The antibody function is affected when aspartate isomerization occurs in binding area such as CDRs. Isomerization could also lead to charge heterogeneity on the protein surface and therefore results in fragmentation due to cleavage on the peptide backbone. The fragmentation reaction mostly occurs below pH 5 and Asp-Pro peptide bonds are more susceptible than other peptide bonds. Immunogenicity is potentially increased by aspartate isomerization and fragmentation leads to protein aggregation.

As the Aspartate isomerization occurs during the manufacturing process, depending on the environment conditions, the process parameters should be carefully selected to minimize the risks. For antibody candidate selection, we recommend to avoid those with potential isomerization motifs in the antigen binding interfaces where possible.