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Human Genome Sciences, like many of these companies, hopes to use proteins themselves as drugs--and has six in clinical trials. CEO William Haseltine says HGS does hundreds of experiments on some 10,000 distinct proteins in its hunt for novel drugs. The firm has invested heavily in bioinformatics to get a grip on the mounds of data this process generates (see box).
That investment has paid off. HGS moved a drug against autoimmune disease into clinical trials within 18 months of its discovery. Haseltine has managed his pharmaceutical aspirations astutely, building commercial manufacturing facilities for proteins years in advance--aware that a lack of capacity has hampered some of the most exciting biotech drugs. "It is my belief that if a skill is critical to your success," says Haseltine, "you must build it and control it yourself." But underscoring the risks of drug discovery, HGS's shares dropped 10% last week when it announced that its leading drug in clinical trials is safe but seemingly ineffective.
Proteomics is all the rage in Europe as well. The British biotech Oxford GlycoSciences announced this month that it had filed for patents on 4,000 proteins. It has $280 million in cash reserves and is awaiting U.S. and European approval of a drug for Gaucher disease, a rare inherited disorder.
To speed the discovery of drugs that attack their targets without poisoning those who take them, many biotech firms rely on design rather than serendipity. Vertex Pharmaceuticals of Cambridge, Mass., has halved, to 18 months, the time it takes to discover candidate drugs and is today among the most prolific generators of leads.
Yet the nuts and bolts of its discovery strategy are not radically new. Vertex essentially finds the structures of its target proteins and designs molecules that slip selectively into the grooves found along the proteins' surfaces. It did this expertly in designing the anti-HIV drug Agenerase, which it promotes with GlaxoSmithKline. A handful of other firms have developed their own drugs in similar ways.
Because a protein's structure is essential to its function, those proteins that perform similar functions often have stretches where they are similarly shaped. Instead of focusing on the structure of just one target, Vertex homes in on entire families of proteins as it seeks out its leads. This is done by crystallizing a protein of interest and exposing it to intense X-ray beams. The way those beams are scattered reveals how atoms along the molecule's length are arranged--information that is converted into a protein structure by computers. Chemists use this structure to digitally model molecules that should fit--like the pieces of a jigsaw puzzle--into grooves on the protein's surface. When the company has found about 100 that might work, it produces them and tests each out against the target.