provided is a fusion protein comprising , at its carboxy terminal of human erythropoietin , a mutant having one to four amino acid substitutions in the carboxy terminal peptide fragment of a human chorionic gonadotropin β subunit , for increasing an in vivo half - life activity of epo . the in vivo half - life can be greatly elongated while retaining the intrinsic activity of the epo , without increasing the sugar chain content .