Calgene Inc. said Wednesday that it has received a broadpatent on the use of antisense technology to regulate geneexpression in plant cells. But as with many biotech patents, itsissuance may be the beginning rather than the end of the story.

Antisense technology is the use of a reverse sequence of aspecific gene to repress the expression of that gene. U.S. patentNo. 5,107,065, issued on Tuesday, covers any plant gene in anyplant species. The patent does not cover non-plant genes.

Calgene shares (NASDAQ:CGNE) rose 63 cents to $11.50. TheDavis, Calif., company said it intends to develop alliances toexploit the technology outside of its core focus on tomatoes,canola and cotton.

However, potential patent conflicts loom with two othercompanies: ICI plc and Enzo Biochem Inc. (AMEX:ENZ).

Last October, the State University of New York and its exclusivelicensee, Enzo, won an antisense patent interference with theMassachusetts Institute of Technology. SUNY's patent claimshaven't issued, but Enzo has said that it expects that anycompanies doing genetic antisense work will have to obtain alicense from Enzo.

Calgene hasn't had formal discussions with Enzo, said LloydKunimoto, Calgene's vice president of corporate development."We've had one phone conversation with an Enzorepresentative to make sure we were aware of the existence oftheir patent application," he said.

"Enzo's European patent application doesn't seem to have anyclaims that would dominate the use of our patent," Kunimotosaid. "But we don't know what's pending in the U.S."

Enzo's European claims, published in 1985, are extremelybroad, covering any organism. "While no specific mention ofplants is made, the claims if issued would cover any organismor cellular material into which an antisense gene is inserted,"said Carol Talkington Verser, a technical specialist at theSheridan Ross & McIntosh law firm in Denver and a BioWorldcontributing editor. "But presumably the Patent Office wasaware of the Enzo patent when it issued the Calgene patent."

"It's an imponderable to say what will issue and what will beupheld by the courts," said Al Halluin of Fleiser, Dubb, Meyer &Lovejoy in San Francisco. "It's possible the PTO could limitEnzo's claims to the area they enabled: antisense done inunicellular organisms, which is mentioned in specific claims."

Enzo shares closed at $4.13, up 13 cents, on Wednesday.

The other potential conflict is with ICI, which is developingtomatoes and other crops using a variety of techniques,including antisense.

"We don't believe that our development plans infringe on theCalgene patent because we have a range of options," said SimonBest, business manager for fruit and vegetable technology."That's not to say there might not be some overlapping areas."

ICI is conducting field tests of transgenic fresh and canningtomatoes in Florida and California. The polygalacturonase genein those tomatoes has been down-regulated using both senseand antisense constructs, Best said. The PG enzyme causespectin degradation, which results in fruit softening due to cellwall breakdown.

Calgene uses antisense to target the same gene. Calgene's initialproduct, a tomato engineered for longer shelf life, is beingreviewed by the FDA, and the company anticipates marketingthe product in 1993.

Calgene also announced that it has licensed the ACC synthasegene for use in tomatoes from the U.S. Department ofAgriculture. DNA Plant Technology Corp. in March said that ithas licensed the technology for use in a genetically engineeredtomato it is developing.

-- Karen Bernstein BioWorld Staff

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