By Karen Pihl-Carey

CuraGen Corp. completed the first protein interaction map of an entire genome, bringing the genomics-based drug discovery and development company one step closer to finding more effective therapeutics for cancer and other diseases.

The news sent the company's stock (NASDAQ:CRGN) skyrocketing 24 percent to close Thursday at $163.562, up $31.562. The stock was trading at $16.75 three months ago.

In a paper published in Thursday's issue of Nature, the company explained its process of identifying and mapping protein interaction of a complete genome, that of the yeast organism. The paper, titled "A Comprehensive Analysis of Protein-Protein Interactions in Saccharomyces cerevisiae," was featured on the cover of the journal.

"It is a clear commercial opportunity," said Jonathan Rothberg, founder, chairman and CEO of CuraGen. "In the paper, we discuss yeast genes that are involved in cell division. It's the bad cell division that leads to cancer. If you can stop the bad cell division, you can stop cancer. We also have breakthrough information on basic metabolism, and again, it was this [that is a factor] in cholesterol regulation."

The New Haven, Conn.-based company worked in collaboration with researcher Stanley Fields at the University of Washington to complete the map, an important milestone for CuraGen in its efforts to identify the protein interactions with other known genomes, such as the fruit fly (Drosophila melanogaster) and the human genome. The company expects it will take about two more years to identify the protein interactions for the human genome once the sequence is publicly available.

Rothberg said in a conference call that CuraGen's initial funding round was used to build a series of tools to understand the human genome and make drugs. The company's gene discovery technologies include SeqCalling, a sequence database product, and GeneCalling, which gives a quick expression analysis of almost all genes associated with diseases and drug responses.

"Our first major technology was to understand how each of us was different from each other - SNPs [single nucleotide polymorphisms]," Rothberg said. "Our second technology was designed to find the [one] gene out of your 100,000 genes in the genome. Our third technology can understand the function of genes."

CuraGen used its high-throughput PathCalling technology to identify and understand proteins on a genome-wide scale. PathCalling identifies novel protein interactions within biochemical pathways, and associates them with disease-related genes. The technology has a low rate of false positives and is applicable across almost all species, the company said. While the sequence of the yeast genome has been known for several years, PathCalling helped explain the function of those genes and resulting proteins.

"Right now, we can use that with our partners," Rothberg said. "They pay us for access to the information, and they can pay us to make drugs. If they use it right now in clinical trials or preclinically, they pay us."

In 1997, the company entered into a five-year deal potentially worth $33.5 million with Biogen Inc., of Cambridge, Mass., which gave Biogen database access and a genomics-based research collaboration aimed at identifying therapeutic proteins and disease targets. That same year, CuraGen entered into a $55 million deal with Genentech Inc., of South San Francisco, which covered a range of disease programs.

Last month, Curagen entered into a transgenics science-based genomics research program with DNX Transgenic Sciences, of Cranbury, N.J., a subsidiary of Montreal-based Phoenix International Life Sciences. DNX is developing transgenic mice based upon gene constructs provided by CuraGen, which will use the mice to identify novel therapeutic protein drugs.

And in December, the company formed a five-year alliance with Abgenix Inc., of Fremont, Calif., to use genomics technologies to identify up to 120 fully human antibody drug candidates to fight cancer, autoimmune disorders and other illnesses. (See BioWorld Today, Dec. 10, 1999, p. 1.)

The company also has collaborations with COR Therapeutics Inc., of South San Francisco, and Hoffmann-La Roche Inc., of Nutley, N.J., among other companies.

But aside from providing CuraGen with revenues through collaborations, Rothberg said the completion of the genomics map gives the company the tools needed to discover its own therapeutic products.

"Right now, they [collaborators] are using our functional information right before they go into the clinical trials. So it has impact near-term," he said. "However, we will benefit in the next three, four, five, six years in a very systematic way from this information. We have a business model now, and we have one to participate in the future of medicine."

Rothberg said CuraGen will make the information available to world scientists on its web site.