Cell culture media supplementation of bioflavonoids for the targeted reduction of acidic species charge variants on recombinant therapeutic proteins

Charge variants in recombinant proteins are an important series of protein modifications, whose potential role on protein stability, activity, immunogenicity, and pharmacokinetics continues to be studied. Monoclonal antibodies in particular have been shown to have a wide range of acidic species variants, including those associated with the addition of covalent modifications as well as the chemical degradation at specific peptide regions on the antibody. These variants play a significant role toward the overall heterogeneity of recombinant therapeutic proteins and are typically monitored during manufacturing to ensure they lie within proven acceptable ranges. In this work, it has been found that the supplementation of members of the bioflavonoid chemical family into mammalian cell culture media was effective toward the reduction of acidic species charge variants on recombinant monoclonal antibodies and dual variable domain immunoglobulins. The demonstrated reduction in acidic species through the use of bioflavonoids facilitates the manufacturing of a less heterogeneous product with potential improvements in antibody structure and function. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1039–1052, 2015