Chimeric fibroblast growth factor 23/fibroblast growth factor 19 proteins and methods of use

Patent metadata

Field	Value
Publication number	US-9550820-B2
Application number	US-201414185366-A
Country	US
Kind code	B2
Filing date	Feb 20, 2014
Priority date	Feb 22, 2013
Publication date	Jan 24, 2017
Grant date	Jan 24, 2017

Abstract

The present invention relates to an isolated chimeric protein. The isolated chimeric protein includes an N-terminus coupled to a C-terminus, where the N-terminus includes an N-terminal portion from a fibroblast growth factor (“FGF”) 23 molecule and the C-terminus includes a C-terminal portion from an FGF19 molecule. The present invention also relates to a pharmaceutical composition including an isolated chimeric protein and a pharmaceutically acceptable carrier. The isolated chimeric protein includes an N-terminus coupled to a C-terminus, where the N-terminus includes an N-terminal portion from a fibroblast growth factor (“FGF”) 23 molecule and the C-terminus includes a C-terminal portion from an FGF19 molecule, and a pharmaceutically-acceptable carrier. Yet another aspect of the present invention relates to a method for treating a subject suffering from a disorder. This method includes selecting a subject suffering from the disorder and administering to the subject a therapeutically effective amount of a chimeric protein according to the present invention.

First claim

What is claimed:

1. An isolated chimeric protein comprising:
an N-terminus coupled to a C-terminus, wherein the N-terminus comprises an N-terminal portion from an FGF23 molecule and the C-terminus comprises a C-terminal portion from an FGF19 molecule, wherein the isolated chimeric protein has the amino acid sequence of SEQ ID NO: 254.

2. A pharmaceutical composition comprising the chimeric protein according to claim 1 and a pharmaceutically-acceptable carrier.

3. The pharmaceutical composition according to claim 2 further comprising:
one or more agents selected from the group consisting of an anti-inflammatory agent, an antidiabetic agent, a triglyceride-lowering agent, a cholesterol-lowering agent, an antihypertensive agent, and combinations thereof.

4. The pharmaceutical composition according to claim 3 further comprising an organotropic targeting agent.

5. The pharmaceutical composition according to claim 4 , wherein the targeting agent is covalently linked to the chimeric protein via a linker that is cleaved under physiological conditions.

6. A method for decreasing blood glucose levels in a subject in need thereof, the method comprising:
administering to the subject the chimeric protein according to claim 1 .

7. The method according to claim 6 , wherein the subject has diabetes, obesity, or metabolic syndrome.

8. The method according to claim 6 , wherein the subject has type II diabetes or gestational diabetes.

9. The method according to claim 6 , wherein the subject has type I diabetes.

10. The method according to claim 6 , wherein the subject has obesity.

11. The method according to claim 6 , wherein the subject has metabolic syndrome.

12. The method according to claim 6 , wherein said administering is carried out parenterally, subcutaneously, intravenously, intramuscularly, intraperitoneally, by intranasal instillation, by implantation, by intracavitary or intravesical instillation, intraocularly, intraarterially, intralesionally, transdermally, or by application to mucous membranes.

13. The method according to claim 6 , wherein the chimeric protein is administered with a pharmaceutically-acceptable carrier.

14. The method according to claim 6 , wherein the subject is a mammal.

15. The method according to claim 6 , wherein the subject is a human.

16. The method according to claim 6 , wherein the chimeric protein is co-administered with one or more of an anti-inflammatory agent, an antidiabetic agent, a triglyceride-lowering agent, a cholesterol-lowering agent, or an antihypertensive agent.

Assignees

• Mohammadi Moosa
• Goetz Regina
• Univ New York

Inventors

• Mohammadi Moosa
• Goetz Regina

Classifications

• C07K14/50 Primary

  Fibroblast growth factor [FGF] · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• A61K38/1825

  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

• A61K45/06

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