Engineered FGF compositions and methods of use thereof

Patent metadata

Field	Value
Publication number	US-10385113-B2
Application number	US-201715474268-A
Country	US
Kind code	B2
Filing date	Mar 30, 2017
Priority date	Mar 30, 2016
Publication date	Aug 20, 2019
Grant date	Aug 20, 2019

Abstract

The present invention relates to the development of stable mutants of FGF-1 and FGF-2. In particular, it relates to novel engineered FGF-1 and FGF-2 polypeptides as well as polynucleotides, DNA constructs, and vectors encoding such polypeptides. In another aspect, pharmaceutical compositions and hydrogels including the disclosed polypeptides, polynucleotides, DNA constructs, and vectors are provided. In a still further aspect, methods of treating conditions using the compositions disclosed herein are provided.

First claim

We claim:

1. A FGF polypeptide comprising a polypeptide selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 10, SEQ ID NO: 12, and a polypeptide having 80% sequence identity to SEQ ID NOs: 4, 6, 10 or 12 and comprising amino acid residue of 122 of SEQ ID NO: 4 or SEQ ID NO: 6 or amino acid residue 138 of SEQ ID NO: 10 or SEQ ID NO: 12.

2. The FGF polypeptide of claim 1 , wherein the FGF polypeptide comprises SEQ ID NO: 4 or a polypeptide having 80% sequence identity to SEQ ID NO: 4 and comprising amino acid residue of 122 of SEQ ID NO: 4.

3. The FGF polypeptide of claim 2 , wherein the FGF polypeptide comprises SEQ ID NO: 4.

4. A fusion protein comprising the FGF polypeptide of claim 1 and a membrane permeable peptide.

5. A pharmaceutical composition comprising the FGF polypeptide of claim 1 and a pharmaceutical carrier.

6. A hydrogel comprising the FGF polypeptide of claim 1 .

7. A method of treating a wound comprising administering the FGF polypeptide of claim 1 to a subject in an amount effective to heal the wound.

8. The method of claim 7 , wherein the subject is a human.

9. The FGF polypeptide of claim 1 , wherein the FGF polypeptide comprises SEQ ID NO: 6 or a polypeptide having 80% sequence identity to SEQ ID NO: 6 and comprising amino acid residue of 122 of SEQ ID NO: 6.

10. The FGF polypeptide of claim 9 , wherein the FGF polypeptide comprises SEQ ID NO: 6.

11. A pharmaceutical composition comprising the FGF polypeptide of claim 9 and a pharmaceutical carrier.

12. A hydrogel comprising the FGF polypeptide of claim 9 .

13. The FGF polypeptide of claim 1 , wherein the FGF polypeptide comprises SEQ ID NO: 10 or a polypeptide having 80% sequence identity to SEQ ID NO: 10 and comprising amino acid residue of 138 of SEQ ID NO: 10.

14. The FGF polypeptide of claim 13 , wherein the FGF polypeptide comprises SEQ ID NO: 10.

15. A pharmaceutical composition comprising the FGF polypeptide of claim 13 and a pharmaceutical carrier.

16. A hydrogel comprising the FGF polypeptide of claim 13 .

17. The FGF polypeptide of claim 1 , wherein the FGF polypeptide comprises SEQ ID NO: 12 or a polypeptide having 80% sequence identity to SEQ ID NO: 12 and comprising amino acid residue of 138 of SEQ ID NO: 12.

18. The FGF polypeptide of claim 17 , wherein the FGF polypeptide comprises SEQ ID NO: 12.

19. A pharmaceutical composition comprising the FGF polypeptide of claim 17 and a pharmaceutical carrier.

20. A hydrogel comprising the FGF polypeptide of claim 17 .

Assignees

• Univ Arkansas

Inventors

• Thallapuranam Suresh Kumar
• Zaharoff David A
• Jayanthi Srinivas
• Koppolu Bhanuprasanth
• Kerr Rebecca
• Balachandran Kartik
• Mcnabb David S

Classifications

• C07K14/71 Primary

  for growth factors; for growth regulators · CPC title

• A61K38/1825

  Fibroblast growth factor [FGF] · CPC title

• C07K14/50

  Fibroblast growth factor [FGF] · CPC title

• A61K38/16 Primary

  Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)} · CPC title

• A61K47/68

  the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment · CPC title