Therapeutic agents comprising fusions of growth hormone and elastic peptides

Patent metadata

Field	Value
Publication number	US-9328154-B2
Application number	US-201414254660-A
Country	US
Kind code	B2
Filing date	Apr 16, 2014
Priority date	Dec 20, 2005
Publication date	May 3, 2016
Grant date	May 3, 2016

Abstract

The present invention provides therapeutic agents and compositions comprising elastic peptides and therapeutic proteins. Such peptides exhibit a flexible, extended conformation. In some embodiments, the therapeutic protein is a GLP-1 receptor agonist (e.g., GLP-1, exendin), insulin, or Factor VII/VIIa, including functional analogs. The present invention further provides encoding polynucleotides, as well as methods of making and using the therapeutic agents. The therapeutic agents have improvements in relation to their use as therapeutics, including, inter alia, one or more of half-life, clearance and/or persistance in the body, solubility, and bioavailability.

First claim

What is claimed is:

1. A therapeutic agent comprising a recombinant fusion between an elastic polypeptide and a therapeutic peptide, the therapeutic agent being formulated with a pharmaceutically acceptable carrier or excipient suitable for parenteral administration, and the therapeutic agent having an extended circulatory half-life when compared to the therapeutic peptide alone, wherein:
the therapeutic peptide comprises growth hormone; and
the elastic polypeptide has a pattern of proline-containing beta-turns forming an extended, non-globular structure, with no tertiary structure.

2. The therapeutic agent of claim 1 , wherein the elastic polypeptide forms a spiral conformation.

3. The therapeutic agent of claim 1 , wherein the elastic polypeptide comprises repeat amino acid motifs.

4. The therapeutic agent of claim 1 , wherein the therapeutic agent is formulated for injection.

5. The therapeutic agent of claim 4 wherein the therapeutic agent is formulated for subcutaneous injection.

6. The therapeutic agent of claim 5 , wherein the therapeutic agent is formulated for injection from about once to about five times per month.

7. The therapeutic agent of claim 4 , wherein the therapeutic agent is formulated for intramuscular injection.

8. The therapeutic agent of claim 7 wherein the therapeutic agent is formulated for injection from about once to about five times per month.

9. The therapeutic agent of claim 1 , wherein the growth hormone optionally has from 1 to 3 amino acid modifications independently selected from an insertion, deletion, and/or substitution.

10. The therapeutic agent of claim 1 , wherein the growth hormone is flanked on each terminus by an elastin-like peptide.

11. A therapeutic agent comprising a recombinant fusion between an elastic polypeptide and a therapeutic peptide, the therapeutic agent being formulated with a pharmaceutically acceptable carrier or excipient suitable for parenteral administration, and the therapeutic agent having an extended circulatory half-life when compared to the therapeutic peptide alone, wherein:
the therapeutic peptide comprises growth hormone;
the elastic polypeptide has a pattern of proline-containing beta-turns forming an extended, non-globular structure, with no tertiary structure, and
the elastic polypeptide consists essentially of glycine and hydrophobic amino acids selected from alanine, valine, leucine, isoleucine, proline, phenylalanine, tryptophan, and methionine, and optionally serine, threonine, and glutamic acid.

12. The therapeutic agent of claim 11 , wherein the elastic polypeptide contains amino acids selected from alanine, valine, glycine, serine, threonine, and glutamic acid.

13. The therapeutic agent of claim 11 , wherein the elastic polypeptide forms a spiral conformation.

14. The therapeutic agent of claim 11 , wherein the elastic polypeptide comprises repeat amino acid motifs.

15. The therapeutic agent of claim 11 wherein the therapeutic agent is formulated for injection.

16. The therapeutic agent of claim 15 , wherein the therapeutic agent is formulated for subcutaneous injection.

17. The therapeutic agent of claim 16 , wherein the therapeutic agent is formulated for injection from about once to about five times per month.

18. The therapeutic agent of claim 15 , wherein the therapeutic agent is formulated for intramuscular injection.

19. The therapeutic agent of claim 18 , wherein the therapeutic agent is formulated for injection from about once to about five times per month.

20. The therapeutic agent of claim 11 , wherein the growth hormone optionally has from 1 to 3 amino acid modifications independently selected from an insertion, deletion, and/or substitution.

21. The therapeutic agent of claim 11 , wherein the growth hormone is flanked on each terminus by an elastin-like peptide.

Assignees

• Univ Duke

Inventors

• Chilkoti Ashutosh

Classifications

• A61K47/64

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title

• C07K14/62

  Insulins · CPC title

• C07K14/52

  Cytokines; Lymphokines; Interferons · CPC title

• A61K47/6435

  the peptide or protein in the drug conjugate being a connective tissue peptide, e.g. collagen, fibronectin or gelatin · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title