Monsanto gets deeper into genomics Monsanto is expanding its access to gene-sequencing technologies through alliances with two leading small geno mics companies—Millennium Pharma ceuticals of Cambridge, Mass., and Incyte Pharmaceuticals of Palo Alto, Calif. In an increasingly competitive life sci ences market—which includes pharma ceuticals, crop protection products, and seeds—Monsanto and others are trying to improve their understanding of the underlying genetics and gene functions of plants, microbes, and humans. Many new drug and agricultural products are based on biotechnology, and small genomics companies have developed an expertise in technologies that larger companies want now. "This new venture couples Millenni um's broad, integrated technology plat form with Monsanto's extensive research program in agriculture, food, and phar maceuticals to create a leading genomicsbased life sciences presence," says Hendrik A. Verfaillie, Monsanto's president. Monsanto will pay Millennium $118 mil lion over five years in licensing and technology transfer fees. Millennium could receive up to another $100 mil lion if certain research objectives are met. To facilitate the collaboration, Monsanto will create and fund a wholly owned, Cambridge-based subsidiary. The as yet unnamed subsidiary will em ploy 100 scientists, most likely hired from outside both firms, in 1998 and as many as 150 in the future. Monsanto has been collaborating with Incyte for a year on the sequencing of plant genes. Under the expanded collab oration, Incyte's genomics capabilities and databases are to be applied broadly and nonexclusively to other areas of Monsanto's life sciences businesses. Al though the multiyear partnership is the broadest and largest financial commit ment Incyte has secured to date, mone tary terms have not been made public. Both Incyte and Millennium have col laborations with other major companies and could receive royalties on products re sulting from their technology collabora tions with Monsanto. Incyte collaborates broadly across the life sciences, whereas the four-and-a-half-year-old Millennium has alliances primarily with pharmaceutical producers. Including Monsanto, Millenni um's alliances are worth a potential total of $700 million.
Companies involved in agricultural bio technology "don't want to reinvent the wheel," notes Sano M. Shimoda, president of BioScience Securities, Orinda, Calif., "so they develop strategic relationships with those companies that are at the leading edge." "It's a race," says Shimoda. "Everyone is sequencing genes for corn and a lot of other crops. But sequencing and finding the genes is one thing; understanding what the genes do is key. And that's where these companies are investing money to develop an information data base to analyze and understand what the function is of the genes that they are finding." Ann Thayer
Medication for cocaine, PCP addicts emerging Medications that could quickly calm a drug addict crazed by an overdose of phencyclidine (PCP) or banish the crav ing for cocaine that casts users of the drug into a tenacious cycle of addiction are on the horizon. At the annual meeting of the Society for Neuroscience, held late last month in New Orleans, scientists described an an tibody therapy that rapidly halts the fre netic behavior of rats overdosed with PCP. Another group reported a cocaine analog that reduces desire for the drug in animals. The antibody molecules that, like a magnet, snatch PCP compounds out of the brain and escort them out of the body were developed by S. Michael Owens, a professor of pharmacology and toxicology at the University of Arkansas for Medical Sciences, Little Rock. In designing them, Owens generated rabbit antibodies against different PCPlike molecules to determine the molecu lar features needed for binding to the PCP brain receptor. His research team then generated a monoclonal antibody in
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mice against the best of these haptens. After generating large quantities of the antibody, he enzymatically clipped the antibodies to produce smaller PCPbinding fragments. These fragments were injected into the bloodstreams of overdosed rats. "Within 10 minutes, the brain concen tration of PCP is reduced about 90%," said Owens. "It's a mass-action effect." Because the antibody fragment's affinity for PCP is about 80 times greater than that of PCP receptors, it disrupts the equilibrium of PCP in the brain and draws the drug across the blood-brain barrier into the bloodstream. Within 20 minutes, antibody-treated rats were completely calm and grooming themselves, while control rats were still in a tailspin. "It's a complete cure in our ani mal models," Owens said. The antibody fragment has elicited hardly any antigenic response in rats given very large doses, he noted. Owens is scaling up antibody produc tion using "trash cans full of tissue cul ture media. . . . I think we are one of the largest producers of monoclonal antibod ies in academia," he said. He believes the antibody approach can be adapted for other drugs of abuse and is set to begin studies with methamphetamine. Meanwhile, at Yerkes Primate Re search Center, Emory University, Atlanta, animals that self-administer cocaine are showing a reduced craving for the drug when injected with a cocaine analog called RTI-113, said Michael J. Kuhar, chief of the division of neuroscience. Kuhar has focused on using an analog to treat cocaine addiction the way meth adone treats heroin addiction or the nic otine patch helps cigarette smokers quit the habit. He selected RTI-113 from roughly 20 potential candidates chosen from a pool of "about 500 cocaine ana logs synthesized over 10 years" by collab orator F. Ivy Carroll, a chemist at Re search Triangle Institute, Research Trian gle Park, N.C. RTI-113 mimics cocaine in binding to dopamine transporter molecules. But it enters the brain more slowly and stays NOVEMBER 3, 1997 C&EN 9
