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

Millward, Thomas A; Heitzmann, Markus; Bill, Kurt; Längle, Ulrich; Schumacher, Peter; Forrer, Kurt (2008). Effect of constant and variable domain glycosylation on pharmacokinetics of therapeutic antibodies in mice. Biologicals, 36(1), pp. 41-7. London: Elsevier 10.1016/j.biologicals.2007.05.003

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic and Policlinic for Anaesthesiology and Pain Therapy

UniBE Contributor:

Schumacher, Peter

ISSN:

1045-1056

ISBN:

17890101

Publisher:

Elsevier

Language:

English

Submitter:

Jeannie Wurz

Date Deposited:

04 Oct 2013 15:03

Last Modified:

23 Jan 2018 12:17

Publisher DOI:

10.1016/j.biologicals.2007.05.003

PubMed ID:

17890101

Web of Science ID:

000252987900006

URI:

https://boris.unibe.ch/id/eprint/27291 (FactScience: 105917)

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