Comprehensive Characterization of N-Glycosylation in Darbepoetin Alfa

摘要

EPO analogues are representative glycoprotein drugs composed of heterogeneous,multiple antennary N-glycans.NESP~R and Aranesp~R 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~R and Aranesp~R showed difference in the ratio of N-glycans containing N-acetyllactosamine and Oacetylated 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-gly-cans,greater than 75%.This study increases understanding of N-glycan profiles and structural information of darbepoetin alfa.