Protein pharmaceuticals: Discovery and preclinical development

Abstract

Proteins are natural molecules that carry out important cellular functions within our bodies. Their preciserole is crucialto the maintenance of good health. Malfunctioning proteins or those not produced optimally result in disease. The foundation of biopharmaceutical drug therapyhas therefore been to modulare cellular function by targeting specific proteins expressed on or outside the cell. Because most biopharmaceuticals are natural in origin, they are biologically and chemically very different from conventional medicines. In addition to differences in mechanism of action, biopharmaceuticals differ in theprocess by which they get manufactured and delivered. Because of their large, complex structure, they must often be produced by culturing cells and then purified froma host of cellular components. This can be time-consuming and costly. Also, most biopharmaceuticals are given by injection under the skinor by infusion into the veins. This creates significant limitations to their utility. Nonetheless, biopharmaceuticals can be very powerfuland sdective in disease applications such as in rheumatoid arthritis or cancer. This chapter describes methods by which proteins drugs are discovered, optimized and developed, It also covers novel agents and next generation proteins as well as some of the challenges and opportunities in the area. © 2009 Landes Bioscience and Springer Sciences-Business Media.