JP7803850B2 - 結合修飾オリゴマー化合物及びその使用 - Google Patents

結合修飾オリゴマー化合物及びその使用

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Publication number
JP7803850B2
JP7803850B2 JP2022509588A JP2022509588A JP7803850B2 JP 7803850 B2 JP7803850 B2 JP 7803850B2 JP 2022509588 A JP2022509588 A JP 2022509588A JP 2022509588 A JP2022509588 A JP 2022509588A JP 7803850 B2 JP7803850 B2 JP 7803850B2
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Prior art keywords
modified oligonucleotide
substituted
nucleoside
oligomeric compound
alkyl
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JP2022509588A
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English (en)
Japanese (ja)
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JP2022544587A (ja
JP2022544587A5 (enExample
Inventor
リャン，シュエ－ハイ
セス，プニット・ピー
アンダーソン，ブルック・エイ
ドルリー，ザ・サード，ウィリアム・ジョン
ウースターガード，マイケル
ミガワ，マイケル・ティー
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Ionis Pharmaceuticals Inc
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Ionis Pharmaceuticals Inc
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Publication of JP2022544587A publication Critical patent/JP2022544587A/ja
Publication of JP2022544587A5 publication Critical patent/JP2022544587A5/ja
Priority to JP2025171677A priority Critical patent/JP2026012736A/ja
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • 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
    • A61K31/01—Hydrocarbons
    • A61K31/015—Hydrocarbons carbocyclic
    • 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
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
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    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
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    • 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
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/11—Antisense
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    • 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]
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/314—Phosphoramidates
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/314—Phosphoramidates
    • C12N2310/3145—Phosphoramidates with the nitrogen in 3' or 5'-position
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    • 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
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/341—Gapmers, i.e. of the type ===---===
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol
    • C—CHEMISTRY; METALLURGY
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    • 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
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    • 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
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    • C12N2320/50—Methods for regulating/modulating their activity
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    • C12N2330/00—Production
    • C12N2330/30—Production chemically synthesised

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  • Zoology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
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  • Medicinal Chemistry (AREA)
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  • Physics & Mathematics (AREA)
  • Epidemiology (AREA)
  • Toxicology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
JP2022509588A 2019-08-15 2020-08-14 結合修飾オリゴマー化合物及びその使用 Active JP7803850B2 (ja)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2025171677A JP2026012736A (ja) 2019-08-15 2025-10-10 結合修飾オリゴマー化合物及びその使用

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US201962887525P 2019-08-15 2019-08-15
US62/887,525 2019-08-15
US201962953121P 2019-12-23 2019-12-23
US62/953,121 2019-12-23
US202062989442P 2020-03-13 2020-03-13
US62/989,442 2020-03-13
US202063050042P 2020-07-09 2020-07-09
US63/050,042 2020-07-09
PCT/US2020/046561 WO2021030778A1 (en) 2019-08-15 2020-08-14 Linkage modified oligomeric compounds and uses thereof

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JP2022544587A JP2022544587A (ja) 2022-10-19
JP2022544587A5 JP2022544587A5 (enExample) 2023-08-16
JP7803850B2 true JP7803850B2 (ja) 2026-01-21

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JP2025171677A Pending JP2026012736A (ja) 2019-08-15 2025-10-10 結合修飾オリゴマー化合物及びその使用

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Country Status (6)

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US (3) US11629348B2 (enExample)
EP (1) EP4013767A4 (enExample)
JP (2) JP7803850B2 (enExample)
KR (1) KR20220062517A (enExample)
CN (2) CN121779475A (enExample)
WO (1) WO2021030778A1 (enExample)

Families Citing this family (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20220062517A (ko) 2019-08-15 2022-05-17 아이오니스 파마수티컬즈, 인코포레이티드 결합 변형된 올리고머 화합물 및 이의 용도
US12491255B2 (en) 2019-10-14 2025-12-09 Aro Biotherapeutics Company EPCAM binding fibronectin type III domains
WO2021076546A1 (en) 2019-10-14 2021-04-22 Aro Biotherapeutics Company Cd71 binding fibronectin type iii domains
CN111041025B (zh) 2019-12-17 2021-06-18 深圳市瑞吉生物科技有限公司 基于结合N-乙酰半乳糖胺多肽的mRNA靶向分子及其制备方法
PH12022552258A1 (en) 2020-02-28 2023-11-20 Ionis Pharmaceuticals Inc Compounds and methods for modulating smn2
CN111744019B (zh) 2020-07-01 2023-08-04 深圳瑞吉生物科技有限公司 基于甘露糖的mRNA靶向递送系统及其应用
GB2603454A (en) 2020-12-09 2022-08-10 Ucl Business Ltd Novel therapeutics for the treatment of neurodegenerative disorders
WO2022174053A1 (en) * 2021-02-11 2022-08-18 Ionis Pharmaceuticals, Inc. Linkage modified oligomeric compounds and uses thereof
IL307582A (en) 2021-04-14 2023-12-01 Aro Biotherapeutics Company CD71-binding domains of the fibronectin type
US12239710B2 (en) 2021-04-14 2025-03-04 Aro Biotherapeutics Company FN3 domain-siRNA conjugates and uses thereof
IL309503A (en) * 2021-06-24 2024-02-01 Lilly Co Eli Innovative therapeutic delivery parts and their uses
CA3224145A1 (en) * 2021-06-24 2022-12-29 Melissa Ann Bellinger Novel rna therapeutics and uses thereof
CN117480254A (zh) * 2021-06-30 2024-01-30 Ionis制药公司 合成键修饰的寡聚化合物的方法
US20240360448A1 (en) * 2021-08-18 2024-10-31 Ionis Pharmaceuticals, Inc. Linkage modified oligomeric compounds and uses thereof
US20240360449A1 (en) * 2021-08-27 2024-10-31 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating scn1a expression
WO2023076710A1 (en) * 2021-11-01 2023-05-04 A2Tbio Llc Stabilized rna agents
GB202117758D0 (en) 2021-12-09 2022-01-26 Ucl Business Ltd Therapeutics for the treatment of neurodegenerative disorders
WO2023149563A1 (ja) * 2022-02-04 2023-08-10 日東電工株式会社 オリゴヌクレオチドを製造する方法
JPWO2023176863A1 (enExample) * 2022-03-16 2023-09-21
JP2025516680A (ja) 2022-05-13 2025-05-30 アルナイラム ファーマシューティカルズ， インコーポレイテッド 一本鎖ループオリゴヌクレオチド
WO2023245060A2 (en) 2022-06-15 2023-12-21 Arrowhead Pharmaceuticals, Inc. Rnai agents for inhibiting expression of superoxide dismutase 1 (sod1), compositions thereof, and methods of use
CN119365600A (zh) * 2022-06-17 2025-01-24 豪夫迈·罗氏有限公司 靶向颗粒蛋白前体的反义寡核苷酸
CN119403816A (zh) * 2022-07-22 2025-02-07 住友化学株式会社 寡核苷酸的制造方法
JP2026508347A (ja) * 2023-03-01 2026-03-10 ウェイブ ライフ サイエンシズ リミテッド Ｒｎａ干渉のための二本鎖オリゴヌクレオチド組成物およびそれに関する方法
GB202304363D0 (en) 2023-03-24 2023-05-10 Proqr Therapeutics Ii Bv Chemically modified antisense oligonucleotides for use in RNA editing
CN121002181A (zh) 2023-03-27 2025-11-21 ProQR治疗上市公司Ⅱ 用于治疗肝脏疾病的反义寡核苷酸
UY40699A (es) 2023-04-05 2024-08-30 Ionis Pharmaceuticals Inc Compuestos y métodos para reducir la expresión de pln
TW202442242A (zh) 2023-04-21 2024-11-01 德商瑟卡爾納製藥有限兩合公司 Nrp1-特異性反義寡核苷酸及其等在預防及/或治療疾病的用途
WO2024227059A2 (en) * 2023-04-27 2024-10-31 Aligos Therapeutics, Inc. Short interfering nucleic acid (sina) molecules targeting angptl 3 and angptl 8 and methods of using the same
WO2024229377A1 (en) * 2023-05-03 2024-11-07 Ionis Pharmaceuticals, Inc. Sugar modified oligonucleotides and uses thereof
CN121729491A (zh) 2023-05-12 2026-03-24 阿尔尼拉姆制药公司 单链环寡核苷酸
AR132964A1 (es) 2023-06-16 2025-08-13 Proqr Therapeutics Ii Bv Oligonucleótidos antisentido para el tratamiento de enfermedades neurodegenerativas
CN121794378A (zh) * 2023-08-15 2026-04-03 艾尔纳公司 用于rna编辑的化学修饰的反义寡核苷酸（aso）及组合物
WO2025051946A1 (en) 2023-09-07 2025-03-13 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of metabolic disorders
AU2024342933A1 (en) 2023-09-14 2026-03-26 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing apociii expression
CN116949044B (zh) * 2023-09-20 2023-12-12 北京炫景瑞医药科技有限公司 一种双链寡链核苷酸、包含该双链寡核苷酸的缀合物以及它们的用途
WO2025064821A2 (en) 2023-09-21 2025-03-27 Ionis Pharmaceuticals, Inc. Compounds and methods for inhibiting lpa
GB202314724D0 (en) 2023-09-26 2023-11-08 Astrazeneca Ab compounds and methods for reducing psd3 expression
WO2025096809A1 (en) 2023-10-31 2025-05-08 Korro Bio, Inc. Oligonucleotides comprising phosphoramidate internucleotide linkages
AU2024379264A1 (en) 2023-11-16 2026-05-14 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of classic galactosemia
TW202542312A (zh) 2023-12-27 2025-11-01 德商瑟卡爾納製藥有限兩合公司 Ｍｌｋｌ－特異性反義寡核苷酸及其等在由如細胞壞死性凋亡之細胞死亡形式所導致的病症之預防及／或治療的用途
GB202404661D0 (en) 2024-04-02 2024-05-15 Proqr Therapeutics Ii Bv Antisense oligoncleotides for the treatment of liver disease
WO2025224230A1 (en) 2024-04-25 2025-10-30 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of fatty liver disease
WO2025250953A1 (en) * 2024-05-31 2025-12-04 Ionis Pharmaceuticals, Inc. Linkage modified oligomeric agents and uses thereof
WO2026022136A1 (en) 2024-07-23 2026-01-29 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of metabolic disorders
WO2026050243A1 (en) 2024-08-26 2026-03-05 Korro Bio, Inc. Galnac conjugated oligonucleotides for rna editing
WO2026062247A1 (en) 2024-09-20 2026-03-26 Astrazeneca Ab Liquid-phase oligonucleotide synthesis using 2-(2-nitrophenyl)propyloxycarbonyl (nppoc) as a protecting group
WO2026068781A1 (en) 2024-09-30 2026-04-02 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of liver disease
WO2026087533A1 (en) 2024-10-21 2026-04-30 Secarna Pharmaceuticals Gmbh & Co. Kg Nrp1-specific antisense oligonucleotides with reduced off-target binding for use in preventing and/or treating cancer
WO2026093339A1 (en) 2024-10-29 2026-05-07 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of peroxisome biogenesis disorders in the zellweger spectrum (pbd-zsd)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009516521A (ja) 2005-11-23 2009-04-23 エフ．ホフマン−ラ ロシュ アーゲー リン酸塩模倣物を含むポリヌクレオチド
JP2010524874A (ja) 2007-04-18 2010-07-22 エフ．ホフマン−ラ ロシュ アーゲー α−リン酸擬似体を有するヌクレオチド
WO2018156056A1 (ru) 2017-02-21 2018-08-30 Дмитрий Александрович СТЕЦЕНКО Модифицированные олигонуклеотиды, активирующие рнказу н

Family Cites Families (169)

* 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
US4458066A (en) 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
US4500707A (en) 1980-02-29 1985-02-19 University Patents, Inc. Nucleosides useful in the preparation of polynucleotides
US5132418A (en) 1980-02-29 1992-07-21 University Patents, Inc. Process for preparing polynucleotides
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
US4668777A (en) 1981-03-27 1987-05-26 University Patents, Inc. Phosphoramidite nucleoside compounds
US4973679A (en) 1981-03-27 1990-11-27 University Patents, Inc. Process for oligonucleo tide synthesis using phosphormidite intermediates
US4415732A (en) 1981-03-27 1983-11-15 University Patents, Inc. Phosphoramidite compounds and processes
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
DE3329892A1 (de) 1983-08-18 1985-03-07 Köster, Hubert, Prof. Dr., 2000 Hamburg Verfahren zur herstellung von oligonucleotiden
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
USRE34036E (en) 1984-06-06 1992-08-18 National Research Development Corporation Data transmission using a transparent tone-in band system
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
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
FR2575751B1 (fr) 1985-01-08 1987-04-03 Pasteur Institut Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
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
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
DE3788914T2 (de) 1986-09-08 1994-08-25 Ajinomoto Kk Verbindungen zur Spaltung von RNS an eine spezifische Position, Oligomere, verwendet bei der Herstellung dieser Verbindungen und Ausgangsprodukte für die Synthese dieser Oligomere.
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
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
DE3851889T2 (de) 1987-06-24 1995-04-13 Florey Howard Inst Nukleosid-derivate.
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
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
EP0348458B1 (en) 1987-11-30 1997-04-09 University Of Iowa Research Foundation Dna molecules stabilized by modifications of the 3'-terminal phosphodiester linkage and their use as nucleic acid probes and as therapeutic agents to block the expression of specifically targeted genes
US5403711A (en) 1987-11-30 1995-04-04 University Of Iowa Research Foundation Nucleic acid hybridization and amplification method for detection of specific sequences in which a complementary labeled nucleic acid probe is cleaved
WO1989009221A1 (en) 1988-03-25 1989-10-05 University Of Virginia Alumni Patents Foundation Oligonucleotide n-alkylphosphoramidates
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
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
US5194599A (en) 1988-09-23 1993-03-16 Gilead Sciences, Inc. Hydrogen phosphonodithioate compositions
US5256775A (en) 1989-06-05 1993-10-26 Gilead Sciences, Inc. Exonuclease-resistant oligonucleotides
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
US5721218A (en) 1989-10-23 1998-02-24 Gilead Sciences, Inc. Oligonucleotides with inverted polarity
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
DK0942000T3 (da) 1989-10-24 2004-11-01 Isis Pharmaceuticals Inc 2'-modificerede oligonukleotider
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5130302A (en) 1989-12-20 1992-07-14 Boron Bilogicals, Inc. Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
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
US5623065A (en) 1990-08-13 1997-04-22 Isis Pharmaceuticals, Inc. Gapped 2' modified oligonucleotides
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US5220007A (en) 1990-02-15 1993-06-15 The Worcester Foundation For Experimental Biology Method of site-specific alteration of RNA and production of encoded polypeptides
US5149797A (en) 1990-02-15 1992-09-22 The Worcester Foundation For Experimental Biology Method of site-specific alteration of rna and production of encoded polypeptides
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
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
ATE167523T1 (de) 1990-05-11 1998-07-15 Microprobe Corp Teststreifen zum eintauchen für nukleinsäure- hybridisierungsassays und verfahren zur kovalenten immobilisierung von oligonucleotiden
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5378825A (en) 1990-07-27 1995-01-03 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
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
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5223618A (en) 1990-08-13 1993-06-29 Isis Pharmaceuticals, Inc. 4'-desmethyl nucleoside analog compounds
US5386023A (en) 1990-07-27 1995-01-31 Isis Pharmaceuticals Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling
JPH06502300A (ja) 1990-08-03 1994-03-17 サノフィ 遺伝子発現の抑制のための化合物及び方法
US5177196A (en) 1990-08-16 1993-01-05 Microprobe Corporation Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof
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
US5672697A (en) 1991-02-08 1997-09-30 Gilead Sciences, Inc. Nucleoside 5'-methylene phosphonates
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
ES2103918T3 (es) 1991-10-17 1997-10-01 Ciba Geigy Ag Nucleosidos biciclicos, oligonucleotidos, procedimiento para su obtencion y productos intermedios.
US5594121A (en) 1991-11-07 1997-01-14 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified purines
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
TW393513B (en) 1991-11-26 2000-06-11 Isis Pharmaceuticals Inc Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines
EP1256589A3 (en) 1991-11-26 2003-09-17 Isis Pharmaceuticals, Inc. Oligomers containing modified pyrimidines
US5792608A (en) 1991-12-12 1998-08-11 Gilead Sciences, Inc. Nuclease stable and binding competent oligomers and methods for their use
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
US5700922A (en) 1991-12-24 1997-12-23 Isis Pharmaceuticals, Inc. PNA-DNA-PNA chimeric macromolecules
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
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
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
US5652355A (en) 1992-07-23 1997-07-29 Worcester Foundation For Experimental Biology Hybrid oligonucleotide phosphorothioates
AU678769B2 (en) 1992-07-27 1997-06-12 Hybridon, Inc. Oligonucleotide alkylphosphonothioates
AU6165494A (en) 1993-01-25 1994-08-15 Hybridon, Inc. Oligonucleotide alkylphosphonates and alkylphosphonothioates
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
GB9304620D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Compounds
WO1994022864A1 (en) 1993-03-30 1994-10-13 Sterling Winthrop Inc. Acyclic nucleoside analogs and oligonucleotide sequences containing them
CA2159629A1 (en) 1993-03-31 1994-10-13 Sanofi Oligonucleotides with amide linkages replacing phosphodiester linkages
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
CN1048254C (zh) 1993-12-09 2000-01-12 托马斯杰弗逊大学 用于将预定的改变引入靶基因中的化合物
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
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
DE59510742D1 (de) 1994-04-27 2003-08-14 Novartis Ag Nukleoside und Oligonukleotide mit 2'-Ethergruppen
US5646269A (en) 1994-04-28 1997-07-08 Gilead Sciences, Inc. Method for oligonucleotide analog synthesis
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
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
US5652356A (en) 1995-08-17 1997-07-29 Hybridon, Inc. Inverted chimeric and hybrid oligonucleotides
US20080119427A1 (en) 1996-06-06 2008-05-22 Isis Pharmaceuticals, Inc. Double Strand Compositions Comprising Differentially Modified Strands for Use in Gene Modulation
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
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
CA2303299C (en) 1997-09-12 2016-02-23 Exiqon A/S Oligonucleotide analogues
US6043352A (en) 1998-08-07 2000-03-28 Isis Pharmaceuticals, Inc. 2'-O-Dimethylaminoethyloxyethyl-modified oligonucleotides
US6365577B1 (en) * 1998-10-26 2002-04-02 Avi Biopharma, Inc. p53 antisense agent and method
PT1152009E (pt) 1999-02-12 2005-03-31 Sankyo Co Novos analogos de nucleosidos e oligonucleotidos
US7084125B2 (en) 1999-03-18 2006-08-01 Exiqon A/S Xylo-LNA analogues
NZ514348A (en) 1999-05-04 2004-05-28 Exiqon As L-ribo-LNA analogues
JP4151751B2 (ja) 1999-07-22 2008-09-17 第一三共株式会社 新規ビシクロヌクレオシド類縁体
US7053199B2 (en) 2000-08-29 2006-05-30 Takeshi Imanishi Nucleoside analogs and oligonucleotide derivatives containing these analogs
US6693187B1 (en) 2000-10-17 2004-02-17 Lievre Cornu Llc Phosphinoamidite carboxlates and analogs thereof in the synthesis of oligonucleotides having reduced internucleotide charge
US6426220B1 (en) 2000-10-30 2002-07-30 Isis Pharmaceuticals, Inc. Antisense modulation of calreticulin expression
WO2003002587A2 (en) 2001-06-29 2003-01-09 Micrologix Biotech Inc. Phosphoramide containing nucleic acid-based compounds and libraries as antivirals
WO2003020739A2 (en) 2001-09-04 2003-03-13 Exiqon A/S Novel lna compositions and uses thereof
WO2004041889A2 (en) 2002-11-05 2004-05-21 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
EP1661905B9 (en) 2003-08-28 2012-12-19 IMANISHI, Takeshi Novel artificial nucleic acids of n-o bond crosslinkage type
JP5379347B2 (ja) 2003-09-18 2013-12-25 アイシス ファーマシューティカルズ， インコーポレーテッド ４’−チオヌクレオシドおよびオリゴマー化合物
ES2351674T3 (es) 2006-01-27 2011-02-09 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos modificados en la posición 6.
DK2021472T3 (da) 2006-05-05 2011-09-19 Isis Pharmaceuticals Inc Forbindelser og fremgangsmåder til modulering af genekspression
CA2651453C (en) 2006-05-11 2014-10-14 Isis Pharmaceuticals, Inc. 5'-modified bicyclic nucleic acid analogs
WO2008101157A1 (en) 2007-02-15 2008-08-21 Isis Pharmaceuticals, Inc. 5'-substituted-2'-f modified nucleosides and oligomeric compounds prepared therefrom
WO2008109080A2 (en) 2007-03-01 2008-09-12 Siemens Medical Solutions Usa, Inc. Nucleoside based proliferation imaging markers
EP2170917B1 (en) 2007-05-30 2012-06-27 Isis Pharmaceuticals, Inc. N-substituted-aminomethylene bridged bicyclic nucleic acid analogs
EP2173760B2 (en) 2007-06-08 2015-11-04 Isis Pharmaceuticals, Inc. Carbocyclic bicyclic nucleic acid analogs
EP2176280B2 (en) 2007-07-05 2015-06-24 Isis Pharmaceuticals, Inc. 6-disubstituted bicyclic nucleic acid analogs
WO2009067647A1 (en) 2007-11-21 2009-05-28 Isis Pharmaceuticals, Inc. Carbocyclic alpha-l-bicyclic nucleic acid analogs
WO2010048585A2 (en) * 2008-10-24 2010-04-29 Isis Pharmaceuticals, Inc. Oligomeric compounds and methods
EP2370450A1 (en) 2008-11-27 2011-10-05 Roche Diagnostics GmbH Directed synthesis of oligophosphoramidate stereoisomers
WO2011133871A2 (en) 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. 5'-end derivatives
EP3091027B1 (en) 2010-04-28 2018-01-17 Ionis Pharmaceuticals, Inc. 5' modified nucleosides and oligomeric compounds prepared therefrom
EP2601204B1 (en) 2010-04-28 2016-09-07 Ionis Pharmaceuticals, Inc. Modified nucleosides and oligomeric compounds prepared therefrom
US10202599B2 (en) * 2011-08-11 2019-02-12 Ionis Pharmaceuticals, Inc. Selective antisense compounds and uses thereof
MY167390A (en) 2011-11-18 2018-08-16 Alnylam Pharmaceuticals Inc Rnai agents, compositions and methods of use thereof for treating transthyretin (ttr) associated diseases
US9382581B2 (en) 2012-12-13 2016-07-05 Roche Molecular Systems, Inc. Primers with modified phosphate and base in allele-specific PCR
CA2921162A1 (en) 2013-05-01 2014-11-06 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
JP6694382B2 (ja) * 2013-06-21 2020-05-13 アイオーニス ファーマシューティカルズ， インコーポレーテッドＩｏｎｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． 標的核酸を調節するための組成物および方法
IL316808A (en) 2014-08-20 2025-01-01 Alnylam Pharmaceuticals Inc Modified double-stranded RNA materials and their uses
RU2708237C2 (ru) 2014-08-22 2019-12-05 Общество с ограниченной ответственностью "НооГен" Модифицированные олигонуклеотиды и способ их получения
KR102645243B1 (ko) 2016-11-23 2024-03-11 알닐람 파마슈티칼스 인코포레이티드 표적외 효과가 감소된 변형 rna 작용제
CN111226114A (zh) * 2017-10-13 2020-06-02 罗氏创新中心哥本哈根有限公司 用部分立体限定的寡核苷酸子文库鉴定反义寡核苷酸改进的立体限定硫代磷酸酯寡核苷酸变体的方法
CA3090901A1 (en) 2018-02-12 2019-08-15 Ionis Pharmaceuticals, Inc. Modified compounds and uses thereof
KR102857148B1 (ko) 2018-04-05 2025-09-11 사일런스 테라퓨틱스 게엠베하 안티센스 가닥의 5' 단부에 비닐포스포네이트를 갖는 siRNA
IL277889B2 (en) 2018-04-12 2025-01-01 Wave Life Sciences Ltd Oligonucleotide preparations and methods of using them
EP3790970A1 (en) 2018-05-07 2021-03-17 Alnylam Pharmaceuticals Inc. Extrahepatic delivery
US20220064636A1 (en) 2018-10-05 2022-03-03 Ionis Pharmaceuticals, Inc. Modified oligomeric compounds and uses thereof
EP3918073A4 (en) 2019-01-29 2023-11-22 Ionis Pharmaceuticals, Inc. COMPOUNDS AND METHODS FOR REDUCING APP EXPRESSION
KR20220062517A (ko) 2019-08-15 2022-05-17 아이오니스 파마수티컬즈, 인코포레이티드 결합 변형된 올리고머 화합물 및 이의 용도
EP4013428A4 (en) 2019-08-15 2023-08-09 Ionis Pharmaceuticals, Inc. MODIFIED OLIGOMER COMPOUNDS AND USES THEREOF
AU2020378414A1 (en) 2019-11-06 2022-05-26 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
KR20230043914A (ko) 2020-07-28 2023-03-31 아이오니스 파마수티컬즈, 인코포레이티드 App 발현을 감소시키기 위한 화합물 및 방법
WO2022174053A1 (en) 2021-02-11 2022-08-18 Ionis Pharmaceuticals, Inc. Linkage modified oligomeric compounds and uses thereof
CN117480254A (zh) 2021-06-30 2024-01-30 Ionis制药公司 合成键修饰的寡聚化合物的方法
US20240360448A1 (en) 2021-08-18 2024-10-31 Ionis Pharmaceuticals, Inc. Linkage modified oligomeric compounds and uses thereof
IL322549A (en) 2023-02-17 2025-10-01 Ionis Pharmaceuticals Inc Compounds and methods for reducing expression of applications
WO2024173783A2 (en) 2023-02-17 2024-08-22 Ionis Pharmaceuticals, Inc. Allele-selective compounds and methods for modulating huntingtin expression
IL322701A (en) 2023-02-17 2025-10-01 Ionis Pharmaceuticals Inc Compounds and methods for regulating alpha-synuclein expression

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009516521A (ja) 2005-11-23 2009-04-23 エフ．ホフマン−ラ ロシュ アーゲー リン酸塩模倣物を含むポリヌクレオチド
JP2010524874A (ja) 2007-04-18 2010-07-22 エフ．ホフマン−ラ ロシュ アーゲー α−リン酸擬似体を有するヌクレオチド
WO2018156056A1 (ru) 2017-02-21 2018-08-30 Дмитрий Александрович СТЕЦЕНКО Модифицированные олигонуклеотиды, активирующие рнказу н

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Chemistry - An Asian Journal，2019年01月02日，Vol.14(8)，p.1212-1220
Russian Journal of Bioorganic Chemistry，2017年，Vol.43(1)，p.38-42
Russian Journal of Bioorganic Chemistry，2017年，Vol.43(6)，p.664-668

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