Second-generation biopharmaceuticals

The majority of first generation biopharmaceuticals are unengineered murine monoclonal antibodies or simple replacement proteins displaying an identical amino acid sequence to a native human protein. While some such products continue to be approved, an increasing number of modem biopharmaceuticals are engineered, second-generation products. Engineering can entail alteration of amino acid sequence, alteration of the glycocomponent of a glycosylated protein, or the covalent attachment of chemical moieties such as polyethylene glycol. Engineering has been applied in order to alter a protein's immunological or pharmacokinetic profile, or in order to generate novel fusion products. Better understanding of the links between protein structure and function will underpin the development of an increasing number of engineered biopharmaceuticals in the future. (C) 2004 Elsevier B.V. All rights reserved.