Human fgf21 mutant, preparation method and use thereof

Patent metadata

Field	Value
Publication number	US-2021163560-A1
Application number	US-201816608706-A
Country	US
Kind code	A1
Filing date	Apr 11, 2018
Priority date	Apr 28, 2017
Publication date	Jun 3, 2021
Grant date	—

Abstract

The present disclosure relates to a human FGF21 mutant, a preparation method and a use thereof, and specifically relates to a human fibroblast growth factor 21 (FGF21) mutant, a gene encoding the same, and a method for preparing the mutant and a method of using the mutant for treating type 2 diabetes, obesity, dyslipidemia or metabolic disorders.

First claim

1 . A human FGF21 mutant, comprising the following ammo acid changes relative to an amino acid sequence of wild-type human FGF21 protein:
1) one Cys inserted at a position between Ala at position 31 and His at position 32 of the amino acid sequence of wild type human FGF21 protein, and. Cys substitution(s) for Gly at position 43 and/or Ala at position of 44, 2) Gly substitution for Pro at position 171 in the amino acid sequence of wild type human FGF21 protein; and/or 3) replacement of an amino acid fragment of positions 24 to 31 of the amino acid sequence of wild type human FGF21 protein with an amino acid fragment of 5-15 amino acids, preferably 6-14 amino acids, more preferably 7-13 amino acids, still more preferably 8-10 amino acids, and most preferably 8 amino acids.

2 . The mutant according to claim 1 , wherein the amino acid fragment for the replacement is a fragment of 8 amino acids represented by formula X 1 X 2 X 3 X 4 X 5 X 6 X 7 X 8 , wherein each of X 1 -X 8 is independently selected from any amino acid, preferably X 1 is Ser or Asp, X 2 is Gly or Asp, X 3 is Pro or Ala, X 4 is Ala or Gin, X 5 is Gly or Gin, X 6 is Leu or Tyr, X 7 is Ser or His, and/or X 8 is Ser or Ala.

3 . The mutant according to claim 2 , wherein the amino acid fragment for the replacement is DDAQQTEA or SGPHGLSS.

4 . The mutant according to claim 3 , wherein the amino acid sequence of the mutant is set forth in SEQ ID NO: 4 or SEQ ID NO: 6.

5 . The mutant according to claim 1 , wherein the amino acid sequence of wild type human FG-F21 protein is set forth in SEQ ID NO: 1 or is an amino acid sequence having 90% or more, 95% or more, preferably 98% or more, more preferably 99% or more identity to SEQ Id NO: 1.

6 . A nucleic acid, encoding the mutant of any one of claims 1 - 5 .

7 . A vector, comprising the nucleic acid of claim 6 , wherein the vector is preferably an expression vector, more preferably a prokaryotic expression vector.

8 . A host cell, comprising the vector of claim 7 .

9 . A pharmaceutical composition, comprising the mutant of any one of claims 1 to 5 and a pharmaceutically acceptable carrier.

10 . Use of the mutant according to any one of claims 1 to 5 , the nucleic acid of claim 6 , the vector of claim 7 or the host cell of claim 8 in the manufacture of a medicament for the treatment of type 2 diabetes, obesity, dyslipidemia, or metabolic syndrome.

Assignees

• Hefei Inst Physical Sci Cas

Inventors

• Wang Junfeng
• Zhao Hongxin
• Zhu Lei

Classifications

• A61K38/1825

  Fibroblast growth factor [FGF] · CPC title

• C07K14/50 Primary

  Fibroblast growth factor [FGF] · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title