Conjugation site heterogeneity causes variable electrostatic properties in Fc conjugates.

ABSTRACT: Immunoconjugates, including antibody-drug conjugates and Fc-conjugates, represent a rapidly growing class of therapeutics undergoing clinical development. Despite their growing popularity, the high intrinsic heterogeneity of immunoconjugates often complicates the development process and limits their widespread application. In particular, immunoconjugate charge variants exhibit markedly different colloidal stabilities, solubilities, pharmacokinetics, and tissue distributions. Charge variants arise spontaneously due to degradation and, depending on the type of drug, linker, and conjugation site, through drug conjugation. Electrostatic changes in naked antibodies often result in poor performance characteristics, and therefore, charge alterations due to degradation are critical to control. Cha

SUBMITTER: Boylan NJ 

PROVIDER: S-EPMC3713463 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature