Disclosed is a fusion protein having a prolonged half-life in vivo in comparison to naturally occurring or recombinant native human erythropoietin comprising: (a) a naturally occurring human erythropoietin molecule having a cysteine residue proximate to a C terminal thereof and (b) a human IgG Fc fragment comprising a hinge region, wherein the N terminal of said Fc fragment is linked to said C terminal of said erythropoietin molecule and wherein said Fc fragment is naturally occurring except for a mutation replacing a cysteine residue of said hinge region located nearest said erythropoietin molecule with a non-cysteine residue, whereby the first cysteine residue of said hinge region located nearest said N terminal is spaced at least 17 amino acids apart from said cysteine residue of said erythropoietin molecule.
