san francisco

The seven-year battle over ownership of rights to the enzyme Taq DNA polymerase came back to court this month.

A San Francisco court will hear allegations that the US patent held by Swiss drug company Hoffmann-La Roche was fraudulently obtained by the original applicant, Cetus Corp. Roche is being challenged by Promega Corp, a laboratory supply company based in Madison, Wisconsin, which has been selling Taq since the late 1980s under a licence granted by Cetus.

The dispute dates from Roche's1991 purchase of the rights to the polymerase chain reaction (PCR) from Cetus in a $300 million deal. At the time, the Swiss company asked Promega to stop selling Taq, claiming it violated the Roche-Cetus agreement. When Promega refused, Roche demanded higher royalties. Promega again refused, and in 1992 Roche filed a suit for breach of contract. The contract expired in 1995.

In November 1996, Roche received a broad European patent covering key PCR enzymes including Taq. At the time, company officials said the approval showed that expert scientific examiners recognized the biochemical facts that distinguish the Cetus invention from prior work. A year later, however, the Australian Patent Office withdrew rights to the enyzme in its native form, in response to a challenge led by New England Biolabs and Bresatec (now Bresagen) on the basis that other researchers knew of Taq before Cetus made its claim (see Nature 390, 327; 1997). The Australian Patent Office upheld Roche'sclaim to recombinant Taq.

Promega argues that Roche'sTaq patent is invalid because Taq had been anticipated by earlier work. Its lawyers claim that Cetus was aware that the thermostable DNA polymerase it had extracted from E. coli was the same as enzymes from the same organism that had already been described in the literature, and so deliberately misled the US Patent and Trademark Office.

The US District Court Judge Vaughan Walker had ruled in 1996 that Taq inventors made four material misrepresentations or omissions in their patent application that could have misled patent examiners. Now he must decide whether those misrepresentations were intentional, and if Cetus scientists and executives knew their invention was not novel and withheld information.

Proceedings began on 1 February with Arthur Kornberg, winner of the 1959 Nobel Prize in Medicine, on the witness stand. As he explained the isolation of DNA polymerase, Judge Walker — in what has become a leitmotiv — urged participants to stick to the point. In cross-examination, Roche lawyers then showed that two of Kornberg'sexhibits included erroneous details.

More cut and thrust can be expected in the two weeks scheduled for the trial. Using internal memos and expert testimony such as Kornberg's, Promega hopes to show that David Gelfand, the primary inventor on the Taq patent and manager of the Taq project at Cetus, misrepresented facts about Taq activity, nuclease contamination, measured fidelity, pH profile and other characteristics that Cetus used to show the invention was novel.

Promega plans to lay out 13 instances of misrepresentation or material omission in the patent filing. The documents and other information show that “the inventors chose to mislead, misrepresent and omit critical information time and again”, writes attorney James Troupis in Promega'strial brief.

Roche responds that the applicants either did not know about the undisclosed information or did not believe it was important. The Cetus discoveries were distinct from earlier ones and the scientists involved are innocent of deception, writes Roche attorney Brian Poissant, adding that some exaggeration and advocacy in a patent claim does not amount to fraud.