WO2017130151A1 - 5'-phosphorothiolate mrna 5'-end (cap) analogs, mrna comprising the same, method of obtaining and uses thereof - Google Patents

5'-phosphorothiolate mrna 5'-end (cap) analogs, mrna comprising the same, method of obtaining and uses thereof Download PDF

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Publication number
WO2017130151A1
WO2017130151A1 PCT/IB2017/050447 IB2017050447W WO2017130151A1 WO 2017130151 A1 WO2017130151 A1 WO 2017130151A1 IB 2017050447 W IB2017050447 W IB 2017050447W WO 2017130151 A1 WO2017130151 A1 WO 2017130151A1
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WO
WIPO (PCT)
Prior art keywords
formula
group
mrna
independently selected
alkyl
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.)
Ceased
Application number
PCT/IB2017/050447
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English (en)
French (fr)
Inventor
Jacek Jemielity
Kaja FAC-DĄBROWSKA
Błażej WOJTCZAK
Marek Baranowski
Anna NOWICKA
Joanna Kowalska
Paweł SIKORSKI
Marcin WARMIŃSKI
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Uniwersytet Warszawski
Original Assignee
Uniwersytet Warszawski
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 Uniwersytet Warszawski filed Critical Uniwersytet Warszawski
Priority to JP2018537845A priority Critical patent/JP7144050B2/ja
Priority to EA201891429A priority patent/EA038834B1/ru
Priority to KR1020187021714A priority patent/KR102742219B1/ko
Priority to ES17712541T priority patent/ES2879802T3/es
Priority to US16/073,499 priority patent/US11066436B2/en
Priority to CA3011663A priority patent/CA3011663C/en
Priority to CN201780013350.3A priority patent/CN109071589A/zh
Priority to AU2017211693A priority patent/AU2017211693B2/en
Priority to PL17712541T priority patent/PL3408276T3/pl
Priority to EP17712541.6A priority patent/EP3408276B1/en
Publication of WO2017130151A1 publication Critical patent/WO2017130151A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C07H1/02—Phosphorylation
    • C07H1/04—Introducing polyphosphoric acid radicals
    • 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

Definitions

  • the present invention additionally relates to a method of preparation of compound according to formula 1 , said method comprising: steps wherein a 5'-iodonucleoside according to formula 8
  • Yi and Y 2 are independently selected from the group comprising CH 2 , CHCI, CCI 2 , CHF, CF 2 , NH, and O;
  • Xi and X 2 are independently selected from a group comprising O, S;
  • R 1 is selected from a group comprising CH 3 , C 2 H 5 , CH 2 Ph, alkyl, or substituted alkyl;
  • R 2 and R 3 are independently selected from a group comprising H, OH, OCH 3 , OC 2 H 5 ' - COOH, N 3 , alkyl, or substituted alkyl;
  • cap analogs were then tested as substrates of the human enzyme DcpS (hDcpS). As determined by using reverse phase HPLC (RP HPLC), only four of the analogs: m 7 GppSG (no. 21 ), m 7 GpppSG (no. 22) m 7 , 2' °GpppSG (no. 38) and m 7 Gpp s pSG D1 /D2 (no. 35 - 36) are hydrolyzed by DcpS. Other analogs containing sulfur atom at the 5 ' position from the side of the 7-methylated guanosine are resistant to hydrolysis by hDcpS (stability comparison of two different analogs (no. 22) and (no.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
PCT/IB2017/050447 2016-01-29 2017-01-27 5'-phosphorothiolate mrna 5'-end (cap) analogs, mrna comprising the same, method of obtaining and uses thereof Ceased WO2017130151A1 (en)

Priority Applications (10)

Application Number Priority Date Filing Date Title
JP2018537845A JP7144050B2 (ja) 2016-01-29 2017-01-27 ５’－ホスホロチオラート ｍＲＮＡ ５’－末端（キャップ）類似体、それを含むｍＲＮＡ、それらを得る方法およびそれらの使用方法
EA201891429A EA038834B1 (ru) 2016-01-29 2017-01-27 5'-фосфоротиоатные аналоги 5'-конца (кэпа) мрнк, содержащая их мрнк, способ их получения и применение
KR1020187021714A KR102742219B1 (ko) 2016-01-29 2017-01-27 5'-포스포로티올레이트 mRNA 5'-말단 (캡) 유사체, 이를 포함하는 mRNA, 이를 얻기 위한 방법, 및 이의 용도
ES17712541T ES2879802T3 (es) 2016-01-29 2017-01-27 Análogos de extremo 5' (caperuza) de ARNm 5'-fosforotiolato, ARNm que comprende los mismos, método de obtención y usos de los mismos
US16/073,499 US11066436B2 (en) 2016-01-29 2017-01-27 5′-phosphorothiolate mRNA 5′-end (cap) analogs, mRNA comprising the same, method of obtaining and uses thereof
CA3011663A CA3011663C (en) 2016-01-29 2017-01-27 5'-phosphorothiolate mrna 5'-end (cap) analogs, mrna comprising the same, method of obtaining and uses thereof
CN201780013350.3A CN109071589A (zh) 2016-01-29 2017-01-27 5′-硫代磷酸酯mRNA 5′-端(帽)类似物、包含所述类似物的mRNA、其获得方法和用途
AU2017211693A AU2017211693B2 (en) 2016-01-29 2017-01-27 5'-phosphorothiolate mRNA 5'-end (cap) analogs, mRNA comprising the same, method of obtaining and uses thereof
PL17712541T PL3408276T3 (pl) 2016-01-29 2017-01-27 5’-tiofosforanowe analogi końca 5’ mRNA (kapu), mRNA je zawierające, sposób ich otrzymywania i zastosowania
EP17712541.6A EP3408276B1 (en) 2016-01-29 2017-01-27 5'-phosphorothiolate mrna 5'-end (cap) analogs, mrna comprising the same, method of obtaining and uses thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
PLPL415967 2016-01-29
PL415967A PL415967A1 (pl) 2016-01-29 2016-01-29 5'-tiofosforanowe analogi końca 5' mRNA (kapu), sposób ich otrzymywania i zastosowanie

Publications (1)

Publication Number Publication Date
WO2017130151A1 true WO2017130151A1 (en) 2017-08-03

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PCT/IB2017/050447 Ceased WO2017130151A1 (en) 2016-01-29 2017-01-27 5'-phosphorothiolate mrna 5'-end (cap) analogs, mrna comprising the same, method of obtaining and uses thereof

Country Status (11)

Country Link
US (1) US11066436B2 (enExample)
EP (1) EP3408276B1 (enExample)
JP (1) JP7144050B2 (enExample)
KR (1) KR102742219B1 (enExample)
CN (1) CN109071589A (enExample)
AU (1) AU2017211693B2 (enExample)
CA (1) CA3011663C (enExample)
EA (1) EA038834B1 (enExample)
ES (1) ES2879802T3 (enExample)
PL (2) PL415967A1 (enExample)
WO (1) WO2017130151A1 (enExample)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020231697A1 (en) * 2019-05-10 2020-11-19 New England Biolabs, Inc. Chemical capping for template switching
US20230295215A1 (en) * 2020-02-12 2023-09-21 Uniwersytet Warszawski Novel mrna 5'-end cap analogs modified within phosphate residues, rna molecule incorporating the same, uses thereof and method of synthesizing rna molecule or peptide
EP4464713A1 (en) 2023-05-18 2024-11-20 Siec Badawcza Lukasiewicz - PORT Polski Osrodek Rozwoju Technologii Circular rna analogs, preparation and application thereof

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110907358B (zh) * 2019-12-09 2022-08-30 福建师范大学 一种光微流微泡腔铅离子传感器的实现装置及方法
CN113278665A (zh) * 2020-08-20 2021-08-20 深圳市瑞吉生物科技有限公司 一种Cap2结构5′帽子类似物及其制备方法和应用
WO2022051677A1 (en) 2020-09-04 2022-03-10 Verve Therapeutics, Inc. Compositions and methods for capping rnas
CN119137271A (zh) * 2022-03-01 2024-12-13 维乎医疗有限公司 用于加帽rna的组合物和方法
CN114685588B (zh) * 2022-05-05 2024-03-29 江苏申基生物科技有限公司 一种含开环核苷结构的起始加帽寡核苷酸引物
CN116143855B (zh) * 2022-11-08 2023-11-28 江苏申基生物科技有限公司 一种乙烯基膦酸修饰的mRNA帽类似物及其制备方法和应用

Citations (3)

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WO2008157688A2 (en) * 2007-06-19 2008-12-24 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Synthesis and use of anti-reverse phosphorothioate analogs of the messenger rna cap
WO2009149253A2 (en) * 2008-06-06 2009-12-10 Uniwersytet Warszawski Mrna cap analogs
EP2281579A1 (en) * 2009-08-05 2011-02-09 BioNTech AG Vaccine composition comprising 5'-Cap modified RNA

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JP2008546424A (ja) * 2005-06-28 2008-12-25 アジェンコート パーソナル ジェノミクス コーポレイション 修飾ポリヌクレオチドを作製する方法および配列決定する方法
JP6567494B2 (ja) * 2013-03-14 2019-08-28 シャイアー ヒューマン ジェネティック セラピーズ インコーポレイテッド ４’−チオ−修飾ヌクレオチドを有するリボ核酸及び関連方法
RS59991B1 (sr) * 2013-08-08 2020-04-30 Scripps Research Inst Metoda enzimskog in vitro obeležavanja specifičnog za položaj nukleinskih kiselina uvođenjem neprirodnih nukleotida

Patent Citations (3)

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Publication number Priority date Publication date Assignee Title
WO2008157688A2 (en) * 2007-06-19 2008-12-24 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Synthesis and use of anti-reverse phosphorothioate analogs of the messenger rna cap
WO2009149253A2 (en) * 2008-06-06 2009-12-10 Uniwersytet Warszawski Mrna cap analogs
EP2281579A1 (en) * 2009-08-05 2011-02-09 BioNTech AG Vaccine composition comprising 5'-Cap modified RNA

Non-Patent Citations (2)

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Title
ANNA WYPIJEWSKA DEL NOGAL ET AL: "Analysis of decapping scavenger cap complex using modified cap analogs reveals molecular determinants for efficient cap binding", FEBS JOURNAL, vol. 280, no. 24, 23 December 2013 (2013-12-23), GB, pages 6508 - 6527, XP055367414, ISSN: 1742-464X, DOI: 10.1111/febs.12553 *
KOWALSKA JOANNA ET AL: "Synthesis and characterization of mRNA cap analogs containing phosphorothioate substitutions that bind tightly to eIF4E and are resistant to the decapping pyrophosphatase DcpS", RNA, COLD SPRING HARBOR LABORATORY PRESS, US, vol. 14, no. 6, 1 June 2008 (2008-06-01), pages 1119 - 1131, XP002554206, ISSN: 1355-8382, DOI: 10.1261/RNA.990208 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020231697A1 (en) * 2019-05-10 2020-11-19 New England Biolabs, Inc. Chemical capping for template switching
GB2597423A (en) * 2019-05-10 2022-01-26 New England Biolabs Inc Chemical capping for template switching
GB2597423B (en) * 2019-05-10 2024-08-14 New England Biolabs Inc Chemical capping for template switching
US20230295215A1 (en) * 2020-02-12 2023-09-21 Uniwersytet Warszawski Novel mrna 5'-end cap analogs modified within phosphate residues, rna molecule incorporating the same, uses thereof and method of synthesizing rna molecule or peptide
EP4464713A1 (en) 2023-05-18 2024-11-20 Siec Badawcza Lukasiewicz - PORT Polski Osrodek Rozwoju Technologii Circular rna analogs, preparation and application thereof
WO2024236203A1 (en) 2023-05-18 2024-11-21 Sieć Badawcza Łukasiewicz Port Polski Ośrodek Rozwoju Technologii Circular rna analogs comprising 7-methylguanosine cap, preparation, and application thereof
WO2024236202A1 (en) 2023-05-18 2024-11-21 Sieć Badawcza Łukasiewicz Port Polski Ośrodek Rozwoju Technologii Circular rna analogs, preparation and application thereof

Also Published As

Publication number Publication date
KR102742219B1 (ko) 2024-12-13
EP3408276A1 (en) 2018-12-05
CN109071589A (zh) 2018-12-21
CA3011663C (en) 2023-10-31
ES2879802T3 (es) 2021-11-23
JP7144050B2 (ja) 2022-09-29
CA3011663A1 (en) 2017-08-03
AU2017211693B2 (en) 2021-09-09
JP2019504837A (ja) 2019-02-21
US20190300563A1 (en) 2019-10-03
AU2017211693A1 (en) 2018-08-09
KR20180100595A (ko) 2018-09-11
EP3408276B1 (en) 2021-04-07
PL3408276T3 (pl) 2021-10-25
EA201891429A1 (ru) 2019-02-28
PL415967A1 (pl) 2017-07-31
US11066436B2 (en) 2021-07-20
EA038834B1 (ru) 2021-10-26

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