SG11201509712YA - SERPINA1 iRNA COMPOSITIONS AND METHODS OF USE THEREOF - Google Patents

SERPINA1 iRNA COMPOSITIONS AND METHODS OF USE THEREOF

Info

Publication number
SG11201509712YA
SG11201509712YA SG11201509712YA SG11201509712YA SG11201509712YA SG 11201509712Y A SG11201509712Y A SG 11201509712YA SG 11201509712Y A SG11201509712Y A SG 11201509712YA SG 11201509712Y A SG11201509712Y A SG 11201509712YA SG 11201509712Y A SG11201509712Y A SG 11201509712YA
Authority
SG
Singapore
Prior art keywords
methods
irna compositions
serpina1
serpina1 irna
compositions
Prior art date
Application number
SG11201509712YA
Other languages
English (en)
Inventor
Alfica Sehgal
Klaus Charisse
Brian Bettencourt
Martin Maier
Kallanthottathil G Rajeev
Gregory Hinkle
Muthiah Manoharan
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 SG11201509712YA publication Critical patent/SG11201509712YA/en

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
    • A61K31/712—Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
    • 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
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C12N2310/331—Universal or degenerate base
    • 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
    • C12N2310/33—Chemical structure of the base
    • C12N2310/332—Abasic residue
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/343—Spatial arrangement of the modifications having patterns, e.g. ==--==--==--
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/344—Position-specific modifications, e.g. on every purine, at the 3'-end
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/32—Special delivery means, e.g. tissue-specific
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/34—Allele or polymorphism specific uses
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/50—Methods for regulating/modulating their activity
    • C12N2320/51—Methods for regulating/modulating their activity modulating the chemical stability, e.g. nuclease-resistance
    • 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
    • C12N2330/00—Production
    • C12N2330/30—Production chemically synthesised

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Epidemiology (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Saccharide Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
SG11201509712YA 2013-05-22 2014-05-22 SERPINA1 iRNA COMPOSITIONS AND METHODS OF USE THEREOF SG11201509712YA (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201361826125P 2013-05-22 2013-05-22
US201361898695P 2013-11-01 2013-11-01
US201461979727P 2014-04-15 2014-04-15
US201461989028P 2014-05-06 2014-05-06
PCT/US2014/039109 WO2014190137A1 (en) 2013-05-22 2014-05-22 SERPINA1 iRNA COMPOSITIONS AND METHODS OF USE THEREOF

Publications (1)

Publication Number Publication Date
SG11201509712YA true SG11201509712YA (en) 2016-01-28

Family

ID=51934144

Family Applications (3)

Application Number Title Priority Date Filing Date
SG10201804472YA SG10201804472YA (en) 2013-05-22 2014-05-22 SERPINA1 iRNA COMPOSITIONS AND METHODS OF USE THEREOF
SG10201913872XA SG10201913872XA (en) 2013-05-22 2014-05-22 SERPINA1 iRNA COMPOSITIONS AND METHODS OF USE THEREOF
SG11201509712YA SG11201509712YA (en) 2013-05-22 2014-05-22 SERPINA1 iRNA COMPOSITIONS AND METHODS OF USE THEREOF

Family Applications Before (2)

Application Number Title Priority Date Filing Date
SG10201804472YA SG10201804472YA (en) 2013-05-22 2014-05-22 SERPINA1 iRNA COMPOSITIONS AND METHODS OF USE THEREOF
SG10201913872XA SG10201913872XA (en) 2013-05-22 2014-05-22 SERPINA1 iRNA COMPOSITIONS AND METHODS OF USE THEREOF

Country Status (33)

Country Link
US (5) US9574192B2 (ko)
EP (2) EP3412774A1 (ko)
JP (3) JP6495250B2 (ko)
KR (3) KR20220154244A (ko)
CN (2) CN105408481B (ko)
AU (2) AU2014268509B2 (ko)
BR (1) BR112015029139B1 (ko)
CA (1) CA2912826A1 (ko)
CL (1) CL2015003441A1 (ko)
CY (1) CY1122159T1 (ko)
DK (1) DK2999785T3 (ko)
DO (1) DOP2015000288A (ko)
EA (1) EA038792B1 (ko)
ES (1) ES2676146T3 (ko)
GT (1) GT201500330A (ko)
HK (1) HK1221979A1 (ko)
HR (1) HRP20181030T1 (ko)
HU (1) HUE038146T2 (ko)
IL (3) IL242637B (ko)
LT (1) LT2999785T (ko)
MX (1) MX2021000656A (ko)
MY (1) MY176712A (ko)
PE (2) PE20160030A1 (ko)
PL (1) PL2999785T3 (ko)
PT (1) PT2999785T (ko)
RS (1) RS57418B1 (ko)
RU (1) RU2015154721A (ko)
SG (3) SG10201804472YA (ko)
SI (1) SI2999785T1 (ko)
TW (2) TWI664187B (ko)
UY (1) UY35582A (ko)
WO (1) WO2014190137A1 (ko)
ZA (1) ZA201509252B (ko)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3366775B1 (en) * 2011-11-18 2022-04-27 Alnylam Pharmaceuticals, Inc. Modified rnai agents
EA038792B1 (ru) 2013-05-22 2021-10-20 Элнилэм Фармасьютикалз, Инк. КОМПОЗИЦИИ НА ОСНОВЕ RNAi Serpina1 И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
US9458457B2 (en) 2013-07-03 2016-10-04 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of alpha-1 antitrypsin by double-stranded RNA
EP3146049B1 (en) 2014-05-22 2020-02-26 Alnylam Pharmaceuticals, Inc. Angiotensinogen (agt) irna compositions and methods of use thereof
TW201620526A (zh) * 2014-06-17 2016-06-16 愛羅海德研究公司 用於抑制α－１抗胰蛋白酶基因表現之組合物及方法
MX2017002144A (es) 2014-08-20 2017-08-15 Alnylam Pharmaceuticals Inc Agentes de ácido ribonucleico (arn) de cadena doble modificados.
AU2015311706A1 (en) 2014-09-07 2017-02-02 Selecta Biosciences, Inc. Methods and compositions for attenuating gene therapy anti-viral transfer vector immune responses
JP6985283B2 (ja) 2015-12-07 2021-12-22 ジェンザイム・コーポレーション Ｓｅｒｐｉｎｃ１関連障害を処置するための方法および組成物
WO2018013912A1 (en) * 2016-07-15 2018-01-18 The Board Of Regents Of The University Of Oklahoma Anti-arid3a treatments for inflammatory disorders
TWI788312B (zh) 2016-11-23 2023-01-01 美商阿尼拉製藥公司 絲胺酸蛋白酶抑制因子Ａ１ ｉＲＮＡ組成物及其使用方法
CA3043768A1 (en) 2016-11-29 2018-06-07 PureTech Health LLC Exosomes for delivery of therapeutic agents
KR20240096846A (ko) 2017-01-10 2024-06-26 애로우헤드 파마슈티컬스 인코포레이티드 알파-1 항트립신 (AAT) RNAi 작용제, AAT RNAi 작용제를 포함하는 조성물, 및 사용 방법
EP3600345A4 (en) 2017-03-29 2021-01-06 Cornell University OXIDATION-RESISTANT AAT GENE THERAPY
EP3694543A1 (en) 2017-10-13 2020-08-19 Selecta Biosciences, Inc. Methods and compositions for attenuating anti-viral transfer vector igm responses
EP3714054A1 (en) * 2017-11-20 2020-09-30 Alnylam Pharmaceuticals, Inc. Serum amyloid p component (apcs) irna compositions and methods of use thereof
CN112313335B (zh) 2018-05-14 2024-07-09 阿尔尼拉姆医药品有限公司 血管紧张素原(AGT)iRNA组合物及其使用方法
WO2020010311A2 (en) * 2018-07-05 2020-01-09 Active Genomes Expressed Diagnostics, Inc Viral oncogene influences and gene expression patterns as indicators of early tumorigenesis
EP3976802A1 (en) 2019-05-28 2022-04-06 Selecta Biosciences, Inc. Methods and compositions for attenuated anti-viral transfer vector immune response
EP4392556A1 (en) * 2021-08-25 2024-07-03 Dicerna Pharmaceuticals, Inc. Compositions and methods for inhibiting ?lpha-1 antitrypsin expression
US20230141563A1 (en) 2021-10-12 2023-05-11 Selecta Biosciences, Inc. Methods and compositions for attenuating anti-viral transfer vector igm responses
WO2023172624A1 (en) 2022-03-09 2023-09-14 Selecta Biosciences, Inc. Immunosuppressants in combination with anti-igm agents and related dosing

Family Cites Families (258)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US564562A (en) 1896-07-21 Joseph p
US513030A (en) 1894-01-16 Machine for waxing or coating paper
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
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
US4476301A (en) 1982-04-29 1984-10-09 Centre National De La Recherche Scientifique Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon
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
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
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
US5550111A (en) 1984-07-11 1996-08-27 Temple University-Of The Commonwealth System Of Higher Education Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof
FR2567892B1 (fr) 1984-07-19 1989-02-17 Centre Nat Rech Scient Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons
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
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with 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
US4897355A (en) 1985-01-07 1990-01-30 Syntex (U.S.A.) Inc. N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor
FR2575751B1 (fr) 1985-01-08 1987-04-03 Pasteur Institut Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US4683202A (en) 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4762779A (en) 1985-06-13 1988-08-09 Amgen Inc. Compositions and methods for functionalizing nucleic acids
US5139941A (en) 1985-10-31 1992-08-18 University Of Florida Research Foundation, Inc. AAV transduction vectors
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
US4837028A (en) 1986-12-24 1989-06-06 Liposome Technology, Inc. Liposomes with enhanced circulation time
US4920016A (en) 1986-12-24 1990-04-24 Linear Technology, Inc. Liposomes with enhanced circulation time
US5264423A (en) 1987-03-25 1993-11-23 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US5276019A (en) 1987-03-25 1994-01-04 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
ATE113059T1 (de) 1987-06-24 1994-11-15 Florey Howard Inst Nukleosid-derivate.
US5585481A (en) 1987-09-21 1996-12-17 Gen-Probe Incorporated Linking reagents for nucleotide probes
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
US4924624A (en) 1987-10-22 1990-05-15 Temple University-Of The Commonwealth System Of Higher Education 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof
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
EP0406309A4 (en) 1988-03-25 1992-08-19 The University Of Virginia Alumni Patents Foundation Oligonucleotide n-alkylphosphoramidates
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
US5109124A (en) 1988-06-01 1992-04-28 Biogen, Inc. Nucleic acid probe linked to a label having a terminal cysteine
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
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
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
FR2645866B1 (fr) 1989-04-17 1991-07-05 Centre Nat Rech Scient Nouvelles lipopolyamines, leur preparation et leur emploi
US5391723A (en) 1989-05-31 1995-02-21 Neorx Corporation Oligonucleotide conjugates
US4958013A (en) 1989-06-06 1990-09-18 Northwestern University Cholesteryl modified oligonucleotides
US5143854A (en) 1989-06-07 1992-09-01 Affymax Technologies N.V. Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof
US5744101A (en) 1989-06-07 1998-04-28 Affymax Technologies N.V. Photolabile nucleoside protecting groups
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
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
US5436146A (en) 1989-09-07 1995-07-25 The Trustees Of Princeton University Helper-free stocks of recombinant adeno-associated virus vectors
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
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
AU658562B2 (en) 1989-10-24 1995-04-27 Isis Pharmaceuticals, Inc. 2' modified oligonucleotides
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
CA2029273A1 (en) 1989-12-04 1991-06-05 Christine L. Brakel Modified nucleotide compounds
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
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
US6783931B1 (en) 1990-01-11 2004-08-31 Isis Pharmaceuticals, Inc. Amine-derivatized nucleosides and oligonucleosides
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US5852188A (en) 1990-01-11 1998-12-22 Isis Pharmaceuticals, Inc. Oligonucleotides having chiral phosphorus linkages
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US7037646B1 (en) 1990-01-11 2006-05-02 Isis Pharmaceuticals, Inc. Amine-derivatized nucleosides and oligonucleosides
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
AU7579991A (en) 1990-02-20 1991-09-18 Gilead Sciences, Inc. Pseudonucleosides and pseudonucleotides and their polymers
US5214136A (en) 1990-02-20 1993-05-25 Gilead Sciences, Inc. Anthraquinone-derivatives oligonucleotides
US5321131A (en) 1990-03-08 1994-06-14 Hybridon, Inc. Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling
US5470967A (en) 1990-04-10 1995-11-28 The Dupont Merck Pharmaceutical Company Oligonucleotide analogs with sulfamate linkages
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
GB9009980D0 (en) 1990-05-03 1990-06-27 Amersham Int Plc Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides
DE69032425T2 (de) 1990-05-11 1998-11-26 Microprobe Corp., Bothell, Wash. Teststreifen zum Eintauchen für Nukleinsäure-Hybridisierungsassays und Verfahren zur kovalenten Immobilisierung von Oligonucleotiden
US5981276A (en) 1990-06-20 1999-11-09 Dana-Farber Cancer Institute Vectors containing HIV packaging sequences, packaging defective HIV vectors, and uses thereof
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5688941A (en) 1990-07-27 1997-11-18 Isis Pharmaceuticals, Inc. Methods of making conjugated 4' desmethyl nucleoside analog compounds
DE69126530T2 (de) 1990-07-27 1998-02-05 Isis Pharmaceutical, Inc., Carlsbad, Calif. Nuklease resistente, pyrimidin modifizierte oligonukleotide, die die gen-expression detektieren und modulieren
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5245022A (en) 1990-08-03 1993-09-14 Sterling Drug, Inc. Exonuclease resistant terminally substituted oligonucleotides
NZ239247A (en) 1990-08-03 1993-11-25 Sterling Drug Inc Oligonucleosides containing a non-phosphate inter nucleoside linkage
US5512667A (en) 1990-08-28 1996-04-30 Reed; Michael W. Trifunctional intermediates for preparing 3'-tailed oligonucleotides
US5214134A (en) 1990-09-12 1993-05-25 Sterling Winthrop Inc. Process of linking nucleosides with a siloxane bridge
US5561225A (en) 1990-09-19 1996-10-01 Southern Research Institute Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages
EP0549686A4 (en) 1990-09-20 1995-01-18 Gilead Sciences Inc Modified internucleoside linkages
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
EP0556301B1 (en) 1990-11-08 2001-01-10 Hybridon, Inc. Incorporation of multiple reporter groups on synthetic oligonucleotides
GB9100304D0 (en) 1991-01-08 1991-02-20 Ici Plc Compound
US7015315B1 (en) 1991-12-24 2006-03-21 Isis Pharmaceuticals, Inc. Gapped oligonucleotides
US5714331A (en) 1991-05-24 1998-02-03 Buchardt, Deceased; Ole Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5719262A (en) 1993-11-22 1998-02-17 Buchardt, Deceased; Ole Peptide nucleic acids having amino acid side chains
US5371241A (en) 1991-07-19 1994-12-06 Pharmacia P-L Biochemicals Inc. Fluorescein labelled phosphoramidites
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
US5283185A (en) 1991-08-28 1994-02-01 University Of Tennessee Research Corporation Method for delivering nucleic acids into cells
DE59208572D1 (de) 1991-10-17 1997-07-10 Ciba Geigy Ag Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte
US5594121A (en) 1991-11-07 1997-01-14 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified purines
US5252479A (en) 1991-11-08 1993-10-12 Research Corporation Technologies, Inc. Safe vector for gene therapy
US5677195A (en) 1991-11-22 1997-10-14 Affymax Technologies N.V. Combinatorial strategies for polymer synthesis
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
ATE515510T1 (de) 1991-12-24 2011-07-15 Isis Pharmaceuticals Inc Durch dna-abschnitte unterbrochene modifizierte oligonukleotide
US6277603B1 (en) 1991-12-24 2001-08-21 Isis Pharmaceuticals, Inc. PNA-DNA-PNA chimeric macromolecules
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
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
DE4203923A1 (de) 1992-02-11 1993-08-12 Henkel Kgaa Verfahren zur herstellung von polycarboxylaten auf polysaccharid-basis
US5633360A (en) 1992-04-14 1997-05-27 Gilead Sciences, Inc. Oligonucleotide analogs capable of passive cell membrane permeation
US5434257A (en) 1992-06-01 1995-07-18 Gilead Sciences, Inc. Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
US5587308A (en) 1992-06-02 1996-12-24 The United States Of America As Represented By The Department Of Health & Human Services Modified adeno-associated virus vector capable of expression from a novel promoter
CA2134773A1 (en) 1992-06-04 1993-12-09 Robert J. Debs Methods and compositions for in vivo gene therapy
AU4541093A (en) 1992-06-18 1994-01-24 Genpharm International, Inc. Methods for producing transgenic non-human animals harboring a yeast artificial chromosome
EP0577558A2 (de) 1992-07-01 1994-01-05 Ciba-Geigy Ag Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte
US5272250A (en) 1992-07-10 1993-12-21 Spielvogel Bernard F Boronated phosphoramidate compounds
AU4769893A (en) 1992-07-17 1994-02-14 Ribozyme Pharmaceuticals, Inc. Method and reagent for treatment of animal diseases
US6346614B1 (en) 1992-07-23 2002-02-12 Hybridon, Inc. Hybrid oligonucleotide phosphorothioates
US5783701A (en) 1992-09-08 1998-07-21 Vertex Pharmaceuticals, Incorporated Sulfonamide inhibitors of aspartyl protease
CA2145641C (en) 1992-12-03 2008-05-27 Richard J. Gregory Pseudo-adenovirus vectors
US5478745A (en) 1992-12-04 1995-12-26 University Of Pittsburgh Recombinant viral vector system
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
RU2123492C1 (ru) 1993-02-19 1998-12-20 Ниппон Синяку Ко., Лтд Производные глицерина, средство для доставки физиологически активного вещества и фармацевтическая композиция
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
ES2107205T3 (es) 1993-03-30 1997-11-16 Sanofi Sa Analogos de nucleosidos aciclicos y secuencias oligonucleotidas que los contienen.
DE69407032T2 (de) 1993-03-31 1998-07-02 Sanofi Sa Oligonucleotide mit amidverkettungen die phosphoesterverkettungen einsetzen
DE4311944A1 (de) 1993-04-10 1994-10-13 Degussa Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen
US6191105B1 (en) 1993-05-10 2001-02-20 Protein Delivery, Inc. Hydrophilic and lipophilic balanced microemulsion formulations of free-form and/or conjugation-stabilized therapeutic agents such as insulin
US5955591A (en) 1993-05-12 1999-09-21 Imbach; Jean-Louis Phosphotriester oligonucleotides, amidites and method of preparation
US6015886A (en) 1993-05-24 2000-01-18 Chemgenes Corporation Oligonucleotide phosphate esters
US6294664B1 (en) 1993-07-29 2001-09-25 Isis Pharmaceuticals, Inc. Synthesis of oligonucleotides
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
CA2176256A1 (en) 1993-11-16 1995-05-26 Lyle John Arnold, Jr. Synthetic oligomers having chirally pure phosphonate internucleosidyl linkages mixed with non-phosphonate internucleosidyl linkages
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
US5446137B1 (en) 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
US5519134A (en) 1994-01-11 1996-05-21 Isis Pharmaceuticals, Inc. Pyrrolidine-containing monomers and oligomers
US5599922A (en) 1994-03-18 1997-02-04 Lynx Therapeutics, Inc. Oligonucleotide N3'-P5' phosphoramidates: hybridization and nuclease resistance properties
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
US5625050A (en) 1994-03-31 1997-04-29 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
US6054299A (en) 1994-04-29 2000-04-25 Conrad; Charles A. Stem-loop cloning vector and method
WO2000022114A1 (en) 1998-10-09 2000-04-20 Ingene, Inc. PRODUCTION OF ssDNA $i(IN VIVO)
US5525711A (en) 1994-05-18 1996-06-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Pteridine nucleotide analogs as fluorescent DNA probes
US5543152A (en) 1994-06-20 1996-08-06 Inex Pharmaceuticals Corporation Sphingosomes for enhanced drug delivery
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
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
US5556752A (en) 1994-10-24 1996-09-17 Affymetrix, Inc. Surface-bound, unimolecular, double-stranded DNA
US6608035B1 (en) 1994-10-25 2003-08-19 Hybridon, Inc. Method of down-regulating gene expression
US5665557A (en) 1994-11-14 1997-09-09 Systemix, Inc. Method of purifying a population of cells enriched for hematopoietic stem cells populations of cells obtained thereby and methods of use thereof
WO1996027606A1 (en) 1995-03-06 1996-09-12 Isis Pharmaceuticals, Inc. Improved process for the synthesis of 2'-o-substituted pyrimidines and oligomeric compounds therefrom
US6166197A (en) 1995-03-06 2000-12-26 Isis Pharmaceuticals, Inc. Oligomeric compounds having pyrimidine nucleotide (S) with 2'and 5 substitutions
CA2220950A1 (en) 1995-05-26 1996-11-28 Somatix Therapy Corporation Delivery vehicles comprising stable lipid/nucleic acid complexes
US5981501A (en) 1995-06-07 1999-11-09 Inex Pharmaceuticals Corp. Methods for encapsulating plasmids in lipid bilayers
US5545531A (en) 1995-06-07 1996-08-13 Affymax Technologies N.V. Methods for making a device for concurrently processing multiple biological chip assays
US7422902B1 (en) 1995-06-07 2008-09-09 The University Of British Columbia Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer
CA2222328C (en) 1995-06-07 2012-01-10 Inex Pharmaceuticals Corporation Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer
US5858397A (en) 1995-10-11 1999-01-12 University Of British Columbia Liposomal formulations of mitoxantrone
WO1997014809A2 (en) 1995-10-16 1997-04-24 Dana-Farber Cancer Institute Novel expression vectors and methods of use
US6160109A (en) 1995-10-20 2000-12-12 Isis Pharmaceuticals, Inc. Preparation of phosphorothioate and boranophosphate oligomers
US5854033A (en) 1995-11-21 1998-12-29 Yale University Rolling circle replication reporter systems
US5858401A (en) 1996-01-22 1999-01-12 Sidmak Laboratories, Inc. Pharmaceutical composition for cyclosporines
US5994316A (en) 1996-02-21 1999-11-30 The Immune Response Corporation Method of preparing polynucleotide-carrier complexes for delivery to cells
US6444423B1 (en) 1996-06-07 2002-09-03 Molecular Dynamics, Inc. Nucleosides comprising polydentate ligands
PT1007533E (pt) * 1996-08-27 2005-09-30 Univ Utah Res Found Bioconjugados e administracao de agentes bioactivos
US6639062B2 (en) 1997-02-14 2003-10-28 Isis Pharmaceuticals, Inc. Aminooxy-modified nucleosidic compounds and oligomeric compounds prepared therefrom
US6576752B1 (en) 1997-02-14 2003-06-10 Isis Pharmaceuticals, Inc. Aminooxy functionalized oligomers
US6172209B1 (en) 1997-02-14 2001-01-09 Isis Pharmaceuticals Inc. Aminooxy-modified oligonucleotides and methods for making same
US6034135A (en) 1997-03-06 2000-03-07 Promega Biosciences, Inc. Dimeric cationic lipids
JP3756313B2 (ja) 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
DE69834038D1 (de) 1997-07-01 2006-05-18 Isis Pharmaceutical Inc Zusammensetzungen und verfahren zur verabreichung von oligonukleotiden über die speiseröhre
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
US6617438B1 (en) 1997-11-05 2003-09-09 Sirna Therapeutics, Inc. Oligoribonucleotides with enzymatic activity
US6528640B1 (en) 1997-11-05 2003-03-04 Ribozyme Pharmaceuticals, Incorporated Synthetic ribonucleic acids with RNAse activity
US6320017B1 (en) 1997-12-23 2001-11-20 Inex Pharmaceuticals Corp. Polyamide oligomers
CN1110492C (zh) 1997-12-24 2003-06-04 沃泰克斯药物股份有限公司 天冬氨酰蛋白酶抑制剂的前药
US6436989B1 (en) 1997-12-24 2002-08-20 Vertex Pharmaceuticals, Incorporated Prodrugs of aspartyl protease inhibitors
US7273933B1 (en) 1998-02-26 2007-09-25 Isis Pharmaceuticals, Inc. Methods for synthesis of oligonucleotides
US7045610B2 (en) 1998-04-03 2006-05-16 Epoch Biosciences, Inc. Modified oligonucleotides for mismatch discrimination
US6531590B1 (en) 1998-04-24 2003-03-11 Isis Pharmaceuticals, Inc. Processes for the synthesis of oligonucleotide compounds
US6867294B1 (en) 1998-07-14 2005-03-15 Isis Pharmaceuticals, Inc. Gapped oligomers having site specific chiral phosphorothioate internucleoside linkages
EP1096921B1 (en) 1998-07-20 2003-04-16 Protiva Biotherapeutics Inc. Liposomal encapsulated nucleic acid-complexes
JP2002527061A (ja) 1998-10-09 2002-08-27 インジーン・インコーポレイテッド ｓｓＤＮＡの酵素的合成
US6465628B1 (en) 1999-02-04 2002-10-15 Isis Pharmaceuticals, Inc. Process for the synthesis of oligomeric compounds
TWI260322B (en) 1999-02-12 2006-08-21 Vertex Pharma Inhibitors of aspartyl protease
AU3243300A (en) 1999-02-23 2000-09-14 Isis Pharmaceuticals, Inc. Multiparticulate formulation
US7084125B2 (en) 1999-03-18 2006-08-01 Exiqon A/S Xylo-LNA analogues
CA2372085C (en) 1999-05-04 2009-10-27 Exiqon A/S L-ribo-lna analogues
US6593466B1 (en) 1999-07-07 2003-07-15 Isis Pharmaceuticals, Inc. Guanidinium functionalized nucleotides and precursors thereof
US6147200A (en) 1999-08-19 2000-11-14 Isis Pharmaceuticals, Inc. 2'-O-acetamido modified monomers and oligomers
WO2001053307A1 (en) 2000-01-21 2001-07-26 Geron Corporation 2'-arabino-fluorooligonucleotide n3'→p5'phosphoramidates: their synthesis and use
IT1318539B1 (it) 2000-05-26 2003-08-27 Italfarmaco Spa Composizioni farmaceutiche a rilascio prolungato per lasomministrazione parenterale di sostanze idrofile biologicamente
EP1334109B1 (en) 2000-10-04 2006-05-10 Santaris Pharma A/S Improved synthesis of purine locked nucleic acid analogues
US7063860B2 (en) 2001-08-13 2006-06-20 University Of Pittsburgh Application of lipid vehicles and use for drug delivery
US20050137153A1 (en) * 2002-02-20 2005-06-23 Sirna Therapeutics, Inc. RNA interference mediated inhibition of alpha-1 antitrypsin (AAT) gene expression using short interfering nucleic acid (siNA)
EP2314690A1 (en) 2002-07-10 2011-04-27 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. RNA-interference by single-stranded RNA molecules
US6878805B2 (en) 2002-08-16 2005-04-12 Isis Pharmaceuticals, Inc. Peptide-conjugated oligomeric compounds
US9839649B2 (en) * 2002-11-14 2017-12-12 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
EP1560931B1 (en) 2002-11-14 2011-07-27 Dharmacon, Inc. Functional and hyperfunctional sirna
WO2006006948A2 (en) 2002-11-14 2006-01-19 Dharmacon, Inc. METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY
WO2005021570A1 (ja) 2003-08-28 2005-03-10 Gene Design, Inc. Ｎ−０結合性架橋構造型新規人工核酸
US8053232B2 (en) 2004-01-23 2011-11-08 Virxsys Corporation Correction of alpha-1-antitrypsin genetic defects using spliceosome mediated RNA trans splicing
CA2554212A1 (en) 2004-02-10 2005-08-25 Sirna Therapeutics, Inc. Rna interference mediated inhibition of gene expression using multifunctional short interfering nucleic acid (multifunctional sina)
WO2005116204A1 (ja) 2004-05-11 2005-12-08 Rnai Co., Ltd. Ｒｎａ干渉を生じさせるポリヌクレオチド、および、これを用いた遺伝子発現抑制方法
EP1802643A1 (en) 2004-10-19 2007-07-04 Replicor Inc. Antiviral oligonucleotides
PL1866414T3 (pl) 2005-03-31 2012-10-31 Calando Pharmaceuticals Inc Inhibitory podjednostki 2 reduktazy rybonukleotydowej i ich zastosowania
ES2516815T3 (es) 2006-01-27 2014-10-31 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos modificados en la posición 6
US8362229B2 (en) 2006-02-08 2013-01-29 Quark Pharmaceuticals, Inc. Tandem siRNAS
CA2648585C (en) 2006-04-07 2017-07-25 Idera Pharmaceuticals, Inc. Stabilized immune modulatory rna (simra) compounds for tlr7 and tlr8
CA2848238C (en) 2006-10-03 2016-07-19 Tekmira Pharmaceuticals Corporation Lipid containing formulations
JP5737937B2 (ja) 2007-07-09 2015-06-17 イデラ ファーマシューティカルズ インコーポレイテッドＩｄｅｒａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 安定化免疫調節ｒｎａ（ｓｉｍｒａ）化合物
CA2708173C (en) * 2007-12-04 2016-02-02 Alnylam Pharmaceuticals, Inc. Targeting lipids
MX2010008394A (es) * 2008-01-31 2010-11-12 Alnylam Pharmaceuticals Inc Metodos optimizados para administracion de arndc focalizando el gen pcsk9.
US20110130440A1 (en) 2008-03-26 2011-06-02 Alnylam Pharmaceuticals, Inc. Non-natural ribonucleotides, and methods of use thereof
HUE034483T2 (en) 2008-04-15 2018-02-28 Protiva Biotherapeutics Inc New lipid preparations for introducing a nucleic acid
EP2341943B1 (en) 2008-09-22 2018-11-07 Dicerna Pharmaceuticals, Inc. Compositions and methods for the specific inhibition of gene expression by dsrna possessing modifications
KR101728655B1 (ko) 2008-12-18 2017-04-19 다이서나 파마수이티컬, 인크. 유전자 발현의 특이적 억제를 위한 연장된 다이서 기질 제제 및 방법
ES2804764T3 (es) 2009-06-01 2021-02-09 Halo Bio Rnai Therapeutics Inc Polinucleótidos para la interferencia de ARN multivalente, composiciones y métodos de uso de los mismos
PL2440183T3 (pl) 2009-06-10 2019-01-31 Arbutus Biopharma Corporation Ulepszona formulacja lipidowa
BRPI1010689A2 (pt) * 2009-06-15 2016-03-15 Alnylam Pharmaceuticals Inc "dsrna formulado por lipídios direcionados para o gene pcsk9"
US9512164B2 (en) 2009-07-07 2016-12-06 Alnylam Pharmaceuticals, Inc. Oligonucleotide end caps
PT2470656E (pt) 2009-08-27 2015-07-16 Idera Pharmaceuticals Inc Composição para inibir expressão de gene e suas utilizações
EP4134433A1 (en) * 2011-06-23 2023-02-15 Alnylam Pharmaceuticals, Inc. Serpina1 sirnas: compositions of matter and methods of treatment
TWI484183B (zh) * 2011-09-01 2015-05-11 Univ Nat Cheng Kung 癌症轉移之評估方法及生物標記、及抑制癌症轉移之ｓｉＲＮＡ化合物
WO2013142514A1 (en) 2012-03-19 2013-09-26 Isis Pharmaceuticals, Inc. Methods and compositions for modulating alpha-1-antitrypsin expression
AU2013262699A1 (en) * 2012-05-16 2015-01-22 Rana Therapeutics, Inc. Compositions and methods for modulating ATP2A2 expression
EA038792B1 (ru) 2013-05-22 2021-10-20 Элнилэм Фармасьютикалз, Инк. КОМПОЗИЦИИ НА ОСНОВЕ RNAi Serpina1 И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
US9458457B2 (en) 2013-07-03 2016-10-04 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of alpha-1 antitrypsin by double-stranded RNA
MX2017002144A (es) 2014-08-20 2017-08-15 Alnylam Pharmaceuticals Inc Agentes de ácido ribonucleico (arn) de cadena doble modificados.
TWI788312B (zh) 2016-11-23 2023-01-01 美商阿尼拉製藥公司 絲胺酸蛋白酶抑制因子Ａ１ ｉＲＮＡ組成物及其使用方法
KR20240096846A (ko) 2017-01-10 2024-06-26 애로우헤드 파마슈티컬스 인코포레이티드 알파-1 항트립신 (AAT) RNAi 작용제, AAT RNAi 작용제를 포함하는 조성물, 및 사용 방법
US10799808B2 (en) 2018-09-13 2020-10-13 Nina Davis Interactive storytelling kit

Also Published As

Publication number Publication date
AU2014268509B2 (en) 2020-10-01
CY1122159T1 (el) 2020-07-31
US9574192B2 (en) 2017-02-21
MY176712A (en) 2020-08-19
BR112015029139B1 (pt) 2022-07-12
KR20160011660A (ko) 2016-02-01
AU2020286218A1 (en) 2021-01-07
EP2999785A1 (en) 2016-03-30
JP2019107029A (ja) 2019-07-04
TW201508005A (zh) 2015-03-01
ES2676146T3 (es) 2018-07-17
PE20160030A1 (es) 2016-02-14
KR102295648B1 (ko) 2021-08-31
HRP20181030T1 (hr) 2018-08-24
CA2912826A1 (en) 2014-11-27
LT2999785T (lt) 2018-07-25
US20170114342A1 (en) 2017-04-27
JP6495250B2 (ja) 2019-04-03
KR20210110397A (ko) 2021-09-07
PT2999785T (pt) 2018-07-09
EA201592223A1 (ru) 2016-04-29
HK1221979A1 (zh) 2017-06-16
CN113018307A (zh) 2021-06-25
SG10201804472YA (en) 2018-07-30
EP2999785B1 (en) 2018-04-04
JP6931015B2 (ja) 2021-09-01
CN105408481B (zh) 2021-03-30
JP2016520312A (ja) 2016-07-14
NZ714530A (en) 2021-10-29
TWI664187B (zh) 2019-07-01
SI2999785T1 (en) 2018-08-31
US12071619B2 (en) 2024-08-27
BR112015029139A2 (ko) 2017-09-19
AU2014268509A1 (en) 2015-12-24
EP3412774A1 (en) 2018-12-12
KR102463973B1 (ko) 2022-11-07
TW201936624A (zh) 2019-09-16
IL270666B (en) 2021-07-29
KR20220154244A (ko) 2022-11-21
DK2999785T3 (en) 2018-07-23
DOP2015000288A (es) 2017-01-31
IL242637B (en) 2019-12-31
WO2014190137A1 (en) 2014-11-27
ZA201509252B (en) 2018-12-19
IL284757A (en) 2021-08-31
JP2021191278A (ja) 2021-12-16
PE20210921A1 (es) 2021-05-19
US10030244B2 (en) 2018-07-24
US20210317452A1 (en) 2021-10-14
UY35582A (es) 2014-10-31
NZ753769A (en) 2021-10-29
US10920223B2 (en) 2021-02-16
US10683504B2 (en) 2020-06-16
US20200080085A1 (en) 2020-03-12
CN105408481A (zh) 2016-03-16
RS57418B1 (sr) 2018-09-28
SG10201913872XA (en) 2020-03-30
RU2015154721A (ru) 2017-06-27
CL2015003441A1 (es) 2016-08-19
EA038792B1 (ru) 2021-10-20
PL2999785T3 (pl) 2018-09-28
US20140350071A1 (en) 2014-11-27
MX2021000656A (es) 2021-03-25
GT201500330A (es) 2019-07-19
HUE038146T2 (hu) 2018-09-28
US20180346910A1 (en) 2018-12-06

Similar Documents

Publication Publication Date Title
IL284757A (en) Preparations of SERPINA1 iRNA and methods of using them
IL285780A (en) Preparations of tmprss6 irna and methods of using them
IL282401A (en) Complementary component iRNA compositions and methods of using them
IL288931A (en) Preparations that include a part complementary to c5 irna and methods of using them
ZA202103080B (en) Serpina1 irna compositions and methods of use thereof
IL265876A (en) Preparations that include 15-ohepa and methods of using them
EP2964235A4 (en) ANTIMICROBIAL-ANTIBIOFILM COMPOSITIONS AND METHODS OF USE
IL244537A0 (en) New administration preparations and methods of their use
GB201300628D0 (en) Compositions comprising 15-OHEPA and methods of using the same