Use DSC to select antibody with lowest propensity to aggregate. An 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 stability 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 stable protein construct candidates. In the case of multi-domain proteins, DSC uniquely allows the investigation of the stability of individual domains from multi-domain proteins like antibodies and Fc-conjugated proteins. In this application note, we compare stability data predicted by DSC of different engineered antibodies with SEC-HPLC data from accelerated stability studies. For the engineered proteins 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.

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