Engineering Therapeutic Antibodies for Development

Most chapters in this book describe methods to select antibodies and to engineer their properties for desired profiles in in-vitro assays or animal studies, focusing on binding and engaging the target. To become drugs, such early antibodies require further sequence optimization to ensure that the molecules can consistently be produced in high quantities fulfilling the necessary quality requirements and that they can be applied in humans with minimal unwanted side effects. In this chapter, we will discuss the nature of some side effects caused by monoclonal antibodies (mAbs) and how protein engineering methodologies are applied to reduce unwanted side effects. In addition, we will cover the challenges of manufacturing and process development with a focus on product homogeneity and explain how sequence optimization and process controls are applied to minimize product heterogeneity and ensure batch-to-batch consistency.