Idenix Pharmaceuticals, Inc. Amino acid phosphoramidate pronucleotides of 2'-cyano, azido and amino nucleosides for the treatment of hcv
US10138265B2 (en) 2013-03-13 2018-11-27 Tufts University Uridine nucleoside derivatives, compositions and methods of use
EP2981542B1 (en) 2013-04-01 2021-09-15 Idenix Pharmaceuticals LLC 2',4'-fluoro nucleosides for the treatment of hcv
DK2992098T3 (da) 2013-05-01 2019-06-17 Ionis Pharmaceuticals Inc Sammensætninger og fremgangsmåder til modulering af hbv- og ttr-ekspression
US10005779B2 (en) 2013-06-05 2018-06-26 Idenix Pharmaceuticals Llc 1′,4′-thio nucleosides for the treatment of HCV
CN105492429A (zh) 2013-07-02 2016-04-13 米伦纽姆医药公司 Sumo活化酶的杂芳基抑制剂
WO2015017713A1 (en) 2013-08-01 2015-02-05 Idenix Pharmaceuticals, Inc. D-amino acid phosphoramidate pronucleotides of halogeno pyrimidine compounds for liver disease
EP2913064A1 (en) * 2014-02-26 2015-09-02 celares GmbH Branched drug-linker conjugates for the coupling to biological targeting molecules
US10202411B2 (en) 2014-04-16 2019-02-12 Idenix Pharmaceuticals Llc 3′-substituted methyl or alkynyl nucleosides nucleotides for the treatment of HCV
WO2015168172A1 (en) 2014-04-28 2015-11-05 Isis Pharmaceuticals, Inc. Linkage modified oligomeric compounds
EA036496B1 (ru) 2014-05-01 2020-11-17 Ионис Фармасьютикалз, Инк. Конъюгированные олигонуклеотиды для модулирования экспрессии фактора комплемента b
BR112016022742B1 (pt) 2014-05-01 2022-06-14 Ionis Pharmaceuticals, Inc Composto químico, composição compreendendo o composto e uso dos mesmos
HUE052709T2 (hu) 2014-05-01 2021-05-28 Ionis Pharmaceuticals Inc Módosított antiszensz oligonukleotidok konjugátumai és azok alkalmazása PKK expressziójának módosítására
US9382540B2 (en) 2014-05-01 2016-07-05 Isis Pharmaceuticals, Inc Compositions and methods for modulating angiopoietin-like 3 expression
WO2015179693A1 (en) 2014-05-22 2015-11-26 Isis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
WO2015179790A1 (en) 2014-05-23 2015-11-26 Centrillion Technology Holding Corporation Oligonucleotide probe inversion process for in situ synthesized probe arrays
BR112016030787B1 (pt) 2014-07-01 2022-12-20 Takeda Pharmaceutical Company Limited Entidade química, composição farmacêutica e seu uso
WO2016030863A1 (en) * 2014-08-29 2016-03-03 Glaxosmithkline Intellectual Property Development Limited Compounds and methods for treating viral infections
US10436802B2 (en) 2014-09-12 2019-10-08 Biogen Ma Inc. Methods for treating spinal muscular atrophy
DK3569711T3 (da) * 2014-12-15 2021-02-22 Dicerna Pharmaceuticals Inc Ligandmodificerede dobbeltstrengede nukleinsyrer
US10487103B2 (en) 2015-03-24 2019-11-26 Gifu University Oligonucleotide derivative, oligonucleotide construct using the same, and methods for producing them
MX2018000412A (es) 2015-07-10 2018-03-14 Ionis Pharmaceuticals Inc Moduladores de diaciglicerol aciltransferasa 2 (dgat2).
WO2017031278A1 (en) * 2015-08-18 2017-02-23 Centrillion Technology Holdings Corporation Probe inversion process for in situ synthesized probe arrays
US10695735B2 (en) * 2015-08-18 2020-06-30 Centrillion Technology Holdings Corporation Probe inversion process for in situ synthesized probe arrays
TWI870767B (zh) 2015-08-26 2025-01-21 比利時商健生藥品公司 使用作為prmt5抑制劑之新穎經6-6雙環芳香環取代之核苷類似物
CN108513588A (zh) 2015-09-24 2018-09-07 Ionis制药公司 Kras表达的调节剂
PL4119569T3 (pl) 2015-11-06 2024-11-18 Ionis Pharmaceuticals, Inc. Sprzężone związki antysensowne do zastosowania w terapii
KR20250078597A (ko) 2015-11-06 2025-06-02 아이오니스 파마수티컬즈, 인코포레이티드 아포리포프로테인 (a) 발현 조정
CA3011946A1 (en) 2016-03-07 2017-09-14 Arrowhead Pharmaceuticals, Inc. Targeting ligands for therapeutic compounds
US10898504B2 (en) 2016-03-10 2021-01-26 Janssen Pharmaceutica Nv Substituted nucleoside analogues for use as PRMT5 inhibitors
WO2017178656A1 (en) 2016-04-14 2017-10-19 Roche Innovation Center Copenhagen A/S TRITYL-MONO-GalNAc COMPOUNDS AND THEIR USE
WO2018013525A1 (en) 2016-07-11 2018-01-18 Translate Bio Ma, Inc. Nucleic acid conjugates and uses thereof
EP3484524B1 (en) 2016-07-15 2022-11-09 Ionis Pharmaceuticals, Inc. Compounds and methods for modulation of smn2
US10781175B2 (en) 2016-07-15 2020-09-22 Am Chemicals Llc Solid supports and phosphoramidite building blocks for oligonucleotide conjugates
CA3033867A1 (en) 2016-08-17 2018-02-22 Solstice Biologics, Ltd. Polynucleotide constructs
SG11201901841TA (en) 2016-09-02 2019-03-28 Arrowhead Pharmaceuticals Inc Targeting ligands
TN2019000087A1 (en) 2016-10-03 2020-07-15 Janssen Pharmaceutica Nv Novel monocyclic and bicyclic ring system substituted carbanucleoside analogues for use as prmt5 inhibitors
US11400161B2 (en) 2016-10-06 2022-08-02 Ionis Pharmaceuticals, Inc. Method of conjugating oligomeric compounds
KR20220150408A (ko) 2016-11-14 2022-11-10 항저우 디에이씨 바이오테크 씨오, 엘티디 결합 링커, 그러한 결합 링커를 함유하는 세포 결합 분자-약물 결합체, 링커를 갖는 그러한 결합체의 제조 및 사용
TN2019000212A1 (en) 2017-02-27 2021-01-07 Janssen Pharmaceutica Nv Use of biomarkers in identifying cancer patients that will be responsive to treatment with a prmt5 inhibitor
JOP20190215A1 (ar) 2017-03-24 2019-09-19 Ionis Pharmaceuticals Inc مُعدّلات التعبير الوراثي عن pcsk9
DK3607069T3 (da) 2017-04-05 2022-11-21 Silence Therapeutics Gmbh Produkter og sammensætninger
CN108728397B (zh) * 2017-04-17 2022-05-20 中国科学院微生物研究所 对昆虫蛋白或昆虫表达系统表达的外源蛋白进行标记的方法
CA3059777C (en) 2017-05-01 2023-02-21 Gilead Sciences, Inc. Crystalline forms of (s)-2-ethylbutyl 2-(((s)-(((2r,3s,4r,5r)-5-(4-aminopyrrolo[2,1-f] [1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy) phosphoryl)amino)propanoate
US11597744B2 (en) 2017-06-30 2023-03-07 Sirius Therapeutics, Inc. Chiral phosphoramidite auxiliaries and methods of their use
WO2019014247A1 (en) 2017-07-11 2019-01-17 Gilead Sciences, Inc. COMPOSITIONS COMPRISING POLYMERASE RNA INHIBITOR AND CYCLODEXTRIN FOR THE TREATMENT OF VIRAL INFECTIONS
US11059850B2 (en) 2017-12-08 2021-07-13 Janssen Pharmaceutica Nv Spirobicyclic analogues
WO2019140102A1 (en) 2018-01-10 2019-07-18 Translate Bio Ma, Inc. Compositions and methods for facilitating delivery of synthetic nucleic acids to cells
AU2019206731A1 (en) 2018-01-15 2020-07-30 Ionis Pharmaceuticals, Inc. Modulators of DNM2 expression
WO2019157531A1 (en) 2018-02-12 2019-08-15 Ionis Pharmaceuticals, Inc. Modified compounds and uses thereof
KR20200140274A (ko) * 2018-03-07 2020-12-15 에모리 유니버시티 4'-할로겐 함유 뉴클레오티드 및 뉴클레오시드 치료 조성물 및 이와 관련된 용도
MX2020011570A (es) 2018-05-07 2020-11-24 Alnylam Pharmaceuticals Inc Administracion extrahepatica.
CU20200082A7 (es) 2018-05-09 2021-06-08 Ionis Pharmaceuticals Inc Compuestos y métodos para la reducción de la expresión de fxi
US12496311B2 (en) 2018-07-17 2025-12-16 Aronora, Inc. Methods for safely reducing thrombopoietin
EP3833397A4 (en) 2018-08-08 2023-06-14 Arcturus Therapeutics, Inc. COMPOSITIONS AND AGENTS AGAINST NON-ALCOHOLIC STEATOHEPATITIS
TW202542311A (zh) 2018-09-19 2025-11-01 美商Ionis製藥公司 Pnpla3表現之調節劑
CR20210395A (es) 2018-12-21 2021-11-05 Ionis Pharmaceuticals Inc Moduladores de la expresión de hsd17b13
WO2020139788A2 (en) * 2018-12-28 2020-07-02 Sirnaomics, Inc. Targeted delivery of therapeutic molecules
TW202112375A (zh) 2019-06-06 2021-04-01 比利時商健生藥品公司 使用prmt5抑制劑治療癌症之方法
WO2021074772A1 (en) 2019-10-14 2021-04-22 Astrazeneca Ab Modulators of pnpla3 expression
CA3164050A1 (en) 2019-12-09 2021-06-17 Empirico Inc. Oligonucleotides for treatment of angiopoietin like 4 (angptl4) related diseases
JP2023512656A (ja) 2020-01-27 2023-03-28 ギリアード サイエンシーズ, インコーポレイテッド SARS CoV-2感染を治療するための方法
TWI775313B (zh) 2020-02-18 2022-08-21 美商基利科學股份有限公司 抗病毒化合物
TWI883391B (zh) 2020-02-18 2025-05-11 美商基利科學股份有限公司 抗病毒化合物
KR20250133471A (ko) 2020-02-18 2025-09-05 길리애드 사이언시즈, 인코포레이티드 항바이러스 화합물
CN120505310A (zh) 2020-02-28 2025-08-19 Ionis制药公司 用于调节smn2的化合物和方法
KR20220153619A (ko) 2020-03-12 2022-11-18 길리애드 사이언시즈, 인코포레이티드 1'-시아노 뉴클레오사이드의 제조 방법
CN111303235B (zh) * 2020-03-12 2021-08-13 中国科学院微生物研究所 一种抗流感病毒化合物及其制备方法与应用
WO2021188894A2 (en) * 2020-03-20 2021-09-23 University Of Massachusetts Micrornas for prevention of clinical venous thromboembolic disease
CA3172483A1 (en) 2020-04-06 2021-10-14 Scott Ellis Inhalation formulations of 1'-cyano substituted carbanucleoside analogs
EP4133076A1 (en) * 2020-04-07 2023-02-15 Alnylam Pharmaceuticals, Inc. Angiotensin-converting enzyme 2 (ace2) irna compositions and methods of use thereof
EP4133077A1 (en) 2020-04-07 2023-02-15 Alnylam Pharmaceuticals, Inc. Transmembrane serine protease 2 (tmprss2) irna compositions and methods of use thereof
CN115916262A (zh) 2020-04-21 2023-04-04 旗舰创业股份有限公司 双官能分子及其使用方法
TW202203941A (zh) 2020-05-29 2022-02-01 美商基利科學股份有限公司 瑞德西韋之治療方法
PE20230618A1 (es) 2020-06-24 2023-04-14 Gilead Sciences Inc Analogos de nucleosido de 1'-ciano y usos de los mismos
IL300412A (en) 2020-08-24 2023-04-01 Gilead Sciences Inc Phospholipid compounds and their uses
IL300453A (en) 2020-08-27 2023-04-01 Gilead Sciences Inc COMPOSITIONS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS
CA3198406A1 (en) * 2020-10-09 2022-04-14 Adarx Pharmaceuticals, Inc. N-acetylgalactosamine(galnac)-derived compounds and oligonucleotides
TW202344257A (zh) 2020-10-16 2023-11-16 美商基利科學股份有限公司 磷脂化合物及其用途
LT4136092T (lt) 2020-11-18 2024-09-25 Ionis Pharmaceuticals, Inc. Junginiai ir būdai, skirti angiotenzinogeno raiškos moduliavimui
CA3204340A1 (en) * 2021-01-30 2022-08-04 Ahmad Ali MORTAZAVI Conjugated oligonucleotide compounds, methods of making and uses thereof
JP2024504504A (ja) * 2021-01-30 2024-01-31 イー セラピューティクス パブリック リミテッド カンパニー コンジュゲートオリゴヌクレオチド化合物、その作製方法及び使用
CA3216162A1 (en) 2021-04-16 2022-10-20 Gilead Sciences, Inc. Methods of preparing carbanucleosides using amides
US11649260B2 (en) 2021-06-18 2023-05-16 Hongene Biotech Corporation Functionalized N-acetylgalactosamine nucleosides
WO2023288047A2 (en) * 2021-07-15 2023-01-19 Alnylam Pharmaceuticals, Inc. Multiplexing targeting ligands through click chemistry at the anomeric site of sugars
AU2022315530A1 (en) 2021-07-20 2024-01-18 Ags Therapeutics Sas Extracellular vesicles from microalgae, their preparation, and uses
AU2022328698B2 (en) 2021-08-18 2025-02-20 Gilead Sciences, Inc. Phospholipid compounds and methods of making and using the same
EP4396193A4 (en) 2021-08-30 2025-07-02 Hongene Biotech Corp FUNCTIONALIZED N-ACETYLGALACTOSAMINE ANALOGUES
TW202328449A (zh) 2021-09-24 2023-07-16 美商艾拉倫製藥公司 微管相關蛋白TAU(MAPT)iRNA試劑組合物及其使用方法
US12042509B2 (en) 2021-10-01 2024-07-23 Adarx Pharmaceuticals, Inc. Prekallikrein-modulating compositions and methods of use thereof
JP2024546585A (ja) 2021-12-15 2024-12-26 ホンジーン バイオテック コーポレイション 官能基化n-アセチルガラクトサミンアナログ
US20230210998A1 (en) * 2021-12-30 2023-07-06 Navidea Biopharmaceuticals, Inc. Methods for the conjugation of anthracyclines to carbohydrate polymeric carriers
WO2023144127A1 (en) 2022-01-31 2023-08-03 Ags Therapeutics Sas Extracellular vesicles from microalgae, their biodistribution upon administration, and uses
KR20240154647A (ko) 2022-03-02 2024-10-25 길리애드 사이언시즈, 인코포레이티드 바이러스성 감염 치료를 위한 화합물 및 방법
US11879125B2 (en) 2022-03-16 2024-01-23 Empirico Inc. GalNAc compositions for improving siRNA bioavailability
AU2023245603A1 (en) 2022-03-28 2024-11-07 Empirico Inc. Modified oligonucleotides
WO2023232976A1 (en) 2022-06-03 2023-12-07 Ags Therapeutics Sas Extracellular vesicles from genetically-modified microalgae containing endogenously-loaded cargo, their preparation, and uses
WO2024088808A1 (en) 2022-10-24 2024-05-02 Ags Therapeutics Sas Extracellular vesicles from microalgae, their biodistribution upon intranasal administration, and uses thereof
US12357577B1 (en) 2024-02-02 2025-07-15 Gilead Sciences, Inc. Pharmaceutical formulations and uses thereof
KR20250099265A (ko) * 2022-11-23 2025-07-01 일라이 릴리 앤드 캄파니 표적화 리간드-접합된 뉴클레오티드 포스포르아미다이트의 합성 방법
WO2024118503A1 (en) 2022-11-28 2024-06-06 Hongene Biotech Corporation Functionalized n-acetylgalactosamine analogs
TW202448484A (zh) 2023-04-20 2024-12-16 美商雅迪克斯製藥公司 Mapt調節組合物及其使用方法
WO2024238396A1 (en) 2023-05-12 2024-11-21 Adarx Pharmaceuticals, Inc. Nmda ligand conjugated compounds and uses thereof
CN121335980A (zh) 2023-05-26 2026-01-13 阿达尔克斯制药有限公司 Sod1调节组合物及其使用方法
EP4731763A1 (en) 2023-06-20 2026-04-29 Adarx Pharmaceuticals, Inc. Lrrk2-modulating compositions and methods of use thereof
AU2024325594A1 (en) * 2023-08-17 2026-02-26 Adarx Pharmaceuticals, Inc. Modified oligonucleotides containing multiple oligonucleotides
WO2025038960A1 (en) * 2023-08-17 2025-02-20 Adarx Pharmaceuticals, Inc. Oligonucleotides containing a ligand at an internal position
WO2025038963A1 (en) * 2023-08-17 2025-02-20 Adarx Pharmaceuticals, Inc. Oligonucleotides containing multiple ligands and/or lipids
CN117417400B (zh) * 2023-12-18 2024-02-20 苏州诺维康生物科技有限公司 2'-o-丙炔基-5'-二甲氧三苯甲基-n4-乙酰基-胞苷的合成方法
WO2025176843A1 (en) 2024-02-21 2025-08-28 Ags Therapeutics Sas Microalgae extracellular vesicle based gene therapy vectors (mev-gtvs), their preparation, and uses thereof

Family Cites Families (143)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5218A (en) 1847-08-07 Improvement in plows
US105A (en) 1836-12-15 knight
US1861608A (en) 1929-12-21 1932-06-07 Emerson Electric Mfg Co Fan and means for directing the air current therethrough
US1861108A (en) 1930-01-24 1932-05-31 Eugene O Brace Integral clutch and transmission control
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US3974808A (en) 1975-07-02 1976-08-17 Ford Motor Company Air intake duct assembly
DE3023787A1 (de) 1980-06-25 1982-01-21 Studiengesellschaft Kohle mbH, 4330 Mülheim Verfahren zur erhoehung der inkorporation und der expression von genetischem material in die kerne von intakten zellen mit hilfe von liposomen
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
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
JPS5927900A (ja) 1982-08-09 1984-02-14 Wakunaga Seiyaku Kk 固定化オリゴヌクレオチド
US4708708A (en) 1982-12-06 1987-11-24 International Paper Company Method and apparatus for skiving and hemming
FR2540122B1 (fr) 1983-01-27 1985-11-29 Centre Nat Rech Scient Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application
US4605735A (en) 1983-02-14 1986-08-12 Wakunaga Seiyaku Kabushiki Kaisha Oligonucleotide derivatives
US4948882A (en) 1983-02-22 1990-08-14 Syngene, Inc. Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis
US4824941A (en) 1983-03-10 1989-04-25 Julian Gordon Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems
US4587044A (en) 1983-09-01 1986-05-06 The Johns Hopkins University Linkage of proteins to nucleic acids
US5118802A (en) 1983-12-20 1992-06-02 California Institute Of Technology DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside
US4828991A (en) 1984-01-31 1989-05-09 Akzo N.V. Tumor specific monoclonal antibodies
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US5258506A (en) 1984-10-16 1993-11-02 Chiron Corporation Photolabile reagents for incorporation into oligonucleotide chains
US4828979A (en) 1984-11-08 1989-05-09 Life Technologies, Inc. Nucleotide analogs for nucleic acid labeling and detection
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
WO1986005519A1 (en) 1985-03-15 1986-09-25 James Summerton Polynucleotide assay reagent and method
US4762779A (en) 1985-06-13 1988-08-09 Amgen Inc. Compositions and methods for functionalizing nucleic acids
US5317098A (en) 1986-03-17 1994-05-31 Hiroaki Shizuya Non-radioisotope tagging of fragments
JPS638396A (ja) 1986-06-30 1988-01-14 Wakunaga Pharmaceut Co Ltd ポリ標識化オリゴヌクレオチド誘導体
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
US5585481A (en) 1987-09-21 1996-12-17 Gen-Probe Incorporated Linking reagents for nucleotide probes
US5525465A (en) 1987-10-28 1996-06-11 Howard Florey Institute Of Experimental Physiology And Medicine Oligonucleotide-polyamide conjugates and methods of production and applications of the same
DE3738460A1 (de) 1987-11-12 1989-05-24 Max Planck Gesellschaft Modifizierte oligonukleotide
US5082830A (en) 1988-02-26 1992-01-21 Enzo Biochem, Inc. End labeled nucleotide probe
US5109124A (en) 1988-06-01 1992-04-28 Biogen, Inc. Nucleic acid probe linked to a label having a terminal cysteine
US5149782A (en) 1988-08-19 1992-09-22 Tanox Biosystems, Inc. Molecular conjugates containing cell membrane-blending agents
US5262536A (en) 1988-09-15 1993-11-16 E. I. Du Pont De Nemours And Company Reagents for the preparation of 5'-tagged oligonucleotides
US5512439A (en) 1988-11-21 1996-04-30 Dynal As Oligonucleotide-linked magnetic particles and uses thereof
CA2006008C (en) 1988-12-20 2000-02-15 Donald J. Kessler Method for making synthetic oligonucleotides which bind specifically to target sites on duplex dna molecules, by forming a colinear triplex, the synthetic oligonucleotides and methods of use
US5457183A (en) 1989-03-06 1995-10-10 Board Of Regents, The University Of Texas System Hydroxylated texaphyrins
US5599923A (en) 1989-03-06 1997-02-04 Board Of Regents, University Of Tx Texaphyrin metal complexes having improved functionalization
US5391723A (en) 1989-05-31 1995-02-21 Neorx Corporation Oligonucleotide conjugates
US5256775A (en) 1989-06-05 1993-10-26 Gilead Sciences, Inc. Exonuclease-resistant oligonucleotides
US4958013A (en) 1989-06-06 1990-09-18 Northwestern University Cholesteryl modified oligonucleotides
NL8901881A (nl) 1989-07-20 1991-02-18 Rockwool Grodan Bv Drainagekoppelelement.
US5451463A (en) 1989-08-28 1995-09-19 Clontech Laboratories, Inc. Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides
US5254469A (en) 1989-09-12 1993-10-19 Eastman Kodak Company Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
EP0452457B1 (en) 1989-11-03 1997-08-20 Vanderbilt University Method of in vivo delivery of functioning foreign genes
US5292873A (en) 1989-11-29 1994-03-08 The Research Foundation Of State University Of New York Nucleic acids labeled with naphthoquinone probe
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5223168A (en) 1989-12-12 1993-06-29 Gary Holt Surface cleaner and treatment
US5130302A (en) 1989-12-20 1992-07-14 Boron Bilogicals, Inc. Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US5457191A (en) 1990-01-11 1995-10-10 Isis Pharmaceuticals, Inc. 3-deazapurines
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5212295A (en) 1990-01-11 1993-05-18 Isis Pharmaceuticals Monomers for preparation of oligonucleotides having chiral phosphorus linkages
US6153737A (en) 1990-01-11 2000-11-28 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US5506351A (en) 1992-07-23 1996-04-09 Isis Pharmaceuticals Process for the preparation of 2'-O-alkyl guanosine and related compounds
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
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
US5214136A (en) 1990-02-20 1993-05-25 Gilead Sciences, Inc. Anthraquinone-derivatives oligonucleotides
AU7579991A (en) 1990-02-20 1991-09-18 Gilead Sciences, Inc. Pseudonucleosides and pseudonucleotides and their polymers
ES2116977T3 (es) 1990-05-11 1998-08-01 Microprobe Corp Soportes solidos para ensayos de hibridacion de acidos nucleicos y metodos para inmovilizar oligonucleotidos de modo covalente.
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5378825A (en) 1990-07-27 1995-01-03 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs
US5386023A (en) 1990-07-27 1995-01-31 Isis Pharmaceuticals Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling
US5223618A (en) 1990-08-13 1993-06-29 Isis Pharmaceuticals, Inc. 4'-desmethyl nucleoside analog compounds
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
JPH0874B2 (ja) 1990-07-27 1996-01-10 アイシス・ファーマシューティカルス・インコーポレーテッド 遺伝子発現を検出および変調するヌクレアーゼ耐性、ピリミジン修飾オリゴヌクレオチド
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5688941A (en) 1990-07-27 1997-11-18 Isis Pharmaceuticals, Inc. Methods of making conjugated 4' desmethyl nucleoside analog compounds
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5245022A (en) 1990-08-03 1993-09-14 Sterling Drug, Inc. Exonuclease resistant terminally substituted oligonucleotides
US6262241B1 (en) 1990-08-13 2001-07-17 Isis Pharmaceuticals, Inc. Compound for detecting and modulating RNA activity and gene expression
US5512667A (en) 1990-08-28 1996-04-30 Reed; Michael W. Trifunctional intermediates for preparing 3'-tailed oligonucleotides
KR930702373A (ko) 1990-11-08 1993-09-08 안토니 제이. 페이네 합성 올리고누클레오티드에 대한 다중 리포터(Reporter)그룹의 첨합
US6933286B2 (en) 1991-03-19 2005-08-23 R. Martin Emanuele Therapeutic delivery compositions and methods of use thereof
US20020123476A1 (en) 1991-03-19 2002-09-05 Emanuele R. Martin Therapeutic delivery compositions and methods of use thereof
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5371241A (en) 1991-07-19 1994-12-06 Pharmacia P-L Biochemicals Inc. Fluorescein labelled phosphoramidites
US5599797A (en) 1991-10-15 1997-02-04 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US6335434B1 (en) 1998-06-16 2002-01-01 Isis Pharmaceuticals, Inc., Nucleosidic and non-nucleosidic folate conjugates
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
US6235887B1 (en) 1991-11-26 2001-05-22 Isis Pharmaceuticals, Inc. Enhanced triple-helix and double-helix formation directed by oligonucleotides containing modified pyrimidines
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
US5595726A (en) 1992-01-21 1997-01-21 Pharmacyclics, Inc. Chromophore probe for detection of nucleic acid
US5565552A (en) 1992-01-21 1996-10-15 Pharmacyclics, Inc. Method of expanded porphyrin-oligonucleotide conjugate synthesis
EP0642589A4 (en) 1992-05-11 1997-05-21 Ribozyme Pharm Inc METHOD AND REAGENT TO INHIBIT VIRAL REPLICATION.
FR2692265B1 (fr) 1992-05-25 1996-11-08 Centre Nat Rech Scient Composes biologiquement actifs de type phosphotriesters.
US6172208B1 (en) 1992-07-06 2001-01-09 Genzyme Corporation Oligonucleotides modified with conjugate groups
US5272250A (en) 1992-07-10 1993-12-21 Spielvogel Bernard F Boronated phosphoramidate compounds
EP0786522A2 (en) 1992-07-17 1997-07-30 Ribozyme Pharmaceuticals, Inc. Enzymatic RNA molecules for treatment of stenotic conditions
US5721138A (en) 1992-12-15 1998-02-24 Sandford University Apolipoprotein(A) promoter and regulatory sequence constructs and methods of use
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
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
FR2705099B1 (fr) 1993-05-12 1995-08-04 Centre Nat Rech Scient Oligonucléotides phosphorothioates triesters et procédé de préparation.
US5571902A (en) 1993-07-29 1996-11-05 Isis Pharmaceuticals, Inc. Synthesis of oligonucleotides
ATE247128T1 (de) 1993-09-03 2003-08-15 Isis Pharmaceuticals Inc Aminoderivatisierte nukleoside und oligonukleoside
US5519134A (en) 1994-01-11 1996-05-21 Isis Pharmaceuticals, Inc. Pyrrolidine-containing monomers and oligomers
US5539083A (en) 1994-02-23 1996-07-23 Isis Pharmaceuticals, Inc. Peptide nucleic acid combinatorial libraries and improved methods of synthesis
IL112920A (en) 1994-03-07 2003-04-10 Dow Chemical Co Composition comprising a dendritic polymer complexed with at least one unit of biological response modifier and a process for the preparation thereof
US5554746A (en) 1994-05-16 1996-09-10 Isis Pharmaceuticals, Inc. Lactam nucleic acids
US5597696A (en) 1994-07-18 1997-01-28 Becton Dickinson And Company Covalent cyanine dye oligonucleotide conjugates
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
US5801155A (en) 1995-04-03 1998-09-01 Epoch Pharmaceuticals, Inc. Covalently linked oligonucleotide minor grove binder conjugates
US5672662A (en) 1995-07-07 1997-09-30 Shearwater Polymers, Inc. Poly(ethylene glycol) and related polymers monosubstituted with propionic or butanoic acids and functional derivatives thereof for biotechnical applications
US6444806B1 (en) 1996-04-30 2002-09-03 Hisamitsu Pharmaceutical Co., Inc. Conjugates and methods of forming conjugates of oligonucleotides and carbohydrates
US6300319B1 (en) 1998-06-16 2001-10-09 Isis Pharmaceuticals, Inc. Targeted oligonucleotide conjugates
US6335437B1 (en) 1998-09-07 2002-01-01 Isis Pharmaceuticals, Inc. Methods for the preparation of conjugated oligomers
DE19956568A1 (de) 1999-01-30 2000-08-17 Roland Kreutzer Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens
US20030083273A1 (en) * 1999-04-20 2003-05-01 Tod M. Woolf Antisense oligomers
US6395437B1 (en) 1999-10-29 2002-05-28 Advanced Micro Devices, Inc. Junction profiling using a scanning voltage micrograph
US6287860B1 (en) 2000-01-20 2001-09-11 Isis Pharmaceuticals, Inc. Antisense inhibition of MEKK2 expression
GB0001309D0 (en) 2000-01-20 2000-03-08 Nestle Sa Valve arrangement
ES2336887T5 (es) 2000-03-30 2019-03-06 Whitehead Inst Biomedical Res Mediadores de interferencia por ARN específicos de secuencias de ARN
US6559279B1 (en) 2000-09-08 2003-05-06 Isis Pharmaceuticals, Inc. Process for preparing peptide derivatized oligomeric compounds
CA2429814C (en) 2000-12-01 2014-02-18 Thomas Tuschl Rna interference mediating small rna molecules
JP4638225B2 (ja) * 2002-05-30 2011-02-23 ザ スクリプス リサーチ インスティテュート 銅を触媒とするアジドとアセチレンのライゲーション
US8431558B2 (en) 2004-11-01 2013-04-30 The Regents Of The University Of California Compositions and methods for modification of biomolecules
US20060147963A1 (en) * 2004-12-30 2006-07-06 Affymetrix, Inc. Detection of polynucleotides on nucleic acid arrays using azido-modified triphosphate nucleotide analogs
EP1875240A2 (en) * 2005-04-27 2008-01-09 Siemens Medical Solutions USA, Inc. The preparation of molecular imaging probes using click chemistry
EP2270228B1 (en) * 2005-05-02 2013-08-21 baseclick GmbH New labelling strategies for the sensitive detection of analytes
EP1888529A2 (en) * 2005-05-18 2008-02-20 Wyeth 3-cyanoquinoline inhibitors of tpl2 kinase and methods of making and using the same
WO2007081031A1 (ja) * 2006-01-16 2007-07-19 Hokkaido University 糖転移酵素阻害剤
WO2007095387A2 (en) 2006-02-17 2007-08-23 Dharmacon, Inc. Compositions and methods for inhibiting gene silencing by rna interference
EP2021351A2 (en) * 2006-04-28 2009-02-11 Centre National de la Recherche Scientifique Method for the synthesis of triazole-containing oligonucleotide derivatives
AU2007299705B2 (en) 2006-09-22 2012-09-06 Dharmacon, Inc. Duplex oligonucleotide complexes and methods for gene silencing by RNA interference
ATE515488T1 (de) 2006-10-31 2011-07-15 Baseclick Gmbh Click-chemie zur herstellung von reportermolekülen
EP2112928A4 (en) * 2007-02-22 2014-01-08 Univ Utah Res Found SYNTHESIS OF NOVEL XYLOSIDES AND ITS POSSIBLE USES
EP2222341B1 (en) 2007-11-21 2015-02-25 University Of Georgia Research Foundation, Inc. Alkynes and methods of reacting alkynes with 1,3-dipole-functional compounds
CN101497638B (zh) * 2008-01-30 2012-09-26 中国科学院大连化学物理研究所 一种nad+类似物及其合成和应用
AU2009298802A1 (en) * 2008-09-23 2010-04-08 Alnylam Pharmaceuticals, Inc. Chemical modifications of monomers and oligonucleotides with cycloaddition
DE102009039097B3 (de) 2009-08-27 2010-11-25 Siemens Aktiengesellschaft Verfahren zum Übertragen von Daten in einem Sensornetzwerk, Sensorknoten und Zentral-Rechner
WO2012005769A1 (en) 2010-07-09 2012-01-12 Telecommunication Systems, Inc. Location privacy selector
EP3061398B1 (en) 2013-10-21 2020-09-23 Canon Kabushiki Kaisha Radiographic imaging device and method for controlling same, radiographic image processing device and method, and program and computer-readable storage medium
EP3921593B1 (en) 2019-02-04 2023-03-15 Detnet South Africa (Pty) Ltd Boost pump
KR102318555B1 (ko) 2020-03-19 2021-10-29 한국과학기술연구원 광소자용 역나노콘과 그 제조방법

Also Published As

Publication number Publication date
CA2737661C (en) 2019-08-20
CA2737661A1 (en) 2010-05-08
WO2010039548A3 (en) 2012-10-04
JP2019073553A (ja) 2019-05-16
JP2017048242A (ja) 2017-03-09
JP6885976B2 (ja) 2021-06-16
AU2016202354B2 (en) 2017-11-16
JP2012513953A (ja) 2012-06-21
EP2342616A2 (en) 2011-07-13
WO2010039548A2 (en) 2010-04-08
US8962580B2 (en) 2015-02-24
JP6053735B2 (ja) 2016-12-27
US20190048344A1 (en) 2019-02-14
AU2009298802A2 (en) 2011-04-14
JP2014240428A (ja) 2014-12-25
US20120035115A1 (en) 2012-02-09
US20150203847A1 (en) 2015-07-23
AU2016202354A1 (en) 2016-05-05
EP3587434A1 (en) 2020-01-01
JP6484602B2 (ja) 2019-03-13

Similar Documents

Publication Publication Date Title
AU2016202354B2 (en) Chemical modifications of monomers and oligonucleotides with cycloaddition
US10550386B2 (en) Monomers and oligonucleotides comprising cycloaddition adduct(s)
CA2708171C (en) Folate conjugates
JP7296916B2 (ja) オリゴヌクレオチド-リガンドコンジュゲートおよびそれらの調製方法
JP2024020209A (ja) 修飾二本鎖rna剤
JP2013541334A (ja) 修飾されたiRNA剤
AU2009288078A1 (en) Synthetic methods and derivatives of triphosphate oligonucleotides
WO2011094580A2 (en) Chelated copper for use in the preparation of conjugated oligonucleotides

Legal Events

Date Code Title Description
DA3 Amendments made section 104

Free format text: THE NATURE OF THE AMENDMENT IS AS SHOWN IN THE STATEMENT(S) FILED 25 MAR 2011

MK5 Application lapsed section 142(2)(e) - patent request and compl. specification not accepted