Title:
USE OF MODIFIED GLP-1 ANALOGUE DIMERS OF DIFFERENT CONFIGURATIONS AND PREPARATION METHOD THEREFOR IN TREATING TYPE 2 DIABETES
Document Type and Number:
WIPO Patent Application WO/2021/068986
Kind Code:
A1
Abstract:
Provided in the present invention is a use of novel GLP-1 fatty acid-modified or non-modified dimers of different configurations for a pancreas protecting or glucose reducing effect in treating type 2 diabetes. The dimers of the present invention are formed from a disulfide bond formed by means of cysteine oxidation in two same cysteine-containing GLP-1 monomers. An H-type GLP-1 homodimer of the present invention (having a disulfide bond formed inside the peptide chain), without reducing activity, markedly increases the glucose reduction duration of the GLP-1 dimer. The duration of activity of the provided GLP-1 analog dimer in vivo reaches 19 days, a marked extension relative to the in vivo activity of 3 days of positive control drug Liraglutide, or currently reported long-acting GLP-1 analogues, greatly advancing the technical progress of long-acting GLP-1 drugs and facilitating the clinical application and popularization thereof. Meanwhile, a U-type homodimer (having a disulfide bond formed at the C-terminus of the peptide chain) has no impact on blood glucose, but can clearly protect pancreas exocrine cells such as in acini and ducts.
Inventors:
TANG SONGSHAN (CN)
ZHANG XUDONG (CN)
LUO QUN (CN)
TANG JINGXUAN (CN)
YANG LI (CN)
TAN HONGMEI (CN)
ZHANG XUDONG (CN)
LUO QUN (CN)
TANG JINGXUAN (CN)
YANG LI (CN)
TAN HONGMEI (CN)
Application Number:
PCT/CN2020/127422
Publication Date:
April 15, 2021
Filing Date:
November 09, 2020
Export Citation:
Assignee:
NANJING FINEPEPTIDE BIOPHARMACEUTICAL CO LTD (CN)
International Classes:
C07K14/605; A61K38/26; A61P3/10; C07K19/00
Foreign References:
| CN110845601A | 2020-02-28 | |||
| CN108025041A | 2018-05-11 | |||
| CN102718858A | 2012-10-10 |
Other References:
CAI XINGGUANG, SUN LIDAN, DAI YUXUAN, AVRAHAM YOSEFA, LIU CHUNXIA, HAN JING, LIU YUAN, FENG DAZHI, HUANG WENLONG, QIAN HAI: "Novel fatty acid chain modified GLP-1 derivatives with prolonged in vivo glucose-lowering ability and balanced glucoregulatory activity", BIOORGANIC & MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 26, no. 9, 1 May 2018 (2018-05-01), AMSTERDAM, NL, pages 2599 - 2609, XP055798899, ISSN: 0968-0896, DOI: 10.1016/j.bmc.2018.04.022
Attorney, Agent or Firm:
GUANGZHOU KEYUE I.P. LAW OFFICE (CN)
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