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
JP2017500277A5 (enExample
JP2017500277A (ja
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)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pyridine Compounds (AREA)
  • Pyrane Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Quinoline Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Medicinal Preparation (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 (enExample) 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 (enExample)
EP (2) EP3722277A3 (enExample)
JP (2) JP6694811B2 (enExample)
KR (1) KR102298475B1 (enExample)
CN (1) CN105683163B (enExample)
AU (2) AU2014329560B2 (enExample)
CA (2) CA3188691A1 (enExample)
WO (1) WO2015051045A2 (enExample)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015051366A2 (en) 2013-10-04 2015-04-09 Novartis Ag Novel formats for organic compounds for use in rna interference
EP3722277A3 (en) 2013-10-04 2021-01-20 Novartis AG 3'end caps for rna-interferring agents for use in rna
WO2015050871A2 (en) 2013-10-04 2015-04-09 Novartis Ag Organic compounds to treat hepatitis b virus
EP3778602B1 (en) * 2015-07-21 2023-07-12 ImmunoGen, Inc. Methods of preparing cytotoxic benzodiazepine derivatives
WO2017047807A1 (ja) * 2015-09-17 2017-03-23 国立大学法人大阪大学 トラン化合物
CN110168090B (zh) 2016-12-27 2023-07-18 国立大学法人东京大学 mRNA的功能化方法
WO2026130744A1 (en) * 2024-12-19 2026-06-25 Silence Therapeutics Gmbh Nucleic acids comprising locked nucleic acids (lna) for inhibiting gene expression in a cell

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 (enExample) 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
EP0366685B1 (en) 1987-06-24 1994-10-19 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
WO1991006556A1 (en) 1989-10-24 1991-05-16 Gilead Sciences, Inc. 2' modified oligonucleotides
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
EP0452457B1 (en) 1989-11-03 1997-08-20 Vanderbilt University Method of in vivo delivery of functioning foreign genes
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
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
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
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
US5506351A (en) 1992-07-23 1996-04-09 Isis Pharmaceuticals Process for the preparation of 2'-O-alkyl guanosine and related compounds
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
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
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
JP2823959B2 (ja) 1991-10-24 1998-11-11 アイシス・ファーマシューティカルス・インコーポレーテッド 改良された取り込みおよびその他の性質を持つ誘導化オリゴヌクレオチド
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
HU9501974D0 (en) 1993-03-31 1995-09-28 Sterling Winthrop Inc 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
WO1998038156A1 (en) * 1997-02-27 1998-09-03 Takeda Chemical Industries, Ltd. Amine compounds, their production and use as amyloid-beta production inhibitors
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
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
BR9914772A (pt) 1998-10-09 2001-12-11 Ingene Inc Conjunto de elementos genéticos, vetor, célulahospedeira, conjunto para a produção de umasequência de ácido nucléico, método para aprodução in vivo ou in vitro de uma sequência deácido nucléico, transcrição de cdna, molécula deácido nucléico inibidor, transcrição de mrna,molécula heteroduplex e composiçãofarmacêutica
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
EP1235842A4 (en) 1999-10-15 2003-04-23 Univ Massachusetts Rna interference pathway genes as tools for targeted genetic interference
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)
WO2003070918A2 (en) 2002-02-20 2003-08-28 Ribozyme Pharmaceuticals, Incorporated Rna interference by modified short interfering nucleic acid
DE10015866A1 (de) * 2000-03-30 2001-10-11 Bayer Ag Aryl- und Heteroarylsulfonate
CN100523215C (zh) 2000-12-01 2009-08-05 马普科技促进协会 介导rna干涉的小rna分子
EP1386004A4 (en) 2001-04-05 2005-02-16 Ribozyme Pharm Inc MODULATION OF GENE EXPRESSION ASSOCIATED WITH INFLAMMATORY PROLIFERATION AND GROWTH OF NEURITIES BY METHODS INVOLVING NUCLEIC ACID
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
AU2004305111B2 (en) 2003-12-19 2011-04-28 Novartis Vaccines And Diagnostics, Inc. Cell transfecting formulations of small interfering RNA, related compositions and methods of making and use
EP1715896A4 (en) 2004-01-12 2009-01-07 Lorus Therapeutics Inc ANTISENSE OLIGONUCLEOTIDES DIRECTED AGAINST RIBONUCLEOTIDE REDUCTASE R2 AND USE THEREOF IN POLYTHERAPIES FOR THE TREATMENT OF CANCER
CA2566286A1 (en) 2004-05-11 2005-12-08 Rnai Co., Ltd. Polynucleotide causing rna interfere and method of regulating gene expression with the use of the same
WO2006017932A1 (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
ES2556128T3 (es) 2006-03-23 2016-01-13 Roche Innovation Center Copenhagen A/S ARN interfiriente pequeño internamente segmentado
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
EP2137154B1 (de) * 2007-04-24 2015-07-15 Merck Patent GmbH Pyridin-verbindungen für flüssigkristalline mischungen
NZ580712A (en) 2007-05-22 2011-12-22 Marina Biotech Inc Hydroxymethyl substituted rna oligonucleotides and rna complexes containing acyclic monomers
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
US8722686B2 (en) * 2008-09-19 2014-05-13 Pfizer Inc. Hydroxamic acid derivatives useful as antibacterial agents
US8354515B2 (en) 2008-11-14 2013-01-15 Japan Science And Technology Agency Oligonucleotide derivative, labeling agent and use for labeling agent
EP2387577A4 (en) 2009-01-16 2012-10-17 Univ Virginia Commonwealth NON-PEPTIDE, POWERFUL AND SELECTIVE ANTAGONISTS OF MU OPIOID RECEPTORS
CA2750027C (en) 2009-01-23 2020-11-10 Nsgene A/S 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
US9050375B2 (en) 2009-07-06 2015-06-09 Hoffmann-La Roche, Inc. Bi-specific digoxigenin binding antibodies
AR078173A1 (es) * 2009-09-15 2011-10-19 Sanofi Aventis Bifeniloximetil dihidro oxazolopirimidinonas sustituidas, su preparacion y su uso
CA2781896C (en) * 2009-12-09 2021-03-30 Nitto Denko Corporation Modulation of hsp47 expression
EP2513337A4 (en) * 2009-12-17 2013-12-25 Merck Sharp & Dohme METHOD FOR QUICKLY EVALUATING THE PERFORMANCE OF SHORT INTERFERING RNA WITH NEW CHEMICAL MODIFICATIONS
WO2011076807A2 (en) 2009-12-23 2011-06-30 Novartis Ag Lipids, lipid compositions, and methods of using them
JP6106085B2 (ja) 2010-08-24 2017-03-29 サーナ・セラピューティクス・インコーポレイテッドＳｉｒｎａ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． 内部非核酸スペーサーを含む一本鎖ＲＮＡｉ剤
JP2014122161A (ja) * 2011-03-31 2014-07-03 Astellas Pharma Inc ピラゾール化合物
PT2726613T (pt) 2011-06-30 2018-10-26 Arrowhead Pharmaceuticals Inc Composições e métodos para inibição da expressão de genes do vírus da hepatite b
CN104080773B (zh) * 2012-01-28 2016-12-28 默克专利股份公司 氮杂环化合物
ES2887254T3 (es) 2013-03-08 2021-12-22 Novartis Ag Lípidos y composiciones lipídicas para el suministro de agentes activos
US9504747B2 (en) 2013-03-08 2016-11-29 Novartis Ag Lipids and lipid compositions for the delivery of active agents
US9888688B2 (en) 2013-07-12 2018-02-13 Sumitomo Chemical Company, Limited Tetrazolinone compounds and applications thereof
EP3722277A3 (en) 2013-10-04 2021-01-20 Novartis AG 3'end caps for rna-interferring agents for use in rna
WO2015050871A2 (en) * 2013-10-04 2015-04-09 Novartis Ag Organic compounds to treat hepatitis b virus
WO2015051366A2 (en) 2013-10-04 2015-04-09 Novartis Ag Novel formats for organic compounds for use in rna interference
WO2015051135A2 (en) 2013-10-04 2015-04-09 Novartis Ag Organic compositions to treat hepcidin-related diseases
WO2015051044A2 (en) 2013-10-04 2015-04-09 Novartis Ag Novel formats for organic compounds for use in rna interference
US10426737B2 (en) 2013-12-19 2019-10-01 Novartis Ag Lipids and lipid compositions for the delivery of active agents
US10059655B2 (en) 2013-12-19 2018-08-28 Novartis Ag Lipids and lipid compositions for the delivery of active agents
CN106794141B (zh) 2014-07-16 2021-05-28 诺华股份有限公司 将核酸包封在脂质纳米粒主体中的方法
ES2969956T3 (es) 2014-09-05 2024-05-23 Novartis Ag Lípidos y composiciones lipídicas para el suministro de agentes activos

Also Published As

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

Similar Documents

Publication Publication Date Title
EP3052627B1 (en) Novel formats for organic compounds for use in rna interference
JP6841859B2 (ja) ＲＮＡ干渉に使用するためのＲＮＡｉ剤用の３’末端キャップ
JP7625544B2 (ja) キラル制御
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
AU2019252680A1 (en) Oligonucleotide compositions and methods of use thereof
WO2025063238A1 (ja) ホスホランバンの発現を抑制するｓｉＲＮＡ
WO2015051044A2 (en) Novel formats for organic compounds for use in rna interference

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