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PCR Licensing Deal Validates Roche IP; Bolsters Life Tech's Ongoing Push into IVD Market

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By Ben Butkus

Roche and Life Technologies have entered into a pair of licensing agreements that confer to Life Tech rights to use various PCR, real-time PCR, and high-resolution melting curve analysis technologies for human diagnostic applications, Roche said this week.

The agreements serve as one of the most tangible indicators to date of Life Tech's intention to move into the human in vitro diagnostics space, a market it has been eyeing for several months on multiple technology fronts. While the company has had a longstanding agreement with Roche regarding the PCR IP, it has to date been limited to the research and applied markets.

For Roche, the deal is a "huge statement" about the validity of its PCR patent portfolio, which has been under attack on multiple fronts over the past several months, Monte Wetzel, head of licensing at Roche Molecular Systems, told PCR Insider this week.

"It's really interesting that at this point in time Life Tech should take these two licenses," Wetzel said. "I think it speaks volumes to the Roche PCR portfolio and the legs that portfolio has."

Under the agreements, Roche has granted Life Tech an in vitro diagnostics product license to all of Roche's patents for real-time PCR, as well as to other important PCR-related technology in the diagnostics field. The agreements also cover reagents and methods of using SYBR Green I fluorescent dye technology, melting curve analysis for real-time PCR, and the use of high-resolution melting-curve analysis for diagnostic applications.

Financial terms of the agreement were not disclosed. In a statement, Roche referred to the agreement as a "settlement," a term that Roche's Wetzel said did not necessarily signify that there had been a legal argument between the parties.

"We didn't go to court over the subject matter that we licensed," Wetzel said. "We had some questions about … how we interacted with each other, and … we spent some time … and settled those questions. There were no legal battles or court involvement. We just got together and sat down and talked."

Long and Winding Road

The patent portfolio at the heart of one of the licensing deals has experienced a "winding, curvaceous history," according to Wetzel. Many of the technologies described in the original subject PCR and qPCR patents were developed in the 1980s and early 1990s at Cetus. Roche acquired the rights to those patents from Cetus in 1991 and formed its Roche Molecular Systems division to develop and disseminate the technology.

Roche continued to improve upon many of those original patents and also filed new patents surrounding PCR and qPCR, resulting in an "extensive portfolio … involving several hundred patents," Wetzel said.

In the early 2000s, Roche and Life Tech predecessor Applied Biosystems were involved in a series of licensing agreements and legal battles for many of the PCR technologies, culminating in a 2005 settlement agreement under which Applied Biosystems gained the ability to exclusively use and outlicense Roche patents covering reagents and methods to practice PCR and real-time PCR in research and applied fields.

Meantime, Roche retained the rights to use the patents in any application — but was only allowed to outlicense the patents for diagnostics and diagnostics-related research and not for basic research and applied markets. However, it can and still does use the patents for its own basic research purposes.

"We're the patent owners — we have full rights to be able to use all patents in any field we want," including research, Wetzel said this week. "We can't license, but we can make research kits and so on."

The second licensing deal between Roche and Life Technologies involves HRM technology, a technique used to analyze PCR products. In HRM, after amplification, resulting PCR product is slowly heated. Each double-stranded DNA has its own specific melting temperature, or Tm, defined as the temperature at which half of the DNA becomes single-stranded. By measuring Tm using an intercalating dye, variations in the amplified DNA can be identified.

Roche outlicenses this technology in cooperation with Idaho Technology. This arrangement dates back to the late 1990s when Boehringer-Mannheim inked an exclusive license with Idaho Tech to use HRM in real-time PCR applications. Roche subsequently acquired Boehringer-Mannheim, thus inheriting the exclusive license.

"The situation … is similar to the Roche [qPCR] portfolio [in that] Roche licenses that IP out in the diagnostics field … and Idaho can license it out in the research field," Wetzel said. "So, in addition to the Roche-generated patent portfolio that Life Tech needed access to, Life also needed access to the real-time PCR-related IP that is owned by Idaho, but also controlled in the diagnostics field by Roche."

Notably, in 2010 Life Tech and Idaho Tech signed their own cross-licensing pact covering a range of PCR technologies, including the rights to the TaqMan and SYBR Green chemistries. Specifically, Idaho licensed from Life Tech's Applied Biosystems division the right to use the TaqMan 5' nuclease process, while ABI licensed from Idaho the right to use SYBR Green in PCR (PCR Insider, 1/28/10).

IP Validation

As many of Roche's original PCR patents have expired or are expected to expire in coming years, industry insiders have predicted that the company will soon no longer be able to reap the financial benefits of outlicensing the patents.

In addition, both Roche and Life Tech's PCR-related patents have come under fire over the past several months from multiple fronts. For instance, intellectual property watchdog firm Troll Busters in June filed a request with the US Patent and Trademark Office to reexamine one of the key Roche PCR patents. This followed a similar challenge it filed against another Roche PCR patent in 2009, and is part of a broader strategy by TrollBusters to challenge a "PCR patents duopoly" enjoyed by Roche and Life Technologies (PCR Insider, 6/23/11).

In addition, Roche recently initiated arbitration against Cepheid in response to Cepheid's disclosure in October that it was prematurely terminating its PCR license with Roche after "determining that any patents remaining under the license are not pertinent to Cepheid's future business plans." (PCR Insider, 2/9/12).

Experts have also surmised that the last major PCR patent in Roche's portfolio is expected to expire in 2017, which may embolden companies wishing to practice methods covered by the patents to willfully infringe. In February, a member of Roche's legal team called that synopsis a "inappropriate characterization" of Roche's patent portfolio but did not provide further details on the expiration dates of key patents.

Now, in the face of these challenges, Roche sees the Life Tech licensing agreement as validating its PCR patent portfolio and its application to diagnostics.

"Life Tech has been licensing these patents out [for research] for quite a few years now, and I think of all the companies in the world, they would know the Roche patent portfolio best," Wetzel said. "And since they did go ahead and take a license at this point in time — with all the press about patent expirations and Roche and so on — I think it makes a huge statement."

Life Tech's Dx Play

It is unclear how Life Tech plans to proceed in terms of developing qPCR and HRM-based assays for the IVD market. Reached by e-mail, a spokesperson for Life Tech said that the company declined to comment on the agreement at this time.

However, Life Tech has been making overtures for some time about its intentions to enter the molecular diagnostics arena, and its collaborations and deal-making in this area have been steadily on the rise, particularly in the area of qPCR.

In 2008, the company received 510(k) clearance from the US Food and Drug Administration for its 7500 Fast Dx Real-Time PCR Instrument for use with the new CDC Human Influenza Virus Real-time PCR Detection and Characterization Panel from the US Centers for Disease Control and Prevention. In addition, the 7500 Fast Dx in 2010 garnered the CE Mark for IVD use in Europe (PCR Insider, 3/25/10).

Last summer Life Tech flexed its IVD muscles when, in response to the outbreak in Germany of a deadly antibiotic-resistant strain of E. coli, it teamed with University Hospital Münster to quickly sequence the strain using the Ion Personal Genome Machine and develop a qPCR test kit for the strain to run on the 7500 Fast Dx instrument. Even though that test kit is for research use only, it showed how Life Tech could implement several of its technologies and expertise to quickly develop and validate a molecular diagnostic assay (PCR Insider, 6/9/11).

Also, in September Life Tech said that it had inked an agreement with Quidel to distribute and commercialize four of Quidel's molecular diagnostic assays for use on the ABI 7500 family of PCR systems in Europe (PCR Insider, 9/22/11); and in October the company signed a deal with GlaxoSmithKline to develop a qPCR-based companion diagnostic test for GSK's candidate cancer immunotherapy using Life Tech's TaqMan Array Card technology (PCR Insider, 10/26/11).

And, as reported by PCR Insider sister publication GenomeWeb Daily News, in January at the JP Morgan Healthcare conference in San Francisco, CEO Greg Lucier and other company officials noted the potential of Life Tech's qPCR and sequencing platforms for developing new molecular diagnostic tools; and said that the company had already begun reaching out to diagnostic firms to supply content for molecular assays.

Finally, also in January, Life Tech acquired AcroMetrix, a privately held supplier of quality control reagents for clinical laboratories, blood screening centers, and IVD manufacturers (PCR Insider, 1/14/10).

Life Tech has also been grooming some of its newer technologies, such as its Ion Torrent next-generation sequencing and OpenArray digital PCR platforms, for use in the clinical diagnostics space.

"In the last few months, Life Tech has been making it clear that they are entering the diagnostics business in the IVD field, and to do that they recognized that they needed … the licenses for the two sets of [PCR-related] IP," Roche's Wetzel said this week.

"We're very happy about this, and I know Life Tech is, as well, because now they have the freedom to operate that they need in the diagnostics space," he added.


Have topics you'd like to see covered in PCR Insider? Contact the editor at bbutkus [at] genomeweb [.] com.

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