title: Effect of constant and variable domain glycosylation on pharmacokinetics of therapeutic antibodies in mice.
abstract: Previous studies on the effect of glycosylation on the elimination rate of antibodies have produced conflicting results. Here, we performed pharmacokinetic studies in mice with two preparations of a monoclonal IgG1 antibody enriched for complex type or high mannose type oligosaccharides at the Fc glycosylation site. No significant difference in the serum half-life was found between the two antibody glycoforms, nor was any difference observed in the serum half-lives of different complex type glycoforms. To evaluate the influence of glycosylation within the variable domain, a second monoclonal antibody, glycosylated in both the Fc and Fv domains, was separated into fractions containing different amounts of Fv-associated sialic acid and administered to mice. Again, no significant difference was found in the clearance rates of variants carrying different amounts of Fv-associated sialic acid or lacking Fv-glycosylation. These results suggest that glycosylation has little or no impact on the pharmacokinetic behavior of these two monoclonal antibodies in mice.
authors: Novartis Pharma AG, Biotechnology Development, Analytical Research and Development, 4002 Basel, Switzerland.
authors: Thomas A
authors: TA
authors: Millward
authors: Markus
authors: M
authors: Heitzmann
authors: Kurt
authors: K
authors: Bill
authors: Ulrich
authors: U
authors: Längle
authors: Peter
authors: P
authors: Schumacher
authors: Kurt
authors: K
authors: Forrer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism* / Q000494:pharmacology; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G