Applera lost its real-time PCR instrumentation patent in Europe last week on a decision by the European Patent Office’s Opposition Division that hinged on a single document and witness testimony.
There were five opponents to the patent, including Bio-Rad Laboratories, MJ Research — a Bio-Rad subsidiary since August — and MJ distributor Biozym, all of whom were barred from manufacturing and selling RT-PCR thermal cyclers in Germany in June after Applera’s Applied Biosystems unit obtained injunctions against them in German court. The injunctions, based on a German patent that corresponds to the European patent, may be lifted, although Applera will oppose any attempt to do this, a company spokeswoman told BioCommerce Week.
“I think economically, it’s a big loss for Applera in Europe,” said Mathias Ricker, a patent lawyer for Jones Day in Munich who represents Eppendorf, another opponent in the case. Certainly, it introduces uncertainty into Applera’s ability to control the market.
The battle over Applera’s European RT-PCR patent is part of a positioning for the emerging market to follow the expiration of the first PCR patents in March 2005 in the US and March 2006 in Europe. In filings with the SEC, ABI said that it expects a possible reduction in its PCR royalties beyond 2005 to be offset to a “substantial degree” by income from real-time PCR and other related technologies that should mitigate the effects of the patent expirations.
ABI measures the core PCR market at $600 million a year.
RT-PCR technology brings quantitation to the PCR process, allowing the collection of real-time measurements during the amplification period. The therrmal cycler measures fluorescence resulting from the reaction of the chemistry and the sample. RT-PCR thermal cyclers are relatively early in commercial development. A Frost and Sullivan study from 2002 estimates thermal cycler sales growing more than 200 percent to $776 million by 2006 from $252 million in 2001.
The other opponents to Applera’s European patent are Bibby Sterilin of Stone, UK, and the Intellectual Property Rights Group of the UK’s Secretary of State for Defence.
Cepheid, an initial opponent, withdrew its opposition in June.
Applera said in a press release last week that it intends to appeal the EPO’s decision. Given the usual timeline of the EPO’s Boards of Appeal, a final decision is unlikely to be reached before the end of 2006, according to Ricker.
The patent, EP0872562, is entitled “Instrument for monitoring nucleic acid amplification reactions” and was granted in late 2002. The sole inventor is Russell Higuchi of San Francisco. F. Hoffmann-La Roche, the original applicant, transferred the patent to Applera in early 2003. Later that year, the oppositions were filed.
The EPO revoked Applera’s patent because of a single report containing prior art that it determined was distributed to a number of scientists at an international workshop in Germany about two weeks before the patent application was filed. Also, the scientists were not asked to keep the contents of the report confidential.
Applera and the opponents disagreed on whether the document, a report that has not been published in a journal and that is not available from any library, was available at the workshop. “The issue was basically, was this document indeed distributed to the participants?” Ricker said.
“We don’t consider [the document] admissible, it wasn’t published,” Ana Kapor, an Applera spokesperson, told BioCommerce Week.
Both parties filed conflicting affidavits from scientists involved with the conference, said Ricker.
To clarify matters, the Opposition Division called on Christof Biebricher, a professor at the Max Planck Institute for Biophysical Chemistry in Göttingen, during oral proceedings last week.
Biebricher attended the workshop, entitled “Selection — Natural and Unnatural in Biotechnology.” The meeting, which was organized by Nobel Laureate Manfred Eigen, took place April 18-20, 1991 at the Max Planck Institute. The patent application has a priority date of May 2, 1991, meaning it was first filed that day. Biebricher testified that the document, “Report on Evolution of Research,” was distributed to scientists at the meeting, according to Ricker.
The report, written by Eigen and other scientists, is pivotal because contains the concept for an instrument to carry out online PCR. The description was deemed by the Opposition Division, to be clear and precise enough to fall “squarely within the claims of the [Applera] patent,” said Ricker. “Basically, it was novelty-destroying.”
Applera’s lawyers complained that the opponents’ request for Biebricher to appear as a witness was made too late, and asked for the oral hearing to be adjourned so they could reply to his testimony. However, their request was rejected by the Opposition Division. According to Ricker, the opponents offered the witness two months before the hearing, as required by the EPO.
Affect on US Patent
Applera’s US patent on RT-PCR instrumentation, No. 6,814,934, entitled “Instrument for monitoring nucleic acid amplification,” was granted on Nov. 9. That same day, the company sued Bio-Rad, MJ Research, and Stratagene for infringement. This patent, which also bears Russell Higuchi as the sole inventor, is unlikely to be affected by the EPO decision, Ricker said. According to US law, neither the filing date, nor priority date, but the date the invention was actually made is relevant. “[Higuchi] has already sworn behind the date of publication of this reference,” Ricker said.
But if the European patent stays revoked on appeal — or even earlier — Applera could be held liable for ptoential damages suffered by Bio-Rad and MJ Research, from the injunctions issued against them.
Another still pending European patent application on RT-PCR, EP1256631, filed by PerkinElmer in 1992 and transferred to Applera in 1992, is also likely to be affected by the decision.
On Jan. 7, EPO patent examiners said that the application “bears remarkable similarity in its scope to the parent application,” the European patent revoked last week.
The examiners suggest that a decision on the application be postponed until the outcome of the opposition to Applera’s patent is determined.
— Julia Karow ([email protected])