Considerations for Construct and Affinity Design Goals
Application of an integrated approach for inclusion of pharmacology principles in drug development is a foundational step for effective modality design and selection of antibody-based therapeutics. Clarity on patient-related variables, manufacturing considerations, underlying biology and pathophysiology, as well as integration of key translational variables can accelerate drug development processes, ultimately benefiting patients in need of such therapies. Establishing design goals with respect to antibody affinity is a necessary step for achieving this goal and should be incorporated into the development strategies from the earliest stages of the discovery process for biologic modalities. Evaluation of affinity design goals is a complex process contingent on many critical variables. Knowledge of the target antigen biology and its role in the pathogenesis of disease is of high importance in establishing affinity design goals. Selection of the adequate affinity for a functional biologic construct should allow achievement of the maximum therapeutic benefit at a dose associated with a manageable cost of goods. This chapter will further expand on the topics discussed previously (Development of antibody-based therapeutics: translational considerations, Springer, New York, 2012).
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