Fc fusion proteins of human growth hormone
Fc fusion proteins of human growth hormone with good biological activities relative to rhGH on a molar basis are disclosed. The hGH-L-vFc fusion protein comprises hGH, a flexible peptide linker of about 20 or fewer amino acids, and a human IgG Fc variant. The Fc variant is of a non-lytic nature and shows minimal undesirable Fc-mediated side effects. A method is also disclosed to make or produce such fusion proteins at high expression levels. Such hGH-L-vFc fusion proteins exhibit extended or prolonged serum half-life and/or good biological activities relative to that of rhGH on a molar basis, leading to improved pharmacokinetics and pharmacodynamics, thus fewer injections will be needed within a period of time.
1. A recombinant hGH-L-vFc fusion protein comprising hGH, a peptide linker, and a human IgG Fc variant, wherein the peptide linker containing about 20 or fewer amino acids is present between hGH and the human IgG Fc variant and wherein the human IgG Fc variant comprises a hinge, a CH2 domain, a CH3 domain of human IgG2, and serine residue at a position corresponding to residue 331 of SEQ ID NO:18.
2. The recombinant hGH-L-vFc fusion protein of claim 1 which exhibits a plasma half-life that is at least 2 times as long as that of rhGH (recombinant human growth hormone) when administered in vivo.
3. The recombinant hGH-L-vFc fusion protein of claim 1 wherein the peptide linker comprises two or more amino acids selected from the group consisting of glycine, serine, alanine, and threonine.
4. The hGH-L-vFc fusion protein of claim 3 which exhibits a plasma half-life that is at least 2 times as long as that of rhGH when administered in vivo.