Degradation of Polysorbate 20 by Sialate O-Acetylesterase in Monoclonal Antibody Formulations

Polysorbates (PS) are surfactants commonly added in biologics formulations that can protect proteins from denaturation and aggregation. However, decreases in polysorbate 20 (PS20) content have been observed in some monoclonal antibody formulations, causing the formation of visible and/or subvisible particles that ultimately compromise the quality and stability of the therapeutic protein products. It was determined that the particles are mainly composed of free fatty acid, suggesting enzymatic hydrolysis of PS is responsible for the degradation of PS. Enrichment of host cell proteins (HCPs) by immunoprecipitation followed by shotgun proteomics have been utilized to identify the HCPs that can hydrolyze PS20. One HCP, sialate O-acetylesterase (SIAE), demonstrated strong enzymatic activity for PS20 degradation even at low concentration (