Comprehensive Characterization of N‐Glycosylation in Darbepoetin Alfa

Abstract

EPO analogues are representative glycoprotein drugs composed of heterogeneous, multiple antennary N‐glycans. NESP® and Aranesp® are hyperglycosylated EPO, marketed under the same international nonproprietary name as darbepoetin alfa. The multiple antennary N‐glycans are a key factor that increases the half‐life of the drug in the body, which is closely related to efficacy. Thus, control of N‐glycosylation is important in providing patients with consistent efficacy. This paper reports on the comprehensive characterization of N‐glycosylation of darbepoetin alfa products. The results of N‐glycan analysis of NESP® and Aranesp® showed difference in the ratio of N‐glycans containing N‐acetyllactosamine and O‐acetylated sialic acid. Although there were some differences, the overall N‐glycan structures and profiles were comparable. In particular, darbepoetin alfa products accounted for the largest proportion of tetra‐sialo N‐glycans, greater than 75%. This study increases understanding of N‐glycan profiles and structural information of darbepoetin alfa.