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Stability optimization of engineered mAbs

During biologics development, it is critical to ensure stability of a monoclonal antibody (mAb) with the ultimate goal of reaching the clinic. Biologics discovery often 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.

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Use of self-interaction parameters derived from light scattering experiments for better developability assessment of biologic therapeutics
Use of self-interaction parameters derived from light scattering experiments for better developability assessment of biologic therapeutics

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MST untangles the intricacy of a multimeric protein complex in its native form
MST untangles the intricacy of a multimeric protein complex in its native form

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