Protein heterogeneity and the immunogenicity of biotherapeutics

Nigh resolution analytical techniques reveal structural micro-heterogeneity within endogenous proteins, however,they are seen'as self' molecules by the immune system and immunological tolerance is established. In contrast the protein biotherapeutics are produced in non-human cells and multiple downstream protocols are employed in the isolation and purification of drug product; consequent micro-heterogeneities may beibeen'as'non-self' and potentially inimunogenic. In addition, extensive polymorphisms within. and between outbred human populations suggests that any given protein biotherapeutic may be allogenic, and potentiallyImmunogenic, when administered across different population groups. Further heterogeneity may result from differential intro-cellular process rig and the addition of co-, trans-, and post-translational modifications. These processes are explored against reported incidences of munogenicity for recombinant forms of human erythropoietin (EPO) and Immunaglobulin G (IgG)