JP6694811B2 - ＲＮＡ干渉に使用するためのＲＮＡｉ剤用の３’末端キャップ - Google Patents

ＲＮＡ干渉に使用するためのＲＮＡｉ剤用の３’末端キャップ Download PDF

Info

Publication number
JP6694811B2
JP6694811B2 JP2016519876A JP2016519876A JP6694811B2 JP 6694811 B2 JP6694811 B2 JP 6694811B2 JP 2016519876 A JP2016519876 A JP 2016519876A JP 2016519876 A JP2016519876 A JP 2016519876A JP 6694811 B2 JP6694811 B2 JP 6694811B2
Authority
JP
Japan
Prior art keywords
strand
rnai agent
end cap
phosphate
spacer
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
JP2016519876A
Other languages
English (en)
Japanese (ja)
Other versions
JP2017500277A (ja
JP2017500277A5 (https=
Inventor
リー バリザ，ジェレミー
リー バリザ，ジェレミー
ブロマーズ，マルセル
フェルナンデス，セザール
ゲノ，エリン
ゴセルト，アルバール
グリニッジ，ポレット
ヒュースケン，ディーター
フンツィカー，ユルク
ジャン−シャルル ナット，フランソワ
ジャン−シャルル ナット，フランソワ
パトナイク，アヌップ
パターソン，アンドリュー
レーヌ ロンド，ジャン−ミシェル
レーヌ ロンド，ジャン−ミシェル
バイラー，ヤン
チュー，メイチョン
Original Assignee
ノバルティス アーゲー
ノバルティス アーゲー
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 ノバルティス アーゲー, ノバルティス アーゲー filed Critical ノバルティス アーゲー
Publication of JP2017500277A publication Critical patent/JP2017500277A/ja
Publication of JP2017500277A5 publication Critical patent/JP2017500277A5/ja
Application granted granted Critical
Publication of JP6694811B2 publication Critical patent/JP6694811B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
    • C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C233/11—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/17—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/22—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/34—Esters of acyclic saturated polycarboxylic acids having an esterified carboxyl group bound to an acyclic carbon atom
    • C07C69/40—Succinic acid esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D215/14—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/20—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
    • C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
    • C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
    • C07D217/16—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
    • C07D217/18—Aralkyl radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/78—Ring systems having three or more relevant rings
    • C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • 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
    • C12N2310/30—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
    • C12N2310/35—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
    • C12N2320/50—Methods for regulating/modulating their activity
    • C12N2320/51—Methods for regulating/modulating their activity modulating the chemical stability, e.g. nuclease-resistance

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyrane Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Quinoline Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines Containing Plant Substances (AREA)
JP2016519876A 2013-10-04 2014-10-01 ＲＮＡ干渉に使用するためのＲＮＡｉ剤用の３’末端キャップ Active JP6694811B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361886739P 2013-10-04 2013-10-04
US61/886,739 2013-10-04
PCT/US2014/058705 WO2015051045A2 (en) 2013-10-04 2014-10-01 3'END CAPS FOR RNAi AGENTS FOR USE IN RNA INTERFERENCE

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2019053123A Division JP6841859B2 (ja) 2013-10-04 2019-03-20 ＲＮＡ干渉に使用するためのＲＮＡｉ剤用の３’末端キャップ

Publications (3)

Publication Number Publication Date
JP2017500277A JP2017500277A (ja) 2017-01-05
JP2017500277A5 JP2017500277A5 (https=) 2017-11-09
JP6694811B2 true JP6694811B2 (ja) 2020-05-20

Family

ID=51894183

Family Applications (2)

Application Number Title Priority Date Filing Date
JP2016519876A Active JP6694811B2 (ja) 2013-10-04 2014-10-01 ＲＮＡ干渉に使用するためのＲＮＡｉ剤用の３’末端キャップ
JP2019053123A Active JP6841859B2 (ja) 2013-10-04 2019-03-20 ＲＮＡ干渉に使用するためのＲＮＡｉ剤用の３’末端キャップ

Family Applications After (1)

Application Number Title Priority Date Filing Date
JP2019053123A Active JP6841859B2 (ja) 2013-10-04 2019-03-20 ＲＮＡ干渉に使用するためのＲＮＡｉ剤用の３’末端キャップ

Country Status (8)

Country Link
US (2) US10227588B2 (https=)
EP (2) EP3052464B1 (https=)
JP (2) JP6694811B2 (https=)
KR (1) KR102298475B1 (https=)
CN (1) CN105683163B (https=)
AU (2) AU2014329560B2 (https=)
CA (2) CA3188691A1 (https=)
WO (1) WO2015051045A2 (https=)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3052627B1 (en) 2013-10-04 2018-08-22 Novartis AG Novel formats for organic compounds for use in rna interference
JP6694811B2 (ja) 2013-10-04 2020-05-20 ノバルティス アーゲー ＲＮＡ干渉に使用するためのＲＮＡｉ剤用の３’末端キャップ
EP3052107B1 (en) 2013-10-04 2018-05-02 Novartis AG Organic compounds to treat hepatitis b virus
SG10202106529XA (en) * 2015-07-21 2021-07-29 Immunogen Inc Methods of preparing cytotoxic benzodiazepine derivatives
US10577396B2 (en) * 2015-09-17 2020-03-03 Osaka University Tolan compound
EP3564375A4 (en) * 2016-12-27 2020-12-16 The University Of Tokyo ARNM FUNCTIONALIZATION PROCESS

Family Cites Families (110)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
DD123757A5 (https=) * 1974-10-22 1977-01-12
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
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
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
AU598946B2 (en) 1987-06-24 1990-07-05 Howard Florey Institute Of Experimental Physiology And Medicine Nucleoside derivatives
US4924624A (en) 1987-10-22 1990-05-15 Temple University-Of The Commonwealth System Of Higher Education 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
ATE269870T1 (de) 1989-10-24 2004-07-15 Isis Pharmaceuticals Inc 2'-modifizierte oligonukleotide
ATE157012T1 (de) 1989-11-03 1997-09-15 Univ Vanderbilt Verfahren zur in vivo-verabreichung von funktionsfähigen fremden genen
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5506351A (en) 1992-07-23 1996-04-09 Isis Pharmaceuticals Process for the preparation of 2'-O-alkyl guanosine and related compounds
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
WO1993007883A1 (en) 1991-10-24 1993-04-29 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
US5212295A (en) 1990-01-11 1993-05-18 Isis Pharmaceuticals Monomers for preparation of oligonucleotides having chiral phosphorus linkages
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
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
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US6262241B1 (en) 1990-08-13 2001-07-17 Isis Pharmaceuticals, Inc. Compound for detecting and modulating RNA activity and gene expression
US5214134A (en) 1990-09-12 1993-05-25 Sterling Winthrop Inc. Process of linking nucleosides with a siloxane bridge
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5594121A (en) 1991-11-07 1997-01-14 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified purines
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
US5466789A (en) 1992-01-21 1995-11-14 Du Pont (Uk) Limited Polyunsaturated diazonium compounds
US20030206887A1 (en) 1992-05-14 2003-11-06 David Morrissey RNA interference mediated inhibition of hepatitis B virus (HBV) using short interfering nucleic acid (siNA)
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
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
CA2159629A1 (en) 1993-03-31 1994-10-13 Sanofi Oligonucleotides with amide linkages replacing phosphodiester linkages
US5428037A (en) 1993-04-09 1995-06-27 Syntex Pharmaceuticals, Ltd. Heterocyclic derivatives in the treatment of Ischaemia and related diseases
KR970004292B1 (ko) 1993-06-17 1997-03-26 엘지전자 주식회사 브이씨알(vcr)의 수명체크장치
US5571902A (en) 1993-07-29 1996-11-05 Isis Pharmaceuticals, Inc. Synthesis of oligonucleotides
US5519134A (en) 1994-01-11 1996-05-21 Isis Pharmaceuticals, Inc. Pyrrolidine-containing monomers and oligomers
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5554746A (en) 1994-05-16 1996-09-10 Isis Pharmaceuticals, Inc. Lactam nucleic acids
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
US6166197A (en) 1995-03-06 2000-12-26 Isis Pharmaceuticals, Inc. Oligomeric compounds having pyrimidine nucleotide (S) with 2'and 5 substitutions
US5998203A (en) 1996-04-16 1999-12-07 Ribozyme Pharmaceuticals, Inc. Enzymatic nucleic acids containing 5'-and/or 3'-cap structures
US6172209B1 (en) 1997-02-14 2001-01-09 Isis Pharmaceuticals Inc. Aminooxy-modified oligonucleotides and methods for making same
US6127533A (en) 1997-02-14 2000-10-03 Isis Pharmaceuticals, Inc. 2'-O-aminooxy-modified oligonucleotides
JP3868096B2 (ja) 1997-02-27 2007-01-17 武田薬品工業株式会社 アミン誘導体、その製造法および剤
HU225960B1 (en) * 1997-02-27 2008-01-28 Takeda Pharmaceutical Amine compounds, their production and use
US6506559B1 (en) 1997-12-23 2003-01-14 Carnegie Institute Of Washington Genetic inhibition by double-stranded RNA
US6271358B1 (en) 1998-07-27 2001-08-07 Isis Pharmaceuticals, Inc. RNA targeted 2′-modified oligonucleotides that are conformationally preorganized
MXPA01003642A (es) 1998-10-09 2003-07-21 Ingene Inc Sintesis enzimatica de adnss.
US5977341A (en) 1998-11-20 1999-11-02 Isis Pharmaceuticals Inc. Antisense modulation of inhibitor-kappa B kinase-beta expression
DE19956568A1 (de) 1999-01-30 2000-08-17 Roland Kreutzer Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens
CA2386270A1 (en) 1999-10-15 2001-04-26 University Of Massachusetts Rna interference pathway genes as tools for targeted genetic interference
WO2002081628A2 (en) 2001-04-05 2002-10-17 Ribozyme Pharmaceuticals, Incorporated Modulation of gene expression associated with inflammation proliferation and neurite outgrowth, using nucleic acid based technologies
WO2003070918A2 (en) 2002-02-20 2003-08-28 Ribozyme Pharmaceuticals, Incorporated Rna interference by modified short interfering nucleic acid
US20050032733A1 (en) 2001-05-18 2005-02-10 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (SiNA)
DE10015866A1 (de) 2000-03-30 2001-10-11 Bayer Ag Aryl- und Heteroarylsulfonate
US20040259247A1 (en) 2000-12-01 2004-12-23 Thomas Tuschl Rna interference mediating small rna molecules
US6745920B2 (en) 2001-07-23 2004-06-08 Pradeep Yohanne Gupta Piston for dispensing device, dispensing device, product containing dispensing device, method of filling, and method of dispensing
US20030198627A1 (en) 2001-09-01 2003-10-23 Gert-Jan Arts siRNA knockout assay method and constructs
US6635428B2 (en) 2001-12-04 2003-10-21 Quest Diagnostics Investments Incorporated Oligonucleotides and methods for detecting hepatitis B viral nucleic acids
CN1845993B (zh) 2003-08-28 2010-06-23 诺瓦提斯公司 具有平端和3＇修饰的干扰rna双链体
CA2549720C (en) 2003-12-19 2013-10-15 Chiron Corporation Cell transfecting formulations of small interfering rna, related compositions and methods of making and use
AU2005203822A1 (en) 2004-01-12 2005-07-21 Lorus Therapeutics Inc. Antisense oligonucleotides directed to ribonucleotide reductase R2 and uses thereof in combination therapies for the treatment of cancer
EP1752536A4 (en) 2004-05-11 2008-04-16 Alphagen Co Ltd POLYNUCLEOTIDE CAUSING RNA INTERFERENCE AND METHOD OF REGULATING GENE EXPRESSION WITH THE USE OF THE SAME
CA2577036A1 (en) 2004-08-18 2006-02-23 Genesense Technologies Inc. Small interfering rna molecules against ribonucleotide reductase and uses thereof
US20060142228A1 (en) 2004-12-23 2006-06-29 Ambion, Inc. Methods and compositions concerning siRNA's as mediators of RNA interference
WO2007107162A2 (en) 2006-03-23 2007-09-27 Santaris Pharma A/S Small internally segmented interfering rna
GB0608838D0 (en) 2006-05-04 2006-06-14 Novartis Ag Organic compounds
FR2909555B1 (fr) 2006-12-11 2009-01-30 Oreal Emulsion e/h a effet correcteur pour la peau
CN101663275B (zh) * 2007-04-24 2013-01-02 默克专利股份有限公司 用于液晶混合物的吡啶化合物
BRPI0811170B8 (pt) 2007-05-22 2021-05-25 Arcturus Therapeutics Inc oligonucleotídeos de rna e complexos de rna substituídos por hidroximetila
US8188060B2 (en) 2008-02-11 2012-05-29 Dharmacon, Inc. Duplex oligonucleotides with enhanced functionality in gene regulation
DE102008037790A1 (de) 2008-08-14 2010-02-18 Merck Patent Gmbh Bicyclische Triazolderivate
WO2010032147A2 (en) 2008-09-19 2010-03-25 Pfizer Inc. Hydroxamic acid derivatives useful as antibacterial agents
WO2010055789A1 (ja) 2008-11-14 2010-05-20 独立行政法人科学技術振興機構 オリゴヌクレオチド誘導体、ラベル化剤及びその利用
US8772308B2 (en) 2009-01-16 2014-07-08 Virginia Commonwealth University Non-peptidyl, potent, and selective mu opioid receptor antagonists
AU2010206374B2 (en) 2009-01-23 2013-01-17 Gloriana Therapeutics Sarl Improved cell lines and their use in encapsulated cell biodelivery
US8207138B2 (en) 2009-05-19 2012-06-26 Medtronic, Inc. Methods and devices for improved efficiency of RNA delivery to cells
SG177560A1 (en) 2009-07-06 2012-03-29 Hoffmann La Roche Bi-specific digoxigenin binding antibodies
AR078173A1 (es) 2009-09-15 2011-10-19 Sanofi Aventis Bifeniloximetil dihidro oxazolopirimidinonas sustituidas, su preparacion y su uso
KR101718534B1 (ko) * 2009-12-09 2017-03-22 닛토덴코 가부시키가이샤 Ｈｓｐ４７ 발현의 조절
US8877439B2 (en) * 2009-12-17 2014-11-04 Sirna Therapeutics, Inc. Method for rapidly evaluating performance of short interfering RNA with novel chemical modifications
WO2011076807A2 (en) 2009-12-23 2011-06-30 Novartis Ag Lipids, lipid compositions, and methods of using them
WO2012027206A1 (en) 2010-08-24 2012-03-01 Merck Sharp & Dohme Corp. SINGLE-STRANDED RNAi AGENTS CONTAINING AN INTERNAL, NON-NUCLEIC ACID SPACER
JP2014122161A (ja) * 2011-03-31 2014-07-03 Astellas Pharma Inc ピラゾール化合物
HRP20181564T1 (hr) 2011-06-30 2018-11-30 Arrowhead Pharmaceuticals, Inc. Pripravci i postupci za inhibiciju ekspresije gena virusa hepatitisa b
HK1202543A1 (en) * 2012-01-28 2015-10-02 Merck Patent Gmbh Azaheterocyclic compounds
US9504747B2 (en) 2013-03-08 2016-11-29 Novartis Ag Lipids and lipid compositions for the delivery of active agents
EP3608308B1 (en) 2013-03-08 2021-07-21 Novartis AG Lipids and lipid compositions for the delivery of active agents
WO2015005499A1 (ja) * 2013-07-12 2015-01-15 住友化学株式会社 テトラゾリノン化合物及びその用途
WO2015051044A2 (en) 2013-10-04 2015-04-09 Novartis Ag Novel formats for organic compounds for use in rna interference
EP3052627B1 (en) 2013-10-04 2018-08-22 Novartis AG Novel formats for organic compounds for use in rna interference
EP3052107B1 (en) 2013-10-04 2018-05-02 Novartis AG Organic compounds to treat hepatitis b virus
JP6694811B2 (ja) 2013-10-04 2020-05-20 ノバルティス アーゲー ＲＮＡ干渉に使用するためのＲＮＡｉ剤用の３’末端キャップ
WO2015051135A2 (en) 2013-10-04 2015-04-09 Novartis Ag Organic compositions to treat hepcidin-related diseases
EP4019506A1 (en) 2013-12-19 2022-06-29 Novartis AG Lipids and lipid compositions for the delivery of active agents
ES2895651T3 (es) 2013-12-19 2022-02-22 Novartis Ag Lípidos y composiciones lipídicas para la administración de agentes activos
EP3169309B1 (en) 2014-07-16 2023-05-10 Novartis AG Method of encapsulating a nucleic acid in a lipid nanoparticle host
US10125092B2 (en) 2014-09-05 2018-11-13 Novartis Ag Lipids and lipid compositions for the delivery of active agents

Also Published As

Publication number Publication date
AU2014329560B2 (en) 2017-03-02
EP3722277A2 (en) 2020-10-14
JP2019135236A (ja) 2019-08-15
US20160304863A1 (en) 2016-10-20
CN105683163B (zh) 2018-11-09
EP3052464A2 (en) 2016-08-10
US11008570B2 (en) 2021-05-18
CN105683163A (zh) 2016-06-15
US10227588B2 (en) 2019-03-12
EP3052464B1 (en) 2020-04-15
AU2014329560A1 (en) 2016-04-07
JP2017500277A (ja) 2017-01-05
EP3722277A3 (en) 2021-01-20
WO2015051045A3 (en) 2015-07-30
WO2015051045A2 (en) 2015-04-09
CA2925129C (en) 2023-04-04
AU2017203685B2 (en) 2019-08-08
US20190390196A1 (en) 2019-12-26
CA2925129A1 (en) 2015-04-09
KR102298475B1 (ko) 2021-09-06
AU2017203685A1 (en) 2017-06-15
CA3188691A1 (en) 2015-04-09
KR20160067901A (ko) 2016-06-14
JP6841859B2 (ja) 2021-03-10

Similar Documents

Publication Publication Date Title
EP3052627B1 (en) Novel formats for organic compounds for use in rna interference
JP7625544B2 (ja) キラル制御
JP6841859B2 (ja) ＲＮＡ干渉に使用するためのＲＮＡｉ剤用の３’末端キャップ
JP6546161B2 (ja) Ｂ型肝炎ウイルスを治療するための有機化合物
JP6757373B2 (ja) キラルデザイン
WO2015051044A2 (en) Novel formats for organic compounds for use in rna interference
WO2025063238A1 (ja) ホスホランバンの発現を抑制するｓｉＲＮＡ

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20170929

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20170929

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20180621

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20180710

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20181009

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20181225

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20190320

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20190611

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20190911

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20191224

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20200319

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20200407

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20200420

R150 Certificate of patent or registration of utility model

Ref document number: 6694811

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250