ABSTRACT
It can be argued that the term biopharmaceutical is more of a marketing term than a technical term and has been hijacked to include a variety of drugs which are not biological polymers1,2; for the purpose of the current discussion, the term biopharmaceutical includes materials such as peptides/proteins, oligonucleotides/polynucleotides or oligosaccharides/polysaccharides. Albumin was the rst approved protein therapeutic; other early approved therapeutics include plasma protein fraction, thrombin, and intravenous immunoglobulin (IVIG).3-5 More recently there have been a number of therapeutic protein and peptide products.6-9 Therapeutic preparations of carbohydrate such as dextran and hydroxyethyl starch are colloids used for plasma expanders.10-12 Antisense nucleotides and small, interfering RNA molecules (siRNA) are being developed as therapeutics.13-16 The reader is directed to excellent recent reviews by Walsh, which provide global coverage of various biological molecules.17-19
Therapeutic preparations (active pharmaceutical ingredients; nal drug products) of protein, carbohydrate, lipid, or nucleic acids, or combinations thereof are usually prepared either by purication from natural sources such as blood or derived from fermentation or cell culture. There are some examples of chemical synthesis in the preparation of lipid-derived therapeutics such as liposomes,20,21 nucleic acids,22,23 and in the synthesis of peptides.24,25 While it has been possible to achieve the “semisynthesis” of a protein by chemical ligation26 (see Chapter 4), the total chemical synthesis of a protein has been achieved only for pancreatic ribonuclease.27 Other proteins28-31 have been altered only in part.
