Proteins and antibodies were supposed to be the raison d'etre for biotechnology. But with the exception of the "low-hanging fruit" of previously known proteins like insulin, human growth hormone (hGH) and erythropoietin (EPO), and the recent increase in marketed antibodies, protein therapeutics have not been the slam dunk that some expected them to be.

Initially the small number of known proteins limited the probability that any one of them would have therapeutic value, and at the same time, the technology was lacking to discover and sift through new proteins in a systematic way.

But technological and scientific developments over the last decade have solved most of these impediments, both broadening the disease areas that can be tackled and dramatically increasing the chances of successfully bringing products to market. That success can be seen in the fact that by BioCentury's count, 34 of the 59 marketed proteins and antibodies were approved in the last five years (see "Approved Protein & Antibody Therapeutics", A6). Thus going forward, therapeutic proteins, including antibodies, are likely to become an even more established group in the drug armamentarium, complementing small molecules.

In particular, genomics has provided researchers with an enormously increased pool from which to select specific proteins for development, and the ability to humanize antibodies has made their therapeutic potential a reality. As a result, some observers see the industry as entering a golden age of protein therapeutics, with as many as 10,000 proteins likely to have therapeutic value either themselves or as targets for therapeutic antibodies.

Nevertheless, some roadblocks remain in place, such as systematically sifting through the thousands of proteins discovered through the human genome project to find those with therapeutic potential, and developing the delivery technologies necessary to put protein administration on an equal footing with small molecule drugs.

Obstacles overcome

In the early days of the industry, recombinant DNA technology held out the promise of therapeutics based on biology rather than chemistry. But dosing proved to be an issue as researchers moved from the use of already-known proteins to novel candidates.