Title:
METHOD FOR REDUCING TOXICITY OF ANTISENSE NUCLEIC ACIDS
Document Type and Number:
WIPO Patent Application WO/2021/107143
Kind Code:
A1
Abstract:
The purpose of the present invention is to reduce the strong hepatotoxicity of antisense nucleic acids that incorporate an artificial nucleobase (e.g., LNA). The present invention provides a bridged antisense nucleic acid for which antisense nucleic acid-induced toxicity is reduced by the supplemental addition to the wing region of a specific artificial nucleobase (e.g., MCA), while retaining the sequence of the antisense nucleic acid and the number of artificial nucleobases (e.g., LNA). The present invention also provides an antisense nucleic acid drug having a remarkably-reduced hepatotoxicity.
Inventors:
SEIO KOHJI (JP)
MASAKI YOSHIAKI (JP)
TOMORI TAKAHITO (JP)
MASAKI YOSHIAKI (JP)
TOMORI TAKAHITO (JP)
Application Number:
PCT/JP2020/044370
Publication Date:
June 03, 2021
Filing Date:
November 27, 2020
Export Citation:
Assignee:
TOKYO INST TECH (JP)
International Classes:
C12N15/113; A61K31/7125; A61K48/00; A61P43/00; C07H21/04
Domestic Patent References:
| WO2017142054A1 | 2017-08-24 | |||
| WO2007102581A1 | 2007-09-13 | |||
| WO2019182037A1 | 2019-09-26 | |||
| WO2018155450A1 | 2018-08-30 |
Foreign References:
| JP2010507579A | 2010-03-11 | |||
| JP2016509837A | 2016-04-04 | |||
| JP2013518605A | 2013-05-23 |
Other References:
YAMADA, T. ET AL.: "Synthesis of 2'-0-[2-(N- methylcarbamoyl)ethyl]ribonucleosides using oxa- michael reaction and chemical and biological properties of oligonucleotide derivatives incorporating these modified ribonucleosides", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 76, 2011, pages 3042 - 3053, XP055621126, DOI: 10.1021/jo101963z
ZHAO, Q. ET AL., ANTISENSE RES. DEV., vol. 3, 2009, pages 53 - 66
AGRAWAL S., TRENDS BIOTECHNOL., vol. 14, 1996, pages 376 - 87
EUROPEAN MEDICINES AGENCY, EMA/792736/2012, EMEA/H/C/002429, Retrieved from the Internet
W. BRAD WANPUNIT P. SETH, J. MED. CHEM., vol. 59, 2016, pages 9645 - 9667
MASAKI, Y. ET AL., NUCLEIC ACID THERAPEUTICS, vol. 28, 2018, pages 307 - 311
COLIN B. REESEHONGBIN YAN: "J. Chem. Soc.", vol. 1, 2002, PERKIN TRANS, pages: 2619 - 2633
ZHAO, Q. ET AL., ANTISENSE RES. DEV., vol. 3, 2009, pages 53 - 66
AGRAWAL S., TRENDS BIOTECHNOL., vol. 14, 1996, pages 376 - 87
EUROPEAN MEDICINES AGENCY, EMA/792736/2012, EMEA/H/C/002429, Retrieved from the Internet
W. BRAD WANPUNIT P. SETH, J. MED. CHEM., vol. 59, 2016, pages 9645 - 9667
MASAKI, Y. ET AL., NUCLEIC ACID THERAPEUTICS, vol. 28, 2018, pages 307 - 311
COLIN B. REESEHONGBIN YAN: "J. Chem. Soc.", vol. 1, 2002, PERKIN TRANS, pages: 2619 - 2633
Attorney, Agent or Firm:
AOKI, Atsushi et al. (JP)
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