Methods of treating non-alcoholic steatohepatitis using FGF21 mutants

Patent metadata

Field	Value
Publication number	US-11072640-B2
Application number	US-201815996232-A
Country	US
Kind code	B2
Filing date	Jun 1, 2018
Priority date	Jun 4, 2008
Publication date	Jul 27, 2021
Grant date	Jul 27, 2021

Abstract

The invention provides methods for treating non-alcoholic steatohepatitis (NASH) using FGF21 mutant polypeptides.

First claim

What is claimed is:

1. A method of treating non-alcoholic steatohepatitis (NASH) comprising administering to a human patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a polypeptide comprising the amino acid sequence of SEQ ID NO:4 comprising:
(a) a substitution of an arginine residue for the leucine residue at position 98;
(b) a substitution of a glycine residue for the proline residue at position 171; and
(c) a substitution of a glutamic acid residue for the alanine residue at position 180.

2. The method of claim 1 , wherein the polypeptide comprises 1 to 10 amino acid residues fused to the C-terminus of the polypeptide.

3. The method of claim 1 , wherein the polypeptide is covalently linked to one or more polymers.

4. The method of claim 3 , wherein the polypeptide is covalently linked to PEG.

5. The method of claim 1 , wherein the polypeptide is fused to a heterologous amino acid sequence.

6. The method of claim 5 , wherein the polypeptide is fused to the heterologous amino acid sequence via a linker.

7. The method of claim 6 , wherein the linker comprises GGGGGSGGGSGGGGS (SEQ ID NO: 23).

8. The method of claim 6 , wherein the linker comprises GGGGSGGGGSGGGGS (SEQ ID NO: 31).

9. The method of claim 8 , wherein the heterologous amino acid sequence is an IgG constant domain or fragment thereof.

10. The method of claim 9 , wherein the IgG constant domain comprises the amino acid sequence of SEQ ID NO:13.

11. The method of claim 6 , wherein the heterologous amino acid sequence is an IgG constant domain or fragment thereof.

12. The method of claim 11 , wherein the IgG constant domain comprises the amino acid sequence of SEQ ID NO:13.

Assignees

• Amgen Inc

Inventors

• Belouski Edward John
• Ellison Murielle Marie
• Hamburger Agnes Eva
• Hecht Randy Ira
• Li Yue-Sheng
• Michaels Mark Leo
• Sun Jeonghoon
• Xu Jing

Classifications

• A61K2039/505

  comprising antibodies · 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

• C07K14/50 Primary

  Fibroblast growth factor [FGF] · CPC title

• C12N5/10

  Cells modified by introduction of foreign genetic material · CPC title

• C07K16/18

  against material from animals or humans · CPC title