By Turna Ray
Researchers in the European Union are keeping a close eye on the outcome of the American Civil Liberties Union/Public Patent Foundation's anti-gene patenting case against Myriad, according to one of the main instigators of an opposition effort that resulted in narrowing the claims of a key European BRCA patent two years ago.
Gert Matthijs, head of the molecular diagnostic laboratory at the University of Leuven Hospital in Belgium, believes that if the US Southern District Court of New York's initial decision holds up on appeal, it could inspire researchers to take a similar anti-gene patenting case to the European Parliament.
"If the reasoning and decisions in the US are confirmed after appeal, then the European Parliament will hopefully take its own initiative and change its own law [on gene patenting]," Matthijs told Pharmacogenomics Reporter this week. "It's obvious that if all of a sudden the patentability of genes in the US will be adapted according to the current decision, then Europe will or should follow."
The Southern District Court of New York determined this week that seven patents on BRCA genes held by Myriad Genetics were invalid. The ruling is the result of a lawsuit filed last May by the ACLU and PUBPAT on behalf of several scientific organizations and women's health groups, charging that the BRCA gene patents held by the University of Utah Research Foundation and exclusively licensed to Myriad "stifle research that could lead to cures and limit women's options regarding their medical care" (see related story).
The far-reaching decision — in which Judge Robert Sweet held that isolated DNA was unpatentable because it is the same as naturally occurring DNA inside the body, but distinct in nature from all other chemical and biological molecules — came as a surprise since most legal analysts had deemed ACLU's case a long shot.
"I'm grateful that my American colleagues have taken the step to go to court in the US, and I'm even happier about the result," Matthijs said. "I don't know if any organization is sitting around waiting to take up this cause in Europe. But we should try to get it going." For a similar effort in Europe, Matthijs explained that a group like the European Society of Human Genetics would have to bring the issue before the European Parliament.
A decade before the ACLU and PUBPAT took up the cause of researchers and patients claiming Myriad's BRCA gene patents restricted research and access to tests, European geneticists were attempting to stymie the impact of BRCA patents on their research. They were successful up to a point, but the structure of the European patent system barred them broadly challenging gene patents in the way the ACLU and PUBPAT have in the US
Myriad was granted European Patent No. EP 699754 in May 2001 to protect methods for using the BRCA1 and BRCA2 genes for diagnosing predisposition to breast and ovarian cancer. Later that year, a number of parties, including several French research institutes and various national centers for human genetics, filed an opposition to the patent. That opposition led the Opposition Division of the EPO to revoke the patent.
Myriad appealed the decision, requesting that the patent be maintained in a form that restricts the original claims. Two years ago, the EPO's appeals board ended a seven-year tussle between Myriad and a number of European research groups by deciding to maintain the patent in an amended form [see PGx Reporter 12-0-2008]. Matthijs, as a member of the ESHG, was among those who took part in opposing Myriad's patents with the EPO.
[ pagebreak ]
In the end, the EPO amended the patent to cover frame-shift mutations, but not missense mutations, in the BRCA1 gene. Shift mutations account for approximately 60 percent of pathogenic mutations in the BRCA1 gene. The narrowed patent, which could not be further contested at the European level after the EPO's 2008 decision, does not, however, “contain claims directed to the BRCA1 gene itself or to mutated forms thereof,” according to the EPO.
"In Europe, even if we opposed the patenting of genes per se, we were kind of forced to play within the rules of the European patenting system," Matthijs recalled.
While patents in the US are challenged through the courts, in Europe, patent disputes are handled within the European Patent Office, the body responsible for granting and denying patents.
"When the EPO grants a patent, with which someone disagrees, he can file an opposition, and this is dealt with within the patent office," Matthijs explained. "Even if we had the kind of reasoning as our American colleagues in terms of non-patentability of genes, we were bound to play within the rules. All we could do was attack [Myriad's patents] on a technical basis."
Even after Myriad's patent was amended, "essentially nothing changed with regard to how EPO looked at patents." When European researchers brought their opposition to Myriad's patents before the EPO, they were told to avoid arguments on the ethics of gene patenting.
"If we had issues with the ethical and societal aspects, [the EPO said] we had to take it up at a political level and not to the patent office," Matthijs said.
Essentially, in order to challenge the patentability of genes as a whole, a group such as the European Society of Human Genetics would have to ask for a change in the law, at the level of Parliament, not just affect a change in the way the law is being applied. Under European law, isolated DNA is considered patentable subject matter, just as in the US, where the USPTO has granted numerous gene association patents.
"The decision in the US has more far-reaching impact than in Europe, even though we were happy with the result in the sense that the patents were effectively slimmed down in response to our action," Matthijs said.
However, he pointed out that while Myriad's patents are still enforceable in the EU to a degree, the company hasn't taken any labs to court for infringement. "We were waiting to see if Myriad ... would take us to court in Europe," Matthijs said. "Infringement is dealt with in court, but there hasn't been a single court case on the breast cancer genes, yet."
In response to charges that Myriad's gene patents have constrained third-party research on BRCA genes, Myriad has often asserted that despite its strong IP position, it has promoted and subsidized research on BRCA mutations.
In court documents, Myriad claims that more than 18,000 scientists have researched BRCA1 and BRCA2, and published over 7,000 papers on the genes. The company says it has invested more than $200 million in promoting patient access to BRCA testing, resulting in 400,000 people being tested for BRCA mutations throughout the US.
However, Matthijs cites a few other reasons for the lack of patent infringement cases involving Myriad's BRCA patents in Europe. For one, the complexity of the EU system may have made it difficult for Myriad to track patent infringement in Europe.
"They have clearly expressed the intent to come after [European labs] infringing the BRCA patents eventually," Matthijs said. "Why this has not happened, I would say, is because their patents have been weakened, and they have to attack individual labs in individual countries. It would take them into several court cases.
"At the individual lab level … it's probably not worth it for Myriad to pursue these infringement cases," he added. "After this decision in America, we feel a little more relaxed than we were before."
[ pagebreak ]
Additionally, Myriad seems to be just starting to penetrate the European market with its BRACAnalysis test and other diagnostic products.
In a March update on its business to investors, Myriad CEO Peter Meldrum said the company is planning to establish a presence in Europe by 2012. While Meldrum estimated that the European diagnostic market represents about 75 percent of the size of the US market, "today only about 5 percent of our revenues come from Europe," he said, emphasizing that there are significant market opportunities on the other side of the pond [see PGx Reporter 03-10-2010].
State-side, Robert Cook-Deegan, director of Duke University's Center for Genome Ethics, Law & Policy, pondered whether US courts would ultimately end up maintaining Myriad's patents, but in a narrower form, as it happened in the EU.
"I could easily imagine the courts saying [on appeal] that some of these claims are so broad that they really shouldn't have been granted, and then ending up with something that looks like the European patents on BRCA 1 and BRCA 2," Cook-Deegan told PGx Reporter. "But you can't get there directly from this case [at the district court level]. That would have to be decided in higher courts."