Title:
ANTISENSE NUCLEIC ACID GLYCOSYL CONJUGATE, PREPARATION METHOD THEREFOR, AND USE THEREOF IN LIVER CANCER TREATMENT
Document Type and Number:
WIPO Patent Application WO/2024/067500
Kind Code:
A1
Abstract:
Provided is an antisense nucleic acid glycosyl conjugate, which is formed by covalently conjugating a sugar molecule to the 5' end of an antisense nucleic acid by means of a linker arm. In-vitro pharmacodynamics show that the anti-tumor cell proliferation activity and the target gene silencing activity of various conjugates are comparable to those of non-conjugated antisense nucleic acid chains. After conjugation, the drug uptake rate is improved, demonstrating higher in-vivo liver cancer inhibitory activity. Glu-CT102MOE5 shows the most significant effect. The in-vitro and in-vivo activities of antisense nucleic acids PHN02 and PHN07 are superior to those of CT102. After further chemical modification, the anti-tumor ability of PHN02MOE5 is comparable to that of CT102MOE5. The antisense nucleic acid glycosyl conjugate can be used for the treatment of liver cancer.
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Inventors:
YANG ZHENJUN (CN)
PAN YUFEI (CN)
GUAN JING (CN)
PAN YUFEI (CN)
GUAN JING (CN)
Application Number:
PCT/CN2023/121152
Publication Date:
April 04, 2024
Filing Date:
September 25, 2023
Export Citation:
Assignee:
UNIV BEIJING (CN)
HAPHARM BEIJING BIOTECHNOLOGY CO LTD (CN)
HAPHARM BEIJING BIOTECHNOLOGY CO LTD (CN)
International Classes:
A61K47/54; A61K31/7088; A61K47/20; A61K47/22; A61K47/24; A61P35/00
Domestic Patent References:
| WO2017015109A1 | 2017-01-26 |
Foreign References:
| CN115487308A | 2022-12-20 | |||
| CN115851738A | 2023-03-28 | |||
| CN114246829A | 2022-03-29 | |||
| CN105722980A | 2016-06-29 | |||
| CN110621700A | 2019-12-27 |
Other References:
YUFEI PAN: "Modified ASO conjugates encapsulated with cytidinyl/cationic lipids exhibit more potent and longer-lasting anti-HCC effects", MOLECULAR THERAPY-NUCLEIC ACIDS, CELL PRESS, US, vol. 32, 1 June 2023 (2023-06-01), US , pages 807 - 821, XP093152287, ISSN: 2162-2531, DOI: 10.1016/j.omtn.2023.04.028
SPRINGER, A. D.; DOWDY, S. F.: "GalNAc-siRNA conjugates: leading the way for delivery of RNAi therapeutics", NUCLEIC ACID THERAPEUTICS, vol. 28, no. 3, 30 June 2018 (2018-06-30), XP055555952, ISSN: 2159-3345, DOI: 10.1089/nat.2018.0736
SUN, JING; YANG, ZHENJUN: "Recent Progress on SiRNA Conjugates", ZHONGGUO KEXUE. HUAXUE - SCIENTIA SINICA CHIMICA, ZHONGGUO KEXUE ZAZHISHE, CN, vol. 46, no. 07, 20 July 2016 (2016-07-20), CN , pages 633 - 642, XP009553460, ISSN: 1674-7224
SPRINGER, A. D.; DOWDY, S. F.: "GalNAc-siRNA conjugates: leading the way for delivery of RNAi therapeutics", NUCLEIC ACID THERAPEUTICS, vol. 28, no. 3, 30 June 2018 (2018-06-30), XP055555952, ISSN: 2159-3345, DOI: 10.1089/nat.2018.0736
SUN, JING; YANG, ZHENJUN: "Recent Progress on SiRNA Conjugates", ZHONGGUO KEXUE. HUAXUE - SCIENTIA SINICA CHIMICA, ZHONGGUO KEXUE ZAZHISHE, CN, vol. 46, no. 07, 20 July 2016 (2016-07-20), CN , pages 633 - 642, XP009553460, ISSN: 1674-7224
Attorney, Agent or Firm:
KELONG INTERNATIONAL INTELLECTUAL PROPERTY AGENT LTD. (CN)
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