Resolving Self-association of a Therapeutic Antibody by Formulation Optimization and Molecular Approaches

Casaz P, et al., 6(6):1533-9, Mabs, 2014

This article describes plausible approaches to resolve self-association of therapeutic antibodies. In particular, it demonstrates how formulation optimization and molecular approaches such as framework change, targeted mutagenesis, and isotype switch can benefit during the development of high concentration monoclonal-antibody formulations. The C4 human-antibody used in this investigation has the ability to neutralize diphtheria toxin and shows a strong potential to become a therapeutic antibody. When formulated at >30 mg/mL, C4 forms a white semi-solid gel at low temperatures. The affinities between C4 or C4-derivatives (generated by aforementioned approaches) and the antigen were measured using the BLI technology. An Octet system equipped with anti-human IgG biosensors was used in the capturing of C4 and its derivatives.

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