Fc fusion proteins of human EPO with increased biological activities relative
to rHuEPO on a molar basis are disclosed. The HuEPO-L-vFc fusion protein comprises
HuEPO, 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 HuEPO-L-vFc fusion proteins exhibit extended
serum half-life and increased biological activities, leading to improved pharmacokinetics
and pharmacodynamics, thus fewer injections will be needed within a period of time.
