SAN FRANCISCO -- Closing arguments were expected to windup today in the patent infringement trial in U.S. District Courthere between Xoma Corp. and Centocor Inc. over competingantibodies to treat gram-negative sepsis.

Jurors are being asked to decide four issues: Has Centocorproved that Xoma's U.S. patent No. 4,918,163 is invalid? HasXoma proved that Centocor literally infringed Claim 7 of thepatent? Has Xoma proved that Centocor infringed Claim 7 underthe doctrine of equivalence? Does Centocor have an impliedlicense to the patent?

Gerald Sobel, lead counsel for Berkeley, Calif.-based Xoma,was first to present closing arguments. Donald Dunner, leadcounsel for Centocor, began his arguments late Tuesday and isscheduled to finish today.

Sobel told jurors that the patent is clearly valid because itdescribed for the first time the use of an antibody to treathumans. The patent was issued to the University of Californiain 1990 and licensed exclusively to Xoma.

"It's undisputed that (Lowell Young of UCLA) was the first oneto treat humans," said Sobel. "He won the race. As a reward forwinning that race, the Patent Office granted him the '163patent." Prior work by Nelson Teng, cited by Centocor, didn'tmake Young's work obvious, Sobel said.

Sobel said Claim 7 describes a method to therapeutically treata human with a gram-negative bacterial infection, using ananti-lipid A monoclonal antibody. That claim, Xoma said,covers Centocor's HA-1A antibody.

On the crucial infringement claim, the jury is being asked todecide whether Centocor's HA-1A and Xoma's E5 belong to afamily of antibodies that bind to an epitope on lipid A that ismost commonly associated with the endotoxin core.

Both sides have performed assays to determine whether HA-1A competitively inhibits E5 by binding to the same epitope.Xoma says they are the same. Malvern, Pa.-based Centocor saysthey are not.

Centocor also infringed under the doctrine of equivalence,Sobel argued, because of reverse inhibition: E5 competitivelyinhibits HA-1A, now sold as Centoxin.

Finally, Sobel argued that a 1984 licensing agreement withStanford University covers only the HA-1A antibody and did notgive Centocor an implied license to the '163 patent.

In his turn, Centocor's Dunner charged that "we wouldn't behere today if in 1989 Xoma hadn't realized that its clinicaltrials weren't going as well as it would have liked and that itwasn't going to be able to compete effectively with Centocor."

Centocor stock (NASDAQ:CNTO) was up 88 cents to $52.38 onTuesday. Xoma (NASDAQ:XOMA) was unchanged at $16.50.

-- Karen Bernstein BioWorld Staff

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