Chapter 9 – Biobetter Biologics

Technological advances in the discovery and development of biologics have led to significant product and process improvement, affording drugs that are better for the patient. Biobetters are a new class of biopharmaceutical molecules developed by changes in the molecular profile through chemical, molecular, or functional changes. These changes allow the modified biologic to have considerable enhancements that include, but are not limited to, increased half-life, reduced toxicity, reduced immunogenicity, and enhanced pharmacodynamic effects. Development strategies for the optimization and development of biobetters fall into two major categories: (1) formulation approaches, and (2) protein engineering. This review focuses on the most common approaches to modifying biopharmaceuticals such as PEGylation, recombinant fusions, antibody–drug conjugates, affinity maturation, and antibody engineering and will touch only briefly on formulation approaches.