Human IgG heavy chain genes usually encode a C-terminal lysine. However, this residue is mostly missing in the endogenous antibodies isolated from serum, while some low but variable level of C-terminal lysine is present on therapeutic antibodies expressed in mammalian cell culture systems. Whether the mass and charge heterogeneity caused by C-terminal Lysine processing affect antibody bioactivity or safety profile is still unknown.

The level of the Lysine processing varies as process condition changes and each species should be monitoredand kept within predefined limits. It is sufficient to carefully control the process parameters and conditions. Since C-terminal Lysines are naturally cleaved off and do not effect the potency or safety of the antibody candidate, they can be simply removed by protein engineering.