To provide EPO (erythropoietin) analogs that have a significantly longer half-life and enhanced erythropoietic activity in vivo but have no increased immunogenic properties.
The fusion protein having a prolonged half-life in vivo in comparison to naturally occurring or recombinant native human erythropoietin includes: (a) a naturally occurring human erythropoietin molecule having a cysteine residue proximate the C terminal thereof; and (b) an Fc fragment of human IgG including a hinge region wherein the N terminal of the Fc fragment is directly linked to the C terminal of the erythropoietin molecule, the Fc fragment is the same as a naturally occurring Fc fragment except that a cysteine residue located nearest the erythropoietin molecule has mutation substituted by a non-cysteine residue, the first cysteine in the hinge region is spaced at least 17 amino acids apart from the cysteine residue of the erythropoietin molecule.
DU YONG
ZHANG RUI
XU JING
LIU LONGBIN
JP2003530874A | 2003-10-21 | |||
JP2003508023A | 2003-03-04 |
WO2004004798A2 | 2004-01-15 | |||
WO2005001025A2 | 2005-01-06 |
Makoto Onda
Atsushi Honda