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CuraGen Sees Comprehensive Bioinformatics Structure as Key to Drug Discovery Success


CuraGen''''s partnership with Bayer yielded its first fruits recently in the form of 12 novel drug targets linked to obesity and diabetes. The rapid pace of the discovery collaboration, which began in January, is largely due to CuraGen''''s informatics capabilities, said Jim Golden, director of bioinformatics at CuraGen.

"The bioinformatics was central" to the project''''s success, said Golden. "The integrated bioinformatics allowed us to put together a cohesive and integrated and iterative picture. We gave Bayer an integrated picture of a number of targets which allowed them to quickly decide which genes had the most promise as drug targets and elect to pursue those."

While CuraGen considers itself first and foremost a drug discovery company, a quick glance at the company''''s organizational chart reveals the importance it places on its bioinformatics capabilities. CuraGen has four directors of bioinformatics: Golden, along with Steven Gold, James Knight, and Martin Leach, share the responsibility of supporting what CEO Jonathan Rothberg has often called CuraGen''''s core competency.

Gold is responsible for the company''''s LIMS and workflow, Knight heads up database and visualization software development, and Leach designed the computational biology tools that make up part of the company''''s GeneScape platform.

Golden, who serves as a product manager for the bioinformatics group, credited Leach''''s handiwork with delivering the targets to Bayer so quickly. The drug development portion of GeneScape tracks the targets that are nominated and elected for follow-up, "so it gave Bayer a very high-level profile of all these targets from a bioinformatics standpoint with the ability to drill down to the sequence, the pathway, the SNP, etc.," Golden said.

CuraGen considers its approach to discovery unique. "What we call a target is different that what others may call a target," said Mark Vincent, director of corporate communications and investor relations at CuraGen. "An up-regulated gene is not a target to us. We provide our partners with a comprehensive picture of gene activity that we quantify a number of ways."

The GeneScape platform is central to the company''''s discovery and validation process. It serves as a LIMS system to monitor every step of each experiment performed in the lab, controlling workflow and instrumentation, tracking samples, and providing process control. It also integrates information from public and private databases, annotations, and available scientific literature, all of which are updated nightly. Finally, GeneScape serves as the portal through which CuraGen scientists as well as the company''''s collaborating partners can access a suite of discovery tools to manipulate, analyze, and visualize the entire body of data.

Information from a total of eight validation steps for each target is integrated into GeneScape, allowing CuraGen to "deliver targets that will make it to market," said Golden. This approach has not only been borne out by the company''''s collaborators, who include Bayer and Abgenix among others, but in CuraGen''''s own discovery efforts.

The company has recently built a chromosomal map of what it considers to be the "pharmaceutically tractable genome"ó8,200-8,400 known genes that CuraGen confidently says comprise the only portion of the genome relevant to those seeking druggable targets. CuraGen has placed 5,000 of these genes at a time on a chip for its discovery programs.

So far, CuraGen has 357 protein targets, 1,557 antibody targets, and 3,290 small-molecule targets under evaluation. Golden estimated that the company''''s integrated bioinformatics approach could reduce the 7-10 years required for a linear approach to target generation to 1-3 years.

Likewise, the company''''s bioinformatics group works under a compressed schedule, adopting the tenets of "extreme programming" to pair developers together who write code in a matter of days rather than weeks.

Golden said the bioinformatics group is growing along with the rest of the company. CuraGen recently purchased 88 acres of land near its Branford, Conn., facility, where it intends house its current operations, now split between New Haven and Branford. The company''''s total staff was 415 at last count, but the company is hiring so rapidly that the headcount is in constant flux. Golden expects the current bioinformatics staff of 60 to increase to 100 by year-end.

Golden said CuraGen has been approached by companies interested in licensing part of GeneScape and is "talking about whether that makes sense for us." He noted that CuraGen''''s recently launched spin-off 454 was formed with the purpose of commercializing some of CuraGen''''s technology without detracting from the company''''s push to get drugs to clinical trials.

For the moment, however, CuraGen is not seeking to derive additional revenue by licensing its bioinformatics tools. With $550 million in the bank and plenty of revenue from its current partnerships, the company is focusing squarely upon its goal to become a drug discovery company. "Our collaborative research partnerships give us near-term revenues that we could use to become profitable," said Vincent, "but our business plan is to develop drugs, so we''''re investing it back into drug development."

— BT


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