Fusion proteins having mutated immunoglobulin hinge region

A fusion protein comprising from N-terminus to C-terminus:

• a non-immunoglobulin polypeptide selected from the group consisting of human erythropoietin (EPO) and human granulocyte-macrophage colony stimulating factor (GM-CSF);
• and
• an immunoglobulin component comprising a human IgG1 Fc fragment having a mutated IgG1 hinge region wherein the non-immunoglobulin polypeptide is directly coupled to the immunoglobulin component without an external linker peptide, wherein said IgG1 Fc fragment comprises said mutated IgG1 hinge region and IgG1 CH2 and CH3 domains,
• wherein the amino acid sequence of said mutated IgG1 hinge region is set forth in VEPKSGDKTSTCPPCP (SEQ ID NO:
• 24) or the amino acid sequence of SEQ ID NO:24, wherein one or more amino acid residues N-terminal to the glycine residue is deleted in SEQ ID NO:24;
• and
• wherein the fusion protein has enhanced biological activity in vivo in comparison to the native non-immunoglobulin polypeptide and in comparison to a fusion protein comprising the native non-immunoglobulin polypeptide and a human IgG1 Fc fragment comprising a native IgG1 hinge region and IgG1 CH2 and CH3 domains.

A fusion protein comprising from N-terminus to C-terminus:

• (i) a non-immunoglobulin polypeptide selected from the group consisting of human erythropoietin (EPO) and human granulocyte-macrophage colony stimulating factor (GM-CSF) and (ii) a human immunoglobulin component comprising an IgG1 Fc fragment, wherein the fusion protein has a prolonged half-life in vivo in comparison to naturally occurring or recombinant native non-immunoglobulin polypeptide, and wherein the non-immunoglobulin polypeptide is directly coupled to the immunoglobulin component without an external linker peptide,
• wherein said IgG1 Fc fragment comprises a mutated IgG1 hinge region and IgG1 CH2 and CH3 domains,
• wherein the amino acid sequence of said mutated IgG1 hinge region is set forth in VEPKSGDKTSTCPPCP (SEQ ID NO:
• 24) or the amino acid sequence of SEQ ID NO:24, wherein one or more amino acid residues N-terminal to the glycine residue is deleted in SEQ ID NO:24;
• and
• wherein the fusion protein has enhanced biological activity in vivo in comparison to the native non-immunoglobulin polypeptide and in comparison to a fusion protein comprising the native non-immunoglobulin polypeptide and a human IgG1 Fc fragment comprising a native IgG1 hinge region and IgG1 CH2 and CH3 domains.