Considerations in Establishing Affinity Design Goals for Development of Antibody-Based Therapeutics
Establishing design goals with respect to antibody affinity is a critical consideration that should be incorporated into development strategies from the earliest stages of the discovery process for antibody-based therapeutics. Selection of the adequate affinity for a functional antibody should allow achievement of the maximum therapeutic benefit at a dose associated with a manageable cost of goods and the intended route of administration. Application of theoretical pharmacokinetic (PK) and pharmacodynamic (PD) modeling with incorporation of relevant parameters with respect to antibody PK properties and biodistribution, antigen turnover rate, and antigen concentrations under physiological and pathological conditions can facilitate determination of the optimum affinity required. This chapter will review the critical considerations necessary for the design of optimum affinity goals for antibody-based therapeutics.
KeywordsDesign Goal Antigen Concentration Soluble Antigen Therapeutic Antibody Effect Compartment
- Moore GL, Chen H, Karki S, Lazar GA (2010) Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions. MAbs 2(2):181–189Google Scholar
- Roskos L, Klakamp SL, Liang M, Arends R, Green L (2007) Molecular engineering II: antibody affinity. In: Dubel S (ed) Handbook of therapeutic antibodes. Wiley, pp 149–169Google Scholar