The U.S. Court of Appeals for the Federal Circuit on Monday reverseda 1990 jury that ruled Genetics Institute Inc.'s novel tissueplasminogen activator (NPA) infringed on three t-PA-related patentsheld by Genentech Inc.Tom DesRosier, vice president and chief patent counsel for GeneticsInstitute, told BioWorld that the ruling opens up a range of options forGenetic Institute's development of NPA, from taking the clot-busterinto the clinic to licensing it out. Genetics Institute has rights to NPAeverywhere except Japan and other parts of Asia, where Tokyo-basedSuntory Ltd. has licensed the molecule and has it in clinical studies.Genentech, which had 1993 t-PA sales of $236 million, said it isreviewing whether to seek reconsideration by the Court of Appeals.Stephen Raines, Genentech's vice president, intellectual property, toldBioWorld the company also could request a hearing before all judgeson the Court of Appeals for the Federal Circuit. A final option wouldbe to ask for review by the Supreme Court.Raines said Genentech would first review court documents, then assesswhether NPA is a strong enough potential competitor to merit takingany action. Genetics Institute, of Cambridge, Mass., believes it is."There's a very clear physical difference between the two molecules,"Dennis Harp, Genetics Institute's corporate communications director,told BioWorld. "The NPA molecule has about a fifth of its amino acidsequence removed from t-PA. It was specifically engineered to increaseits half-life over the half-life of t-PA."Genentech, of South San Francisco, said it has made scientificadvances in its t-PA program since 1990, and also has strengthened itsposition with the issuance of a patent "covering a t-PA moleculehaving a large number of amino acids removed," Raines said. "We arewell-advanced with our second generation product, which we feel hasmany advantages."G. Kirk Raab, Genentech's president and CEO, said the secondgeneration product should be in "clinical trials by the beginning of nextyear, and based on preliminary studies, promises an improved safetyand efficacy profile based on its fibrin specificity."Genentech has had its t-PA patent revoked in England, is involved inappeal procedures in the rest of Europe, and is in a second patentprocedure in Japan (after removing one company from the market).DesRosier said Suntory "does not have any concern (in Japan) aboutthe Genentech patent. We're very confident the Genentech t-PA patentwill not pose a problem in them going to market." He said the Suntoryclinical data _ from Phase I and II trials _ may be helpful, dependingon the FDA's outlook, when Genetics Institute or another companyseeks to take NPA in the clinic in the U.S.DesRosier said evidence from animal data presented in court showedNPA has a 10-fold longer half-life than t-PA. And that repeatedadministration wouldn't be necessary with the Genetics Instituteproduct.Raines said Genentech has filed with the FDA for a bolus-likeadministration of t-PA, and Raab said there is a labeling change beforethe FDA requesting accelerated dosing. Raines said a longer half-lifecould present safety problems.Last week, Genetics Institute was issued a patent coveringpharmaceutical compositions of erythropoietin (EPO), for which thecompany was enjoined from making, using or selling in the U.S. as aresult of a dispute with Amgen Inc., of Thousand Oaks, Calif. GeneticsInstitute followed the decision by suing Ortho Pharmaceutical Corp.,an Amgen licensee, and is considering whether to take action againstAmgen, which also holds EPO patents. n

-- Jim Shrine

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