Effect of constant and variable domain glycosylation on pharmacokinetics of therapeutic antibodies in mice

Biologicals. 2008 Jan;36(1):41-7. doi: 10.1016/j.biologicals.2007.05.003. Epub 2007 Sep 24.

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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / metabolism*
  • Antibodies, Monoclonal / pharmacology
  • Glycosylation
  • Humans
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / metabolism*
  • Immunoglobulin G / pharmacology
  • Mice

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin G