Engineering Monoclonal Antibodies to Enhance Drugability: A Case Study

n important consideration during the engineering process of an antibody is both the inherent conformational stability of the antibody as well as long-term stability. Understanding these parameters and what trends they follow will be critical throughout the biotherapeutic development. Differential Scanning Calorimetry (DSC) is a potent tool in probing these qualities. As a stability indicating assay, DSC provides insights for the selection of protein construct candidates. In the case of multidomain proteins, DSC uniquely allows the investigation of individual domains from multi-domain proteins like antibodies and Fc-conjugated proteins. In this application note, we compare DSC data with SEC-HPLC data from accelerated stability studies. For the engineered antibodies studied, there is a correlation between decreased thermostabilty based on DSC data, and greater aggregation formation during accelerated stability studies. This study demonstrates how DSC can be a useful tool in stability screening of engineered proteins.