摘要 |
PROBLEM TO BE SOLVED: To provide erythropoietin conjugates having high in vivo bioactivity and excellent clinical effects. SOLUTION: The conjugates of erythropoietin (EPO) with poly(ethylene glycol) (PEG) comprise an erythropoietin glycoprotein having at least one free amino group and having the in vivo biological activity of causing bone marrow cells to increase production of reticulocytes and red blood cells and selected from the group consisting of human erythropoietin and analogs thereof which have sequence of human erythropoietin modified by the addition of from 1 to 6 glycosylation sites or a rearrangement of at least one glycosylation site; the conjugates exhibit increased half-life in circulating blood and residence time of plasma, reduced clearance and increased in vivo clinical activity as compared to unmodified EPO and conventional PEG-EPO conjugates. COPYRIGHT: (C)2004,JPO
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