Protein pharmaceuticals: discovery and preclinical development.
Proteins are natural molecules that carry out important cellular functions within our bodies. Their precise role is crucial to the maintenance of good health. Malfunctioning proteins or those not produced optimally result in disease. The foundation of biopharmaceutical drug therapy has therefore been to modulate 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 the process by which they get manufactured and delivered. Because of their large, complex structure, they must often be produced by culturing cells and then purified from a host of cellular components. This can be time-consuming and costly. Also, most biopharmaceuticals are given by injection under the skin or by infusion into the veins. This creates significant limitations to their utility. Nonetheless, biopharmaceuticals can be very powerful and selective 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.
Gill
Davinder S
DS
Wyeth Research, Biological Technologies, 87 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA. dgill@wyeth.com
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001688:Biological Products / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical / Q000379:methods / Q000639:trends*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D007328:Insulin / Q000627:therapeutic use; D004364:Pharmaceutical Preparations; D014481:United States; D014486:United States Food and Drug Administration
D000911:Antibodies, Monoclonal; D001688:Biological Products; D007328:Insulin; D004364:Pharmaceutical Preparations