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)
  • Zoology (AREA)
  • 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 (enExample)
EP (1) EP3475292B1 (enExample)
JP (1) JP7235512B2 (enExample)
KR (2) KR102722183B1 (enExample)
CN (1) CN109689668B (enExample)
ES (1) ES2999138T3 (enExample)
WO (1) WO2017223258A1 (enExample)

Families Citing this family (10)

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Publication number Priority date Publication date Assignee Title
WO2016040748A1 (en) 2014-09-12 2016-03-17 Ionis Pharmaceuticals, Inc. Compositions and methods for detection of smn protein in a subject and treatment of a subject
SMT202100701T1 (it) 2017-07-10 2022-01-10 Geron Corp Processo migliorato per preparare imetelstat
CN114072501A (zh) 2019-05-06 2022-02-18 马萨诸塞大学 抗c9orf72寡核苷酸及相关方法
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
BR112022016238A2 (pt) 2020-02-28 2022-10-11 Ionis Pharmaceuticals Inc Compostos e métodos para modular smn2
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
WO2024061842A1 (en) 2022-09-19 2024-03-28 Bachem Holding Ag Improved oligonucleotide synthesis
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
WO2025235761A1 (en) 2024-05-09 2025-11-13 Biogen Ma Inc. Reagents and processes for preparing oligonucleotides

Citations (1)

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Publication number Priority date Publication date Assignee Title
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
DK1910395T3 (da) 2005-06-23 2013-02-04 Isis Pharmaceuticals Inc Sammensætninger og fremgangsmåder til modulation af SMN2-splejsning
SI3305302T1 (sl) 2009-06-17 2018-12-31 Biogen Ma Inc. Sestave in metode za modulacijo združevanja smn2 pri subjektu
US8642755B2 (en) * 2009-06-30 2014-02-04 Agilent Technologies, Inc. Use of thioacetic acid derivatives in the sulfurization of oligonucleotides with phenylacetyl disulfide
US9725716B2 (en) * 2011-12-06 2017-08-08 Ohio State Innovation Foundation and Research Institute at Nationwide Children's Hospital 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
SG11201608109TA (en) 2014-04-01 2016-10-28 Ionis Pharmaceuticals Inc Compositions for modulating sod-1 expression
PE20171448A1 (es) * 2015-03-10 2017-10-02 Aduro Biotech Inc Composiciones y metodos para activar la senalizacion dependiente del estimulador del gen de interferon
JOP20190218A1 (ar) * 2017-03-22 2019-09-22 Boehringer Ingelheim Int مركبات ثنائية النيوكليوتيدات حلقية معدلة

Patent Citations (1)

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

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