US 2024/0391971 A1 · GDF15 FUSION PROTEINS AND USES THEREOF

Abstract

A fusion protein comprises an Fc variant and a GDF15 active domain, wherein the Fc variant has amino acid substitutions at position 356 and/or position 439 of the IgG Fc according to EU numbering and still has the ability to form homodimer. By fusing the Fc variant with the GDF15 active domain, the Fc-GDF15 fusion protein has significantly improved physicochemical properties and recombinant expression levels, has in vitro activity equivalent to or better than natural GDF15 molecules, and has significantly prolonged in vivo circulating half-life, which can support the dosing frequency of once every two weeks or even once a month.

Claims24

Dependent claims

A GDF15 fusion protein comprising an immunoglobulin Fc variant, a peptide linker and a GDF15 active domain, wherein the Fc variant comprises amino acid substitutions at position 356 and/or position 439 of the IgG Fc according to EU numbering;

the GDF15 active domain is a full-length mature GDF15 protein, a N-terminal truncated GDF15 protein, or any variant that retains the biological activity of GDF15;
the peptide linker is selected from rigid peptide linker or rigid/flexible hybrid peptide linker;
and
the C-terminal of the Fc variant is linked via a peptide linker to the N-terminal of the GDF15 active domain.

1 more element

Dependencies are inferred from the claim text.

Gdf15 fusion proteins and uses thereof

Life of this patent

Gdf15 fusion proteins and uses thereof

Life of this patent

Abstract

Claims24