CN109689668B - 无加帽步骤的硫醇化寡核苷酸的合成 - Google Patents

无加帽步骤的硫醇化寡核苷酸的合成 Download PDF

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CN109689668B
CN109689668B CN201780051170.4A CN201780051170A CN109689668B CN 109689668 B CN109689668 B CN 109689668B CN 201780051170 A CN201780051170 A CN 201780051170A CN 109689668 B CN109689668 B CN 109689668B
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formula
compound
agent
steps
oligonucleotide
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CN109689668A (zh
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石向林
杨纪民
W·F·吉斯曼
Y·费尔伦
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Biogen MA Inc
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Biogen MA Inc
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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
    • C07H21/04—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 deoxyribosyl as saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • 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
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/341—Gapmers, i.e. of the type ===---===
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
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  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Saccharide Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
CN201780051170.4A 2016-06-24 2017-06-22 无加帽步骤的硫醇化寡核苷酸的合成 Active CN109689668B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662354433P 2016-06-24 2016-06-24
US62/354,433 2016-06-24
PCT/US2017/038643 WO2017223258A1 (en) 2016-06-24 2017-06-22 Synthesis of thiolated oligonucleotides without a capping step

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CN109689668A CN109689668A (zh) 2019-04-26
CN109689668B true CN109689668B (zh) 2023-02-17

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US (1) US11142545B2 (https=)
EP (1) EP3475292B1 (https=)
JP (1) JP7235512B2 (https=)
KR (2) KR102722183B1 (https=)
CN (1) CN109689668B (https=)
ES (1) ES2999138T3 (https=)
WO (1) WO2017223258A1 (https=)

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US10436802B2 (en) 2014-09-12 2019-10-08 Biogen Ma Inc. Methods for treating spinal muscular atrophy
CA3195922A1 (en) 2017-07-10 2019-01-17 Geron Corporation Improved process for preparing imetelstat
US11629347B2 (en) 2019-05-06 2023-04-18 University Of Massachusetts Anti-C9ORF72 oligonucleotides and related methods
CN110468171B (zh) * 2019-09-20 2021-10-29 凯莱英医药集团（天津）股份有限公司 核酸的合成方法
CN120505310A (zh) 2020-02-28 2025-08-19 Ionis制药公司 用于调节smn2的化合物和方法
CN114685572B (zh) * 2022-06-02 2022-08-30 上海百力格生物技术有限公司 用于mgb核酸探针合成的氧化剂组合物及探针的合成方法
US20260001902A1 (en) 2022-09-19 2026-01-01 Bachem Holding Ag Improved oligonucleotide synthesis
WO2025028656A1 (ja) 2023-08-02 2025-02-06 日東電工株式会社 オリゴヌクレオチドを製造する方法
WO2025038661A1 (en) * 2023-08-14 2025-02-20 Arrowhead Pharmaceuticals, Inc. Oligonucleotide synthesis methods
WO2025165064A1 (ko) * 2024-02-02 2025-08-07 에스티팜 주식회사 올리고뉴클레오티드 합성을 위한 개선된 방법
WO2025234897A1 (ru) * 2024-05-07 2025-11-13 Акционерное общество "ГЕНЕРИУМ" Способ получения тиофосфатных олигонуклеотидов для терапевтического применения
WO2025235761A1 (en) 2024-05-09 2025-11-13 Biogen Ma Inc. Reagents and processes for preparing oligonucleotides
WO2026082783A1 (en) 2024-10-17 2026-04-23 F. Hoffmann-La Roche Ag Synthesis of thiolated oligonucleotides without capping and without recirculation of the thiolating agent

Citations (1)

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US6809195B1 (en) * 2000-08-16 2004-10-26 Isis Pharmaceuticals, Inc. Process for the preparation of oligonucleotides

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US6087491A (en) * 1993-01-08 2000-07-11 Hybridon, Inc. Extremely high purity oligonucleotides and methods of synthesizing them using dimer blocks
US5614621A (en) * 1993-07-29 1997-03-25 Isis Pharmaceuticals, Inc. Process for preparing oligonucleotides using silyl-containing diamino phosphorous reagents
EP1386925A1 (en) * 2002-07-31 2004-02-04 Girindus AG Method for preparing oligonucleotides
EP3470072A1 (en) 2005-06-23 2019-04-17 Biogen MA Inc. Compositions and methods for modulation of smn2 splicing
ES2699827T3 (es) 2009-06-17 2019-02-13 Biogen Ma Inc Composiciones y métodos para la modulación de corte y empalme de SMN2 en un sujeto
US8642755B2 (en) * 2009-06-30 2014-02-04 Agilent Technologies, Inc. Use of thioacetic acid derivatives in the sulfurization of oligonucleotides with phenylacetyl disulfide
WO2013086207A1 (en) * 2011-12-06 2013-06-13 The Ohio State University Non-ionic, low osmolar contrast agents for delivery of antisense oligonucleotides and treatment of disease
WO2015061246A1 (en) * 2013-10-21 2015-04-30 Isis Pharmaceuticals, Inc. Method for solution phase detritylation of oligomeric compounds
HUE050704T2 (hu) 2014-04-01 2020-12-28 Biogen Ma Inc Összetételek a SOD-1 expressziójának modulálására
EA035817B1 (ru) * 2015-03-10 2020-08-14 Адуро Байотек, Инк. Композиции и способы для активации сигналинга, зависимого от "гена стимулятора интерферона"
JOP20190218A1 (ar) * 2017-03-22 2019-09-22 Boehringer Ingelheim Int مركبات ثنائية النيوكليوتيدات حلقية معدلة

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US6809195B1 (en) * 2000-08-16 2004-10-26 Isis Pharmaceuticals, Inc. Process for the preparation of oligonucleotides

Non-Patent Citations (3)

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Title
Large-scale synthesis of oligonucleotide phosphorothioates using 3-amino-1,2,4-dithiazole-5-thione as an efficient sulfur-transfer reagent;TANG，ET AL;《ORGANIC PROCESS RESEARCH AND DEVELOPMENT》;20000101;第4卷(第3期);第194-198页 *
SULFURIZING REAGENT II AND ITS USE IN SYNTHESIZING OLIGONUCLEOTIDE PHOSPHOROTHIOATES;Marc M. Lemaître, ET AL;《The Glen Report》;20061231;第18卷(第1期);第1-6页 *
Synthesis of Antisense Oligonucleotides:Replacement of 3H-1,2-Benzodithiol-3-one 1,1-Dioxide(Beaucage Reagent) with Phenylacetyl Disulfide(PADS) As Efficient Sulfurization Reagent: From Bench to Bulk Manufacture of Active Pharmaceutical Ingredient;ZACHARIA S.CHERUUALLATH, ET AL;《ORGANIC PROCESS RESEARCH AND DEVELOPMENT》;20000501;第4卷(第3期);第199-204页 *

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Publication number Publication date
EP3475292B1 (en) 2024-09-18
US11142545B2 (en) 2021-10-12
US20190161513A1 (en) 2019-05-30
EP3475292A1 (en) 2019-05-01
KR20230133947A (ko) 2023-09-19
JP2019518778A (ja) 2019-07-04
CN109689668A (zh) 2019-04-26
WO2017223258A1 (en) 2017-12-28
JP7235512B2 (ja) 2023-03-08
KR20190020743A (ko) 2019-03-04
KR102722183B1 (ko) 2024-10-24
ES2999138T3 (en) 2025-02-24

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