Application Notes

APPLICATION NOTE Fahimeh Raoufi 1 , Marc Bailly 1 , Laurence Fayadat-Dilman 1 , Brett Thurlow 2 , Stefanie Kall 2 1 Merck & Co, Discovery Biologics, Protein Sciences, South San Francisco, CA USA 2 NanoTemper Technologies , Germany Abstract During biologics development, it is critical to ensure stability of a monoclonal antibody (mAb) with the ultimate goal of reaching the clinic. Biologics discovery o en involves huge libraries of candidates with varying biophysical characteristics, which need to be evaluated and optimized for greater developability and downstream success. Understanding how candidate sequence attributes alter biophysical parameters is necessary for improved rational design and delivery of biological candidates. Examining how specific mutations alter the biophysical profile of a mAb is an important first step in the candidate selection and developability workflow. Here, the Protein Sciences Department within Biologics Discovery at Merck used the Prometheus Panta and the parameters obtained from nano-differential scanning fluorimetry (nanoDSF), backreflection (turbidity), and dynamic light scattering (DLS) to characterize a selection of monoclonal antibodies with sequence diversity. Introduction Researchers involved in the discovery phase of therapeutic biologics, particularly monoclonal antibodies, require many parameters to assess the characteristics of their candidates to ensure their streamlined development and long-term success in the clinic. Early phase discovery involves vast libraries of candidates with sequence and epitope diversity. Establishing a better understanding of how mutations in the sequence of the antibodies change biophysical parameters of these diverse candidates helps drive sequence selection. Stability optimization of engineered mAbs

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