title: N-glycosylation heterogeneity and the influence on structure, function and pharmacokinetics of monoclonal antibodies and Fc fusion proteins.
abstract: Monoclonal antibody and Fc fusion protein drugs are complex heterogeneous mixtures of numerous different protein variants and modifications. N-glycosylation as one of the most complex post-translational modification influences the structural characteristics of the antibodies Fc part thereby potentially modulating effector function and pharmacokinetics. Several investigations on the relationship between N-glycosylation and pharmacokinetics have been published. However, this structure-function relationship is not fully understood. In this review potential alterations with focus on N-glycosylation of mAbs and Fc fusion proteins and the possible effects on the pharmacokinetics are reviewed and the current understandings of the underlying mechanisms are described.
authors.affiliation: Sandoz Biopharmaceuticals, HEXAL AG, Oberhaching, Germany. Electronic address: fabian.higel@sandoz.com.
authors.forename: Fabian
authors.initials: F
authors.lastname: Higel
authors.affiliation: Sandoz Biopharmaceuticals, HEXAL AG, Oberhaching, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Seidl
authors.affiliation: IBMP - Institute for Biomedical and Pharmaceutical Research, Nuernberg-Heroldsberg, Germany; Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Sörgel
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig Maximilians-Universitaet Muenchen, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Friess
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000493:pharmacokinetics*; D006031:Glycosylation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry* / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D000911:Antibodies, Monoclonal; D007141:Immunoglobulin Fc Fragments; D011134:Polysaccharides
keywords: Fusion protein; Glyco-engineering; Monoclonal antibody; N-glycosylation; Pharmacokinetics