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Zeneca Licenses Rosetta s Technology for Genomics-Based Herbicide Development

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KIRKLAND, Wash.-- Rosetta Inpharmatics, a privately held bioinformatics company here with informatics tools, biological platforms, and proprietary global expression datasets, licensed its technology this month to Zeneca Agrochemicals. Zeneca will use Rosetta's Genome Reporter Matrix to select lead compounds for development of chemical herbicides and insecticides.

The technology, originally developed by Acacia Biosciences, a Richmond, Calif., company that Rosetta acquired in February, is designed to compare the expression profile of an unknown lead with a collection of standards that Rosetta has already applied. "It provides the unique ability to fingerprint the expression profiles of experimental compounds in relation to a library of standards," said David Evans, Zeneca Agrochemicals' director of research and development.

"This is an application of functional genomics to our chemical discovery business," said Martin Battersby, who manages a staff of some 250 people working at Zeneca's Jealotts Hill, UK, facility on gene discovery for crop enhancement and crop protection.

Battersby explained, "Rosetta's technology looks at the expression of all the genes of yeast, about 6,000 of them, and at how those genes go up and down in terms of expression when subjected to chemical treatment." The practice reveals which genes are affected by the chemical being tested, and genes that are upregulated, perhaps in response to the chemical. Said Battersby, "That gives you some early idea of the quality of the lead that you find."

For Rosetta, the acquisition of Acacia's Genome Reporter Matrix "fit very well into a series of programs already underway," said Mark Benjamin, Rosetta's senior director of business development. Rosetta's platform, he explained, includes "very strong biology, yeast development, and a unique microarray development program," which uses technology developed in the University of Washington laboratory of Leroy Hood, a Rosetta founder.

Hood founded the company in June 1997 with the director of the Fred Hutchinson Cancer Research Center, Leland Hartwell, and Stephen Friend, the center's head of molecular pharmacology. By September of that year, Rosetta had concluded a private financing round that brought in $17.5 million including significant investments from Olympic Venture Partners, Lombard Odier, Tredegar, and Vulcan Northwest.

Rosetta ready to partner

Now, Benjamin said, "With the acquisition of Acacia, Rosetta has gotten its technology to a position where it's really ready to partner." He added, "We anticipate much bigger deals in the next year."

Although Rosetta's website indicates that the company is focused exclusively on the pharmaceutical industry, Benjamin said one reason he was brought on board last month "is to change a lot of those outward perceptions." He said that while drug discovery will still be Rosetta's primary focus, the company plans to court the agrichemical discovery industry as well.

Benjamin contended that data interpretation, "something that is absolutely critical to the future of genomics," has not been handled well by most companies in the field. "Many are happy to provide the microarray and the database, but interpreting results is a whole other story." Rosetta's "enormous effort in bioinformatics" will tackle that deficit, he said.

"Everybody talks about genomics and this revolution, but all that's really happened is that tools have been developed. Now, using the tools is really a challenge," Benjamin said, adding, "You can buy a microarray relatively cheaply, but using it in a way that will help you design better drugs is a major challenge."

Benjamin said Rosetta is using bioinformatics to utilize genomics. "Rather than just provide a tool to someone, we're actually going to help them design drugs," he remarked.

More than just fungicides

Zeneca's Battersby told BioInform that, even though Rosetta's system is yeast-based, the technology will be useful for testing more than just fungicides. Weeds and insects can be screened against, too, he said. "Rosetta already demonstrated that they can apply this technology toward all sorts of potential modes of action, so I'm thinking of fungicides, insecticides, and herbicides," said Battersby.

He continued, "There are a number of biochemical processes that all organisms have that you can model in yeast. Clearly there are some you can't. Yeast doesn't have a nervous system, and therefore there are certain insecticidal effects you couldn't detect. But," he added, "you could expect to detect how a cell metabolizes the compound with this technology."

Battersby also explained the difference between applying the technology toward pharmaceutical development, which Rosetta expects to be its bigger market, versus agricultural chemical discovery. "The agricultural business is very different from the pharmaceutical business. What we operate is a high-throughput screening process to discover active starting points against whole organisms. So we will screen against whole weeds and whole insects and we'll do that in a high-throughput way," Battersby said.

For instance, he said, in 1998 his group tested 100,000 compounds. "When you do that you get lead compounds that control targets of interest to you, but you don't know how they work." That's why early information about mode of action and metabolism selectivity is so useful. "The earlier you can get that information, the better able you are to select the best leads," he said. "You're screening 100,000 chemicals, and you hope that you've got a lot of interesting things to follow up," Battersby said, adding, "This technology will help us make a choice between the more interesting ones and the ones that are perhaps less interesting."

--Adrienne Burke

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