CA2737661C - Chemical modifications of monomers and oligonucleotides with cycloaddition - Google Patents

Chemical modifications of monomers and oligonucleotides with cycloaddition Download PDF

Info

Publication number
CA2737661C
CA2737661C CA2737661A CA2737661A CA2737661C CA 2737661 C CA2737661 C CA 2737661C CA 2737661 A CA2737661 A CA 2737661A CA 2737661 A CA2737661 A CA 2737661A CA 2737661 C CA2737661 C CA 2737661C
Authority
CA
Canada
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.)
Active
Application number
CA2737661A
Other languages
English (en)
French (fr)
Other versions
CA2737661A1 (en
Inventor
Muthia Manoharan
Kallanthottathil G. Rajeev
Takeshi Yamada
David Butler
K. Narayanannair Jayaprakash
Muthusamy Jayraman
Shigeo Matsuda
Rajendra K. Pandey
Chang Geng Peng
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 CA2737661A1 publication Critical patent/CA2737661A1/en
Application granted granted Critical
Publication of CA2737661C publication Critical patent/CA2737661C/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04L—TRANSMISSION OF DIGITAL INFORMATION, e.g. TELEGRAPHIC COMMUNICATION
    • H04L65/00—Network arrangements, protocols or services for supporting real-time applications in data packet communication
    • H04L65/60—Network streaming of media packets
    • H04L65/75—Media network packet handling
    • H04L65/762—Media network packet handling at the source 
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04L—TRANSMISSION OF DIGITAL INFORMATION, e.g. TELEGRAPHIC COMMUNICATION
    • H04L67/00—Network arrangements or protocols for supporting network services or applications
    • H04L67/50—Network services
    • H04L67/75—Indicating network or usage conditions on the user display
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/543—Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
    • A61K47/544—Phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
    • C12N2310/141—MicroRNAs, miRNAs
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3513—Protein; Peptide
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol
    • Y—GENERAL 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
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against 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)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (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)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Signal Processing (AREA)
  • Computer Networks & Wireless Communication (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Psychiatry (AREA)
  • Transplantation (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Pulmonology (AREA)
CA2737661A 2008-09-23 2009-09-23 Chemical modifications of monomers and oligonucleotides with cycloaddition Active CA2737661C (en)

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

Publications (2)

Publication Number Publication Date
CA2737661A1 CA2737661A1 (en) 2010-05-08
CA2737661C true CA2737661C (en) 2019-08-20

Family

ID=42038746

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2737661A Active CA2737661C (en) 2008-09-23 2009-09-23 Chemical modifications of monomers and oligonucleotides with cycloaddition

Country Status (6)

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

Families Citing this family (142)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8962580B2 (en) * 2008-09-23 2015-02-24 Alnylam Pharmaceuticals, Inc. Chemical modifications of monomers and oligonucleotides with cycloaddition
US8604184B2 (en) * 2009-05-05 2013-12-10 The United States Of America As Represented By The Secretary Of The Air Force Chemically programmable immunity
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
EP2526113B1 (en) 2010-01-22 2016-08-10 Sirna Therapeutics, Inc. Post-synthetic chemical modification of rna at the 2'-position of the ribose ring via "click" chemistry
WO2011100131A2 (en) 2010-01-28 2011-08-18 Alnylam Pharmacuticals, Inc. Monomers and oligonucleotides comprising cycloaddition adduct(s)
WO2012030683A2 (en) 2010-08-31 2012-03-08 Merck Sharp & Dohme Corp. Novel single chemical entities and methods for delivery of oligonucleotides
WO2012054749A1 (en) 2010-10-20 2012-04-26 Li-Cor, Inc. Cyanine dyes and their conjugates
EP3640332A1 (en) 2011-08-29 2020-04-22 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
EP2755983B1 (en) 2011-09-12 2017-03-15 Idenix Pharmaceuticals LLC. Substituted carbonyloxymethylphosphoramidate compounds and pharmaceutical compositions for the treatment of viral infections
CN103906745B (zh) 2011-09-30 2017-08-25 塔夫斯大学 用于治疗神经变性疾病的尿苷二磷酸衍生物、组合物和方法
IL284530B (en) * 2011-11-18 2022-07-01 Alnylam Pharmaceuticals Inc rnai factors, preparations and methods of using them for the treatment of transthyretin-related diseases
PL2794627T3 (pl) 2011-12-22 2019-04-30 Alios Biopharma Inc Podstawione nukleozydy, nukleotydy i ich analogi
AU2013221448B2 (en) * 2012-02-16 2017-02-23 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
US9254311B2 (en) 2012-04-02 2016-02-09 Moderna Therapeutics, Inc. Modified polynucleotides for the production of proteins
WO2013151663A1 (en) 2012-04-02 2013-10-10 modeRNA Therapeutics Modified polynucleotides for the production of membrane proteins
US9283287B2 (en) 2012-04-02 2016-03-15 Moderna Therapeutics, Inc. Modified polynucleotides for the production of nuclear proteins
US10501513B2 (en) 2012-04-02 2019-12-10 Modernatx, Inc. Modified polynucleotides for the production of oncology-related proteins and peptides
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
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
WO2013177195A1 (en) 2012-05-22 2013-11-28 Idenix Pharmaceuticals, Inc. 3',5'-cyclic phosphate prodrugs for hcv infection
EA027929B1 (ru) 2012-05-25 2017-09-29 Янссен Сайенсиз Айрлэнд Юси Нуклеозиды на основе урацила и спирооксетана
US9192621B2 (en) 2012-09-27 2015-11-24 Idenix Pharmaceuticals Llc Esters and malonates of SATE prodrugs
WO2014052896A1 (en) * 2012-09-28 2014-04-03 Tufts University Uridine diphosphate derivatives, prodrugs, compositions and uses thereof
HK1207647A1 (en) 2012-10-08 2016-02-05 Idenix Pharmaceuticals Llc 2'-chloro nucleoside analogs for hcv infection
WO2014099941A1 (en) 2012-12-19 2014-06-26 Idenix Pharmaceuticals, Inc. 4'-fluoro nucleosides for the treatment of hcv
AU2013361605A1 (en) * 2012-12-20 2015-06-04 Sirna Therapeutics, Inc. Post-synthetic orthogonal amidation plus metal catalyzed azide-alkyne cycloaddition click chemistry on siRNA
WO2014137926A1 (en) 2013-03-04 2014-09-12 Idenix Pharmaceuticals, Inc. 3'-deoxy nucleosides for the treatment of hcv
US9339541B2 (en) 2013-03-04 2016-05-17 Merck Sharp & Dohme Corp. Thiophosphate nucleosides for the treatment of HCV
US10138265B2 (en) 2013-03-13 2018-11-27 Tufts University Uridine nucleoside derivatives, compositions and methods of use
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
CA2904180C (en) 2013-03-13 2022-05-10 Tufts University Uridine nucleoside derivatives, compositions and methods of use
WO2014165542A1 (en) 2013-04-01 2014-10-09 Idenix Pharmaceuticals, Inc. 2',4'-fluoro nucleosides for the treatment of hcv
KR102138781B1 (ko) 2013-05-01 2020-07-28 아이오니스 파마수티컬즈, 인코포레이티드 아포지질단백질 c-iii 발현을 조절하는 조성물 및 방법
EP3004130B1 (en) 2013-06-05 2019-08-07 Idenix Pharmaceuticals LLC. 1',4'-thio nucleosides for the treatment of hcv
BR112015032902A8 (pt) 2013-07-02 2019-12-24 Millennium Pharm Inc compostos de heteroarila, seus usos e composições farmacêuticas
EP3027636B1 (en) 2013-08-01 2022-01-05 Idenix Pharmaceuticals LLC 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
WO2015161137A1 (en) 2014-04-16 2015-10-22 Idenix Pharmaceuticals, Inc. 3'-substituted methyl or alkynyl nucleosides for the treatment of hcv
EP3137476B1 (en) 2014-04-28 2019-10-09 Ionis Pharmaceuticals, Inc. Linkage modified oligomeric compounds
US9994855B2 (en) 2014-05-01 2018-06-12 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating growth hormone receptor expression
PT3137596T (pt) 2014-05-01 2019-09-27 Ionis Pharmaceuticals Inc Composições e métodos para modulação da expressão do factor b do complemento
DK3137091T3 (da) 2014-05-01 2021-01-25 Ionis Pharmaceuticals Inc Konjugater af modificerede antisense-oligonukleotider og anvendelse deraf til modulation af pkk-ekspression
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
CN106460232B (zh) * 2014-05-23 2019-12-24 生捷科技控股公司 用于原位合成的探针阵列的寡核苷酸探针倒转方法
HRP20191979T1 (hr) 2014-07-01 2020-02-07 Millennium Pharmaceuticals, Inc. Heteoarilni spojevi koji su korisni kao inhibitori sumo-aktivirajućeg enzima
WO2016030863A1 (en) * 2014-08-29 2016-03-03 Glaxosmithkline Intellectual Property Development Limited Compounds and methods for treating viral infections
WO2016040748A1 (en) 2014-09-12 2016-03-17 Ionis Pharmaceuticals, Inc. Compositions and methods for detection of smn protein in a subject and treatment of a subject
WO2016100401A1 (en) * 2014-12-15 2016-06-23 Dicerna Pharmaceuticals, Inc. Ligand-modified double-stranded nucleic acids
WO2016152980A1 (ja) * 2015-03-24 2016-09-29 国立大学法人岐阜大学 オリゴヌクレオチド誘導体及びそれを用いたオリゴヌクレオチド構築物並びにそれらの製造方法
CN109477106B (zh) 2015-07-10 2022-10-04 Ionis制药公司 二酰基甘油酰基转移酶2(dgat2)的调节剂
US10695735B2 (en) * 2015-08-18 2020-06-30 Centrillion Technology Holdings Corporation Probe inversion process for in situ synthesized probe arrays
EP3133171B1 (en) * 2015-08-18 2018-10-17 Centrillion Technology Holdings Corporation Probe inversion process for in situ synthesized probe arrays
TWI791251B (zh) 2015-08-26 2023-02-01 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
RU2018113709A (ru) 2015-09-24 2019-10-30 Айонис Фармасьютикалз, Инк. Модуляторы экспрессии kras
LT4119569T (lt) 2015-11-06 2024-09-25 Ionis Pharmaceuticals, Inc. Konjuguoti priešprasmiai junginiai, skirti panaudoti terapijoje
KR20250078597A (ko) 2015-11-06 2025-06-02 아이오니스 파마수티컬즈, 인코포레이티드 아포리포프로테인 (a) 발현 조정
JOP20170057B1 (ar) 2016-03-07 2022-03-14 Arrowhead Pharmaceuticals Inc مركبات ترابطية مستهدفة كمركبات علاجية
ES2891320T3 (es) 2016-03-10 2022-01-27 Janssen Pharmaceutica Nv Análogos de nucleósidos sustituidos para su uso como inhibidores de PRMT5
CN109153697A (zh) * 2016-04-14 2019-01-04 豪夫迈·罗氏有限公司 三苯甲基-单-GalNAc化合物及其用途
WO2018013525A1 (en) 2016-07-11 2018-01-18 Translate Bio Ma, Inc. Nucleic acid conjugates and uses thereof
PL3484524T3 (pl) 2016-07-15 2023-03-20 Ionis Pharmaceuticals, Inc. Związki i sposoby modulacji smn2
IL291323B2 (en) 2016-07-15 2023-09-01 Am Chemicals Llc Solid non-nucleoside supports and phosphoramidite building blocks for oligonucleotide synthesis
WO2018035380A1 (en) 2016-08-17 2018-02-22 Solstice Biologics, Ltd. Polynucleotide constructs
IL300869A (en) 2016-09-02 2023-04-01 Arrowhead Pharmaceuticals Inc Ligands containing a targeting factor, preparations containing them and their uses
KR102531344B1 (ko) 2016-10-03 2023-05-10 얀센 파마슈티카 엔.브이. Prmt5 억제제로서 사용하기 위한 신규의 모노사이클릭 및 바이사이클릭 고리 시스템 치환된 카르바뉴클레오시드 유사체
US11400161B2 (en) 2016-10-06 2022-08-02 Ionis Pharmaceuticals, Inc. Method of conjugating oligomeric compounds
WO2018086139A1 (en) 2016-11-14 2018-05-17 Hangzhou Dac Biotech Co., Ltd Conjugation linkers, cell binding molecule-drug conjugates containing the likers, methods of making and uses such conjugates with the linkers
JP7225106B2 (ja) 2017-02-27 2023-02-20 ヤンセン ファーマシューティカ エヌ．ベー． Ｐｒｍｔ５阻害剤による治療に応答する癌患者の同定におけるバイオマーカーの使用
JOP20190215A1 (ar) 2017-03-24 2019-09-19 Ionis Pharmaceuticals Inc مُعدّلات التعبير الوراثي عن pcsk9
EP4219713A3 (en) 2017-04-05 2023-08-16 Silence Therapeutics GmbH Products and compositions
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
JP2020518578A (ja) 2017-05-01 2020-06-25 ギリアード サイエンシーズ， インコーポレイテッド （Ｓ）−２−エチルブチル２−（（（Ｓ）−（（（２Ｒ，３Ｓ，４Ｒ，５Ｒ）−５−（４−アミノピロロ［２，１−ｆ］［１，２，４］トリアジン−７−イル）−５−シアノ−３，４−ジヒドロキシテトラヒドロフラン−２−イル）メトキシ）（フェノキシ）ホスホリル）アミノ）プロパノエートの結晶形態
US11597744B2 (en) 2017-06-30 2023-03-07 Sirius Therapeutics, Inc. Chiral phosphoramidite auxiliaries and methods of their use
CA3077489A1 (en) 2017-07-11 2019-01-17 Gilead Sciences, Inc. Compositions comprising an rna polymerase inhibitor and cyclodextrin for treating viral infections
JP7352544B2 (ja) 2017-12-08 2023-09-28 ヤンセン ファーマシューティカ エヌ．ベー． 新規なスピロ二環式類似体
WO2019140102A1 (en) 2018-01-10 2019-07-18 Translate Bio Ma, Inc. Compositions and methods for facilitating delivery of synthetic nucleic acids to cells
JP2021511072A (ja) 2018-01-15 2021-05-06 アイオニス・ファーマシューティカルズ・インコーポレイテッドＩｏｎｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． Ｄｎｍ２発現のモジュレーター
WO2019157531A1 (en) 2018-02-12 2019-08-15 Ionis Pharmaceuticals, Inc. Modified compounds and uses thereof
CN119633010A (zh) * 2018-03-07 2025-03-18 埃默里大学 含4′-卤素的核苷酸和核苷治疗组合物以及其相关用途
TW202016301A (zh) 2018-05-07 2020-05-01 美商阿里拉姆製藥股份有限公司 肝外遞送技術
CR20200605A (es) 2018-05-09 2021-01-29 Ionis Pharmaceuticals Inc Compuestos y métodos para la reducción de la expresión de fxi
EP3823725A4 (en) 2018-07-17 2023-05-10 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
TWI856973B (zh) 2018-09-19 2024-10-01 美商Ionis製藥公司 Pnpla3表現之調節劑
PE20211755A1 (es) 2018-12-21 2021-09-07 Ionis Pharmaceuticals Inc Moduladores de la expresion de hsd17b13
EP3902813A4 (en) * 2018-12-28 2022-05-04 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
EP4045062A1 (en) 2019-10-14 2022-08-24 Astrazeneca AB Modulators of pnpla3 expression
WO2021119019A1 (en) 2019-12-09 2021-06-17 Empirico Inc. Oligonucleotides for treatment of angiopoietin like 4 (angptl4) related diseases
CN118766947A (zh) 2020-01-27 2024-10-15 吉利德科学公司 用于治疗SARS CoV-2感染的方法
TWI794742B (zh) 2020-02-18 2023-03-01 美商基利科學股份有限公司 抗病毒化合物
EP4644394A2 (en) 2020-02-18 2025-11-05 Gilead Sciences, Inc. Antiviral compounds
TWI874791B (zh) 2020-02-18 2025-03-01 美商基利科學股份有限公司 抗病毒化合物
AU2021225957A1 (en) 2020-02-28 2022-09-08 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating SMN2
TWI890963B (zh) 2020-03-12 2025-07-21 美商基利科學股份有限公司 1'-氰基核苷之製備方法
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
CN115362004A (zh) 2020-04-06 2022-11-18 吉利德科学公司 1’-氰基取代的碳核苷类似物的吸入制剂
EP4133076A1 (en) * 2020-04-07 2023-02-15 Alnylam Pharmaceuticals, Inc. Angiotensin-converting enzyme 2 (ace2) irna compositions and methods of use thereof
WO2021206922A1 (en) * 2020-04-07 2021-10-14 Alnylam Pharmaceuticals, Inc. Transmembrane serine protease 2 (tmprss2) irna compositions and methods of use thereof
WO2021216785A1 (en) 2020-04-21 2021-10-28 Flagship Pioneering, Inc. Bifunctional molecules and methods of using thereof
ES3041698T3 (en) 2020-05-29 2025-11-13 Gilead Sciences Inc Remdesivir for the treatment of viral infections
JP2023531524A (ja) 2020-06-24 2023-07-24 ギリアード サイエンシーズ， インコーポレイテッド １’－シアノヌクレオシド類似体及びその使用
JP7559223B2 (ja) 2020-08-24 2024-10-01 ギリアード サイエンシーズ， インコーポレイテッド リン脂質化合物及びその使用
IL300453A (en) 2020-08-27 2023-04-01 Gilead Sciences Inc COMPOSITIONS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS
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
WO2022162154A1 (en) * 2021-01-30 2022-08-04 E-Therapeutics Plc Conjugated oligonucleotide compounds, methods of making and uses thereof
WO2022162153A1 (en) * 2021-01-30 2022-08-04 E-Therapeutics Plc Conjugated oligonucleotide compounds, methods of making and uses thereof
KR20230170745A (ko) 2021-04-16 2023-12-19 길리애드 사이언시즈, 인코포레이티드 아미드를 사용한 카르바뉴클레오시드를 제조하는 방법
EP4355756A4 (en) 2021-06-18 2025-08-13 Hongene Biotech Corp N-ACETYLGALACTOSAMINE FUNCTIONALIZED NUCLEOSIDES
JP2024528697A (ja) 2021-07-20 2024-07-30 エイジーエス・セラピューティクス・ソシエテ・パール・アクシオン・サンプリフィエ 微細藻類由来の細胞外小胞、その調製および使用
WO2023023527A1 (en) 2021-08-18 2023-02-23 Gilead Sciences, Inc. Phospholipid compounds and methods of making and using the same
WO2023034719A1 (en) 2021-08-30 2023-03-09 Hongene Biotech Corporation Functionalized n-acetylgalactosamine analogs
US12042509B2 (en) 2021-10-01 2024-07-23 Adarx Pharmaceuticals, Inc. Prekallikrein-modulating compositions and methods of use thereof
CN118401539A (zh) 2021-12-15 2024-07-26 兆维生物科技公司 官能化的n-乙酰半乳糖胺类似物
EP4456893A1 (en) * 2021-12-30 2024-11-06 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
TW202525810A (zh) 2022-03-02 2025-07-01 美商基利科學股份有限公司 用於治療病毒感染的化合物及方法
IL315546A (en) 2022-03-16 2024-11-01 Empirico Inc GALNAC compositions to improve siRNA bioavailability
JP2025512835A (ja) 2022-03-28 2025-04-22 エンピリコ インク． 修飾オリゴヌクレオチド
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
EP4608424A1 (en) 2022-10-24 2025-09-03 AGS Therapeutics SAS Extracellular vesicles from microalgae, their biodistribution upon intranasal administration, and uses thereof
WO2024112877A1 (en) * 2022-11-23 2024-05-30 Eli Lilly And Company Methods of synthesizing a targeting ligand-conjugated nucleotide phosphoramidite
WO2024118503A1 (en) 2022-11-28 2024-06-06 Hongene Biotech Corporation Functionalized n-acetylgalactosamine analogs
AU2024258561A1 (en) 2023-04-20 2025-10-30 Adarx Pharmaceuticals, Inc. Mapt-modulating compositions and methods of use thereof
WO2024238396A1 (en) 2023-05-12 2024-11-21 Adarx Pharmaceuticals, Inc. Nmda ligand conjugated compounds and uses thereof
AU2024279767A1 (en) 2023-05-26 2025-12-04 Adarx Pharmaceuticals, Inc. Sod1-modulating compositions and methods of use thereof
WO2024263694A1 (en) 2023-06-20 2024-12-26 Adarx Pharmaceuticals, Inc. Lrrk2-modulating compositions and methods of use thereof
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
WO2025038970A1 (en) * 2023-08-17 2025-02-20 Adarx Pharmaceuticals, Inc. Modified oligonucleotides containing multiple oligonucleotides
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
US12357577B1 (en) 2024-02-02 2025-07-15 Gilead Sciences, Inc. Pharmaceutical formulations and uses thereof
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
US5258506A (en) 1984-10-16 1993-11-02 Chiron Corporation Photolabile reagents for incorporation into oligonucleotide chains
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US4828979A (en) 1984-11-08 1989-05-09 Life Technologies, Inc. Nucleotide analogs for nucleic acid labeling and detection
AU5698186A (en) 1985-03-15 1986-10-13 Summerton, J. Polynucleotide assay reagent and method
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
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
WO1995024221A1 (en) 1986-08-18 1995-09-14 The Dow Chemical Company Bioactive and/or targeted dendrimer conjugates
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
US5599923A (en) 1989-03-06 1997-02-04 Board Of Regents, University Of Tx Texaphyrin metal complexes having improved functionalization
US5457183A (en) 1989-03-06 1995-10-10 Board Of Regents, The University Of Texas System Hydroxylated texaphyrins
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
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
JP3056782B2 (ja) 1989-11-03 2000-06-26 ヴァンダービルト ユニバーシティ 標的器官内での遺伝子の発現用医薬組成物
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
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5457191A (en) 1990-01-11 1995-10-10 Isis Pharmaceuticals, Inc. 3-deazapurines
US6153737A (en) 1990-01-11 2000-11-28 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5506351A (en) 1992-07-23 1996-04-09 Isis Pharmaceuticals Process for the preparation of 2'-O-alkyl guanosine and related compounds
US5212295A (en) 1990-01-11 1993-05-18 Isis Pharmaceuticals Monomers for preparation of oligonucleotides having chiral phosphorus linkages
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
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
WO1991013080A1 (en) 1990-02-20 1991-09-05 Gilead Sciences, Inc. Pseudonucleosides and pseudonucleotides and their polymers
US5214136A (en) 1990-02-20 1993-05-25 Gilead Sciences, Inc. Anthraquinone-derivatives oligonucleotides
DK0455905T3 (da) 1990-05-11 1998-12-07 Microprobe Corp Dipsticks til nukleinsyrehybridiseringsassays og fremgangsmåde til kovalent immobilisering af oligonukleotider
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
US5386023A (en) 1990-07-27 1995-01-31 Isis Pharmaceuticals Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
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
US5223618A (en) 1990-08-13 1993-06-29 Isis Pharmaceuticals, Inc. 4'-desmethyl nucleoside analog compounds
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5378825A (en) 1990-07-27 1995-01-03 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs
US5614617A (en) 1990-07-27 1997-03-25 Isis Pharmaceuticals, Inc. Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression
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
ATE198598T1 (de) 1990-11-08 2001-01-15 Hybridon Inc Verbindung von mehrfachreportergruppen auf synthetischen oligonukleotiden
US20020123476A1 (en) 1991-03-19 2002-09-05 Emanuele R. Martin Therapeutic delivery compositions and methods of use thereof
US6933286B2 (en) 1991-03-19 2005-08-23 R. Martin Emanuele 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
US5565552A (en) 1992-01-21 1996-10-15 Pharmacyclics, Inc. Method of expanded porphyrin-oligonucleotide conjugate synthesis
US5595726A (en) 1992-01-21 1997-01-21 Pharmacyclics, Inc. Chromophore probe for detection of nucleic acid
WO1993023569A1 (en) 1992-05-11 1993-11-25 Ribozyme Pharmaceuticals, Inc. Method and reagent for inhibiting 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
JPH07509133A (ja) 1992-07-17 1995-10-12 リボザイム・ファーマシューティカルズ・インコーポレイテッド 動物疾患の処置のための方法および剤
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
US5721138A (en) 1992-12-15 1998-02-24 Sandford University Apolipoprotein(A) promoter and regulatory sequence constructs and methods of use
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
DE69433036T2 (de) 1993-09-03 2004-05-27 Isis Pharmaceuticals, Inc., Carlsbad 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
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
AU2001249622B2 (en) 2000-03-30 2007-06-07 Massachusetts Institute Of Technology RNA sequence-specific mediators of RNA interference
US6559279B1 (en) 2000-09-08 2003-05-06 Isis Pharmaceuticals, Inc. Process for preparing peptide derivatized oligomeric compounds
EP1873259B1 (en) 2000-12-01 2012-01-25 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. RNA interference mediated by 21 and 22nt RNAs
ES2346646T5 (es) * 2002-05-30 2018-02-15 The Scripps Research Institute Ligación catalizada con cobre de azidas y acetilenos
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
WO2006116629A2 (en) 2005-04-27 2006-11-02 Siemens Medical Solutions Usa, Inc. The preparation of molecular imaging probes using click chemistry
EP2256126B1 (en) * 2005-05-02 2015-07-01 baseclick GmbH New labelling strategies for the sensitive detection of analytes
JP2008540656A (ja) * 2005-05-18 2008-11-20 ワイス Ｔｐｌ２キナーゼの３−シアノキノリン阻害物質ならびにそれを製造および使用する方法
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
JP2009535323A (ja) * 2006-04-28 2009-10-01 サントル ナショナル ドゥ ラ ルシェルシュ シアンティフィク オリゴヌクレオチド誘導体を合成する方法
US8252755B2 (en) 2006-09-22 2012-08-28 Dharmacon, Inc. Duplex oligonucleotide complexes and methods for gene silencing by RNA interference
HRP20110554T1 (hr) * 2006-10-31 2011-09-30 Baseclick Gmbh "klik" kemija za proizvodnju reporter molekula
EP2112928A4 (en) * 2007-02-22 2014-01-08 Univ Utah Res Found SYNTHESIS OF NOVEL XYLOSIDES AND ITS POSSIBLE USES
CN104529711B (zh) 2007-11-21 2020-02-07 乔治亚大学研究基金公司 炔烃以及炔烃与1,3-偶极-官能化合物反应的方法
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
US8962580B2 (en) * 2008-09-23 2015-02-24 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
US8315599B2 (en) 2010-07-09 2012-11-20 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
AU2020219440A1 (en) 2019-02-04 2021-08-19 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
AU2009298802A1 (en) 2010-04-08
WO2010039548A2 (en) 2010-04-08
EP3587434A1 (en) 2020-01-01
AU2016202354A1 (en) 2016-05-05
US20120035115A1 (en) 2012-02-09
CA2737661A1 (en) 2010-05-08
JP2012513953A (ja) 2012-06-21
US20190048344A1 (en) 2019-02-14
WO2010039548A3 (en) 2012-10-04
JP6053735B2 (ja) 2016-12-27
US20150203847A1 (en) 2015-07-23
AU2016202354B2 (en) 2017-11-16
JP6885976B2 (ja) 2021-06-16
EP2342616A2 (en) 2011-07-13
JP2014240428A (ja) 2014-12-25
JP2019073553A (ja) 2019-05-16
JP6484602B2 (ja) 2019-03-13
US8962580B2 (en) 2015-02-24
JP2017048242A (ja) 2017-03-09
AU2009298802A2 (en) 2011-04-14

Similar Documents

Publication Publication Date Title
CA2737661C (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
AU2009234266B2 (en) Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
JP2021073183A (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
AU2017206154A1 (en) Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20140725