Millward Thomas A, Heitzmann Markus, Bill Kurt, Längle Ulrich, Schumacher Peter, Forrer Kurt
Novartis Pharma AG, Biotechnology Development, Analytical Research and Development, 4002 Basel, Switzerland.
Biologicals. 2008 Jan;36(1):41-7. doi: 10.1016/j.biologicals.2007.05.003. Epub 2007 Sep 24.
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.
先前关于糖基化对抗体消除速率影响的研究得出了相互矛盾的结果。在此，我们用两种在Fc糖基化位点富含复合型或高甘露糖型寡糖的单克隆IgG1抗体制剂对小鼠进行了药代动力学研究。两种抗体糖型之间未发现血清半衰期有显著差异，不同复合型糖型的血清半衰期也未观察到差异。为了评估可变区内糖基化的影响，将一种在Fc和Fv结构域均进行了糖基化的第二单克隆抗体分离成含有不同量Fv相关唾液酸的组分，并给予小鼠。同样，携带不同量Fv相关唾液酸或缺乏Fv糖基化的变体的清除率也未发现显著差异。这些结果表明，糖基化对这两种单克隆抗体在小鼠体内的药代动力学行为几乎没有影响。
