 This study examined the effect of changing the surface charge of a monoclonal antibody, MAB, to improve its pharmacokinetics, PK. The MAB was engineered using a combination of structure-based design and preclinical models to identify a humanized candidate with optimal PK properties. The initial humanized version had a faster clearance rate in non-human primate models, so it was modified again to reduce the clearance rate. This modification involved changing the isoelectric point, pi, from 7.5 to 6.5, which resulted in a decrease in surface charge and a slower clearance rate in both non-human primates and humanized mice. The result suggests that surface charge plays an important role in determining the PK of MABs, and that careful consideration should be given to the surface charge when selecting and screening humanized candidates. This article was authored by Roman Olia, Aline Fuchs, Florence Gauia, and others. We are article.tv, links in the description below.