FGF21 variants

Patent metadata

Field	Value
Publication number	US-11230582-B2
Application number	US-201615776726-A
Country	US
Kind code	B2
Filing date	Dec 2, 2016
Priority date	Dec 2, 2015
Publication date	Jan 25, 2022
Grant date	Jan 25, 2022

Abstract

The present invention relates to polypeptide variants of human fibroblast growth factor 21 (FGF21) and fusion molecules thereof, as well as to nucleic acid molecules encoding the same. It further relates to their use as medicaments, in particular for the treatment of obesity, overweight, metabolic syndrome, diabetes mellitus, hyperglycemia, dyslipidemia, non-alcoholic steatohepatitis (NASH) and/or atherosclerosis.

First claim

The invention claimed is:

1. A variant of human fibroblast growth factor 21 (FGF21) comprising or consisting of the amino acid sequence of SEQ ID NO: 46 or 215.

2. The variant of human FGF21 according to claim 1 , fused or conjugated to a half-life extension module, wherein the half-life extension module is selected from the group consisting of a polymer, an unstructured (poly-)peptide chain, an elastin-like polypeptide (ELP), a serum protein, a serum protein binding molecule, an antibody, an immunoglobulin, an Fc region/domain of an immunoglobulin, and an immunoglobulin binding domain.

3. A fusion molecule comprising the variant of human FGF21 according to claim 1 and at least one other active pharmaceutical ingredient.

4. The fusion molecule according to claim 3 , wherein the at least one other active pharmaceutical ingredient is selected from the group consisting of insulin and insulin derivatives, GLP-1, GLP-1 analogues and GLP-1 receptor agonists, polymer bound GLP-1 and GLP-1 analogues, dual GLP-1/GIP agonists, dual GLP-1/glucagon receptor agonists, PYY3-36 or analogues thereof, pancreatic polypeptide or analogues thereof, glucagon receptor agonists or antagonists, GIP receptor agonists or antagonists, DDP-IV inhibitors, SGLT-2 inhibitors, and dual SGLT-2/SGLT-1 inhibitors.

5. A pharmaceutical composition comprising the variant of human FGF21 according to claim 1 and a pharmaceutically acceptable carrier and/or excipient.

6. A variant of human fibroblast growth factor 21 (FGF21), consisting of an amino acid sequence of SEQ ID NO: 215.

Assignees

• Sanofi Sa

Inventors

• Sommerfeld Mark
• Langer Thomas
• Boscheinen Oliver
• Dreyer Matthias
• Dittrich Werner
• Habermann Paul

Classifications

• 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

• C07K2319/20

  containing a tag with affinity for a non-protein ligand · CPC title

• C07K14/78

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title