A federal judge in San Francisco ruled last week that the patent for the naturally occurring form of the widely used reagent Taq DNA polymerase was fraudulently obtained and is thus invalid.
The decision could mean increased competition leading to cheaper reagent prices, as well as legal action to recover unnecessary costs. And, depending on future court rulings, the patent dispute may also undermine a related patent for the DNA-amplification process of PCR (polymerase chain reaction).
The judge ruled that the US Patent and Trademark Office was misled a decade ago by scientists from the Cetus Corporation, which was bought by the Swiss company Hoffmann-La Roche in 1991 (see Nature 397, 460; 1999). Roche purchased the Taq patent as part of the deal.
The ruling was issued in a long-running federal lawsuit in which Roche originally accused the Promega Corporation of infringing its patent by selling its own native Taq to researchers. This lawsuit began after a disagreement between Roche and Promega over Taq licensing terms. Promega, a privately held Wisconsin company, is also involved in challenging Roche's patent in Europe.
After hearing evidence earlier this year during a trial in San Francisco, US district judge Vaughn Walker ruled that there were eight instances in which Roche scientists had engaged in “inequitable conduct” with “intent to mislead” to secure the Taq patent.
These involved misstatements or the withholding of scientific information during the patent office's review process. They included withholding details about how Taq binds in a phosphocellulose column, misleading statements about Taq's fidelity compared with previously described enzymes, and presenting a key experiment as having been performed when it had not been done.
In his ruling, Walker likened the conduct of Roche scientists to “scientific misconduct”. Roche officials deny that their scientists engaged in impropriety, and say they plan to appeal. And they insist their other patents are not affected or threatened.
The judge will hold a hearing next month to begin the process by which Promega will seek financial remedies in the case. If his ruling stands, Roche's patent for native Taq will be void and unenforceable.
He ruled that all claims of Roche's patent are unenforceable. The patent includes three claims, one of which is for the native Taq and another for recombinant Taq. Therefore, Promega argues, Roche's patent covering both native and recombinant Taq is unenforceable.
Furthermore, because the judge has ruled that Roche's patent is unenforceable for Taq, Promega attorneys plan to argue that Roche's patent on PCR, which relies on the use of Taq, is also unenforceable. But Roche disputes this, saying the ruling only affects native Taq, which is used by a much smaller proportion of the research community for PCR reactions.
Among the issues expected to come out of the case are Taq pricing, the amount Roche is now alleged to have received improperly under its patent, and reimbursement plans.
For instance, Taq was sold by some biotech firms for around 16 cents per unit before Cetus was granted its patent in 1989. Taq is now sold for at least 30 cents per unit by companies licensed by Roche. These companies pay Roche 15 to 17 cents per unit, claims Promega attorney James Troupis.
The biotech community is speculating on who will try to recover what funds. US government agencies such as the National Institutes of Health (NIH), the National Science Foundation and the Department of Energy are huge purchasers of Taq, either directly or through grants to scientists and universities.
Taq is reportedly the most-purchased reagent under NIH grants. Agency officials decline to say what actions might be taken to recover any funds, pointing out that a decision on such legal action would come from the US Department of Justice. Justice officials were unavailable for comment.
Meanwhile, at least one other company, New England Biolabs of Massachusetts, is considering re-entering the market to offer Taq (see Nature 390, 327; 1997). Its decision, combined with the elimination of Roche's royalty fee, may lead to cheaper pricing for Taq. But Roche insists the judge's decision will have little financial impact because the company believes the recombinant Taq patent is unaffected.
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Stabilization ofTaq DNA Polymerase at High Temperature by Protein Folding Pathways From a Hyperthermophilic Archaeon,Pyrococcus furiosus
Biotechnology and Bioengineering (2006)