Fibroblast growth factor-21-Fc fusion proteins

Patent metadata

Field	Value
Publication number	US-11944664-B2
Application number	US-202117410307-A
Country	US
Kind code	B2
Filing date	Aug 24, 2021
Priority date	Sep 26, 2011
Publication date	Apr 2, 2024
Grant date	Apr 2, 2024

Abstract

The invention relates to the identification of fusion proteins comprising polypeptide and protein variants of fibroblast growth factor 21 (FGF21) with improved pharmaceutical properties. Also disclosed are methods for treating FGF21-associated disorders, including metabolic conditions.

First claim

What is claimed is:

1. A fusion protein comprising a fibroblast growth factor 21 (FGF21) variant and an Fc region, wherein the FGF21 variant comprises an amino acid sequence with at least 95% identity to the full length hFGF21 sequence SEQ ID NO:1, and comprises at least the following mutations relative to SEQ ID NO:1: Q55C, G148C, K150R, P158S, S195A, P199G, and G202A, and one of R105K and A109T.

2. The fusion protein of claim 1 , wherein the FGF21 variant comprises a disulfide bond between Cys103 and Cys121, positions referring to the amino acid position of the full length hFGF21 sequence SEQ ID NO:1.

3. The fusion protein of claim 1 , wherein the FGF21 variant comprises an engineered disulfide bond GIn55Cys-Gly148Cys.

4. The fusion protein of claim 1 , wherein the Fc region is linked to the FGF21 variant via a linker.

5. The fusion protein of claim 4 , wherein the linker is 1 to 20 amino acids in length.

6. The fusion protein of claim 4 , wherein the linker comprises glycine and serine residues.

7. The fusion protein of claim 6 , wherein the FGF21 variant is linked to the Fc region by a GS linker.

8. The fusion protein of claim 1 , wherein the Fc region of the fusion protein is a modified Fc fragment.

9. The fusion protein of claim 8 , wherein the Fc region is a modified Fc fragment with a LALA mutation.

Assignees

• Novartis Ag

Inventors

• Boettcher Brian R
• Caplan Shari Lynn
• Daniels Douglas S
• Hamamatsu Norio
• Licht Stuart
• Weldon Stephen Craig

Classifications

• A61K38/1825 Primary

  Fibroblast growth factor [FGF] · CPC title

• A61K45/06

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

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title