Composite Protein™ technology uses EpiScreen™ technology to map helper CD4+ T cell epitopes within the sequence of the starting protein. T cell epitopes are then removed from the protein as follows;
- mutations are designed using iTope™ and TCED™ in silico technologies in order to reduce/eliminate binding to human MHC class II
- T cell receptor contact residues are targeted to disrupt recognition of peptide/MHC class II complexes
- T cell epitopes are modified to introduce germ-line sequences from related proteins (if available) with high abundance in vivo to which the human immune system is tolerant (e.g. germ-line antibody variable region sequences)
- structural and homology analysis will guide the targeting and substitution of key amino acids in order to maintain desired protein activity
- T cell epitopes are prioritized for removal based on potency, and a matrix of sequence variants are designed and tested for the removal of T cell epitopes, whilst avoiding loss of protein activity.