Emerging methods for identifying monoclonal antibodies with low propensity to self-associate during the early discovery process.

Subcutaneous delivery of concentrated monoclonal antibodies (mAbs) is complicated by the propensity of mAbs to self-associate at elevated concentrations, which can lead to undesirable solution properties such as aggregation and abnormally high viscosity. Therefore, the selection of mAb candidates with low propensity to self-associate during early antibody discovery can significantly reduce challenges that may occur later during antibody development. However, it is difficult to use conventional biophysical methods for measuring weak mAb self-interactions during antibody discovery given the large number of antibody candidates as well as their low concentrations and purities. Nevertheless, significant progress has been made recently in adapting conventional biophysical methods as well as developing new ones for early identification of mAbs with low self-association propensities, which we highlight in this editorial. These advances should improve the selection of mAb candidates suitable for the extreme requirements of concentrated formulations necessary for subcutaneous delivery of therapeutic antibodies.