BRCA1 patent decision may be ignored in clinics.
It has been one of the toughest, and most impenetrable, biological patent cases in the history of the European Patent Office. But the University of Utah in Salt Lake City has finally won its battle to keep some European patents on BRCA1 — a gene associated with breast and ovarian cancer.
The ruling means that the patent owners now have the right to collect royalties on tests carried out on tens of thousands of women across Europe every year. The tests identify those who have a high risk of developing breast cancer because they have a mutated BRCA1.
"It is disappointing after our 7-year fight even though we have managed to reduce the scope of the patents," says Dominique Stoppa-Lyonnet, a clinical geneticist at the Curie Institute in Paris. "We had all been freely testing the BRCA genes since they were first described in the early 1990s," she says.
Between 10% and 15% of all heritable breast and ovarian cancers have a mutation in BRCA1 or BRCA2, another gene linked to breast cancer, leading to as many as 5,000 new cases of both cancers in the European Union every year.
An inexact sequence
Clinical geneticists do not agree with monopolies on diagnostic testing of genes for such diseases because they believe they block the competition that could lead to the development of better, cheaper products. Some of those contacted by Nature say that they will continue to test for the mutations in defiance of the patent.
Gert Matthijs, who heads the Centre for Human Genetics at the University of Leuven in Belgium, says that no European clinic has paid royalties for BRCA1-related diagnoses since the European Patent Office first granted three BRCA1 patents to the biotech company Myriad Genetics in 2001. Myriad, which is based in Salt Lake City, transferred ownership of the patents to the University of Utah in November 2004. It was facing growing opposition to its patents from genetics societies, research institutes, hospitals and some governments.
In 2004, the European Patent Office revoked the key patent covering any mutations in BRCA1, as well as any diagnostic method for their detection. Its oppositions board, which considers patent challenges, was convinced by arguments that Myriad had registered an incorrect gene sequence when it first filed the patent in 1994 — and that a perfect reference sequence is required to make a full diagnosis.
But the office's highest board of appeals reversed this decision on 19 November, after the patent owners said they would reduce the scope of the patent to cover only 'frame-shift mutations'. These mutations — usually the deletion or insertion of one or two nucleotides — lead to the wrong sequence of amino acids being translated from the gene.
This board, whose ruling is final, agreed that an exact sequence is not required to detect these 'frame-shift' mutations — which account for around 60% of those associated with breast and ovarian cancer.
But clinical geneticists say that the ruling is confusing because the patent now applies only to some of the genes picked up during diagnosis. "It becomes unclear at which point during the analysis practitioners like myself would start to infringe the patent," says Matthijs. The University of Utah declined to say whether it will now seek out and challenge infringers, which it had not done while the patent oppositions were ongoing.
The patent owners have chosen to pay the fees needed to maintain the patent only in large European countries. It will not apply in Belgium, for instance, says Matthijs, "but it is applicable in neighbouring France and the Netherlands, where testing could now start to cost a lot more".
Myriad holds very broad patents on both BRCA1 and BRCA2 in the United States, where it charges US$3,120 for a full analysis of both genes and $460 for a single mutation test. The single test is used mainly by members of families in which a mutation has been detected before. In Europe, the tests are usually done in large academic institutions and hospitals at a cost of up to €1,500 ($1,900) for both genes. "We will wait to see what royalties the University of Utah might demand of us, but it won't stop us testing the gene in France," says Stoppa-Lyonnet.
William Hockett, a spokesman for Myriad, says that the company is keen to discuss the test's costs with national health systems, pointing out that "our analysis is covered by insurance in the United States because it is highly cost-effective to the insurers".
The patent office granted Myriad a broad patent on BRCA2 in 2003. That patent was reduced in scope to cover just one mutation, common in Ashkenazi Jews, in 2005. Myriad is challenging a second, broader, patent on BRCA2 that is co-owned by the charity Cancer Research UK. Mike Stratton of the Wellcome Trust Sanger Institute in Cambridge, UK, who is one of the inventors behind the patent, says that they "took out the patent to defend the gene against other patent approaches. We offer free licensing to any reputable laboratory who wants to use it," he says.
About this article
The biotechnology sector and US gene patents: Legal challenges to intellectual property rights and the impact on basic research and development
Science and Public Policy (2012)
Annals of Human Genetics (2011)