Title:
MICROMOLECULAR DRUG-OLIGONUCLEOTIDE CONJUGATE AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2023/246827
Kind Code:
A1
Abstract:
The present invention relates to the technical field of biological medicines, and particularly, to a micromolecular drug-oligonucleotide conjugate and use thereof. The present invention solves the problems of poor water solubility and difficulty in drug delivery of existing micromolecular immunomodulatory drugs by conjugating an oligonucleotide with the drug. The excellent hydrophilicity of oligonucleotide can improve the solubility and the in-vivo tissue distribution of the micromolecular drug and promote delivery and absorption. The hydrophobic micromolecular drug can in turn promote the endocytosis of the oligonucleotide, thus improving the regulation capability of the oligonucleotide on the target gene. In addition, by means of the co-delivery of the micromolecular drug and the functional oligonucleotide molecule, the present invention achieves the synergetic regulation of different targets of an inflammatory response, thus achieving a better therapeutic effect and safe and efficient medication.
Inventors:
ZHANG CHUAN (CN)
ZHU RUIHUA (CN)
HUANG YANGYANG (CN)
ZHU RUIHUA (CN)
HUANG YANGYANG (CN)
Application Number:
PCT/CN2023/101555
Publication Date:
December 28, 2023
Filing Date:
June 21, 2023
Export Citation:
Assignee:
UNIV SHANGHAI JIAOTONG (CN)
ZHEJIANG YIMOU BIOLOGY SCIENCE AND TECH CO LTD (CN)
ZHEJIANG YIMOU BIOLOGY SCIENCE AND TECH CO LTD (CN)
International Classes:
A61K47/55; A61K31/436; A61K31/7105; A61K31/713; A61K38/13; A61K45/06; A61K47/26; A61K47/54; A61P1/00; A61P17/00; A61P17/06; A61P19/02; A61P27/02; A61P29/00; A61P37/08; C12N15/11; C12N15/113
Domestic Patent References:
| WO2018130583A1 | 2018-07-19 |
Foreign References:
| CN115282283A | 2022-11-04 | |||
| CN104244987A | 2014-12-24 | |||
| US20190345495A1 | 2019-11-14 | |||
| CN111803517A | 2020-10-23 | |||
| CN109568595A | 2019-04-05 |
Other References:
GUO YUANYUAN, QIN JINGCAN, ZHAO QIANQIAN, YANG JIAPEI, WEI XIAOER, HUANG YU, XIE MIAO, ZHANG CHUAN, LI YUEHUA: "Plaque‐Targeted Rapamycin Spherical Nucleic Acids for Synergistic Atherosclerosis Treatment", ADVANCED SCIENCE, vol. 9, no. 16, 1 May 2022 (2022-05-01), XP093118675, ISSN: 2198-3844, DOI: 10.1002/advs.202105875
JOHANNES WINKLER: "Oligonucleotide conjugates for therapeutic applications", THERAPEUTIC DELIVERY, FUTURE SCIENCE LTD., GB, vol. 4, no. 7, 1 July 2013 (2013-07-01), GB , pages 791 - 809, XP055238333, ISSN: 2041-5990, DOI: 10.4155/tde.13.47
MANDAL ABHIRUP, KUMBHOJKAR NINAD, REILLY CHARLES, DHARAMDASANI VIMISHA, UKIDVE ANVAY, INGBER DONALD E., MITRAGOTRI SAMIR: "Treatment of psoriasis with NFKBIZ siRNA using topical ionic liquid formulations", SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE, US, vol. 6, no. 30, 22 July 2020 (2020-07-22), US , pages eabb6049, XP055779233, ISSN: 0036-8075, DOI: 10.1126/sciadv.abb6049
PANKRATZ FRANZISKA, HOHNLOSER CATHERINE, BEMTGEN XAVIER, JAENICH CATERINA, KREUZALER SHEENA, HOEFER IMO, PASTERKAMP GERARD, MASTRO: "MicroRNA-100 Suppresses Chronic Vascular Inflammation by Stimulation of Endothelial Autophagy", CIRCULATION RESEARCH, GRUNDE AND STRATTON , BALTIMORE, US, vol. 122, no. 3, 2 February 2018 (2018-02-02), US , pages 417 - 432, XP093118677, ISSN: 0009-7330, DOI: 10.1161/CIRCRESAHA.117.311428
JOHANNES WINKLER: "Oligonucleotide conjugates for therapeutic applications", THERAPEUTIC DELIVERY, FUTURE SCIENCE LTD., GB, vol. 4, no. 7, 1 July 2013 (2013-07-01), GB , pages 791 - 809, XP055238333, ISSN: 2041-5990, DOI: 10.4155/tde.13.47
MANDAL ABHIRUP, KUMBHOJKAR NINAD, REILLY CHARLES, DHARAMDASANI VIMISHA, UKIDVE ANVAY, INGBER DONALD E., MITRAGOTRI SAMIR: "Treatment of psoriasis with NFKBIZ siRNA using topical ionic liquid formulations", SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE, US, vol. 6, no. 30, 22 July 2020 (2020-07-22), US , pages eabb6049, XP055779233, ISSN: 0036-8075, DOI: 10.1126/sciadv.abb6049
PANKRATZ FRANZISKA, HOHNLOSER CATHERINE, BEMTGEN XAVIER, JAENICH CATERINA, KREUZALER SHEENA, HOEFER IMO, PASTERKAMP GERARD, MASTRO: "MicroRNA-100 Suppresses Chronic Vascular Inflammation by Stimulation of Endothelial Autophagy", CIRCULATION RESEARCH, GRUNDE AND STRATTON , BALTIMORE, US, vol. 122, no. 3, 2 February 2018 (2018-02-02), US , pages 417 - 432, XP093118677, ISSN: 0009-7330, DOI: 10.1161/CIRCRESAHA.117.311428
Attorney, Agent or Firm:
BEIJING FINELAND IP FIRM (CN)
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