Raggio-Italgene SPA is disputing Temple University's decisionthis week to terminate its license to the Italian company forTemple's c-myb and c-abl oligonucleotide inventions.

Temple said Raggio breached the licensing agreement,originally signed in January 1991, and did not satisfy theobligations of the contract.

Specifically, Temple said Raggio

-- Failed to perform specific obligations under the license,including not supplying the university with working antisenseoligonucleotides

-- Did not secure a suitable partner for oligonucleotidechemistry and production

-- Did not make required payment in support of ongoingresearch

After Temple terminated its license with Raggio, LynxTherapeutics Inc., the therapeutics division of AppliedBiosystems of Foster City, Calif., said it will exercise anoption to exclusively license the c-myb and c-abl inventions.

Giovanni Cozzone, chief executive officer of Raggio-Italgene inRome, said that Raggio did supply Temple witholigonucleotides and made payments to the university. He saidRaggio and Temple agreed upon a chemical producer, but theuniversity refused to deal with the producer. "We felt we keptour part of the bargain," he told BioWorld.

Cozzone also said that Raggio tried to settle the dispute withTemple, but the parties were unable to reach an agreement.Raggio then began discussions with Lynx and, Cozzone said,reached an agreement. Cozzone said he had presumed thatTemple would "sign off" on the agreement, but that Raggio'scounsel received additional demands from the university.

Antonio Goncalves, vice provost for research for Temple inPhiladelphia, said Raggio never responded to the proposals theuniversity made after Raggio and Lynx reached theiragreement. On April 21 Temple sent Raggio a notice of breachof contract for non-delivery of the oligonucleotides specifiedin the license agreement, Goncalves said.

He said the license agreement required Raggio to supply theuniversity with 100 mg. of the sense and antisense compounds,but Raggio only sent 5 mg. of each, and they were cytotoxic.Raggio and Temple tentatively agreed upon a chemicalproducer, Goncalves said, but the university decided thatproducer was not suitable when the oligonucleotides theuniversity received did not work. Goncalves said a formalagreement concerning the producer was never signed.

He added that although Temple received its first two quarterlypayments this year, the payments stopped after that.

The c-myb proto-oncogene oligonucleotide regulates cellgrowth and differentiation in a variety of tissues, notablyblood vessel walls. A fragment of c-myb was shown, in a studyreported in the Sept. 3 issue of Nature, to inhibit theobstructive buildup of arterial smooth muscle cells in rats andrabbits.

"These studies constitute the first reported use of antisenseoligonucleotides to inhibit synthesis of a normal gene productunder in vivo conditions, with a subsequent effect on a cellularprocess," wrote researcher Robert D. Rosenberg of theMassachusetts Institute of Technology.

The c-myb oligonucleotide has "a high value from a commercialstandpoint," said Raggio-Italgene's Cozzone. "These rightswould put a company in a strong position."

Cozzone said he still hopes to reach an agreement with Temple.

Goncalves, however, said Temple has terminated its agreementwith Raggio and "would not be surprised" if the disputeproceeds to litigation.

-- Chuck Lenatti Managing Editor

(c) 1997 American Health Consultants. All rights reserved.