On March 29, the United States District Court for the Southern District of New York delivered an opinion that surprised many, and threw the biotech industry into a frenzy of pushback: it ruled that the patents held by Myriad Genetics and the University of Utah Research Foundation on the BRCA1 and BRCA2 genes, which confer increased susceptibility to breast cancer, are invalid.
The patents have prevented anyone else from offering tests for these genes, or developing their own — which has given Myriad a monopoly over all BRCA testing in the US, a monopoly that allows them to charge more than $3,000 per test.
In a 152-page ruling in the case (officially known as Association for Molecular Pathology v. United States Patent and Trademark Office, but more commonly referred to as ACLU vs. Myriad Genetics), Judge Robert W. Sweet wrote that “because the claimed isolated DNA is not markedly different from native DNA as it exists in nature, it constitutes unpatentable subject matter.”
The ruling was applauded by several leading neurogeneticists, including Eric Hoffman, PhD, who directs the Center for Genetic Medicine Research and holds the James Clark Chair in Molecular Genetics at Children's National Medical Center in Washington, DC.
“I hold the patent on the gene for Duchenne muscular dystrophy, one of the most common genetic disorders,” he said. “I would be very happy to have that patent invalidated. For years, we had a nonexclusive license allowing anyone in the world, for a relatively cheap fee, to do the testing. But recently Children's Hospital of Boston, which owns the patent because it was my employer at the time, decided to make it exclusive and sell a license only to Athena Neurodiagnostics. So all the labs working in the field got a cease-and-desist order to stop testing; only Athena can do the test now.”
A RETURN FOR THE R&D INVESTMENT?
Industry representatives claim that patent rights are necessary to compensate them for their investment. Teepu Siddique, MD, a neurogeneticist at Northwestern University Feinberg School of Medicine who identified the gene responsible for the slowly progressive, early-onset form of amyotrophic lateral sclerosis (ALS) known as juvenile inherited ALS, finds that argument unpersuasive.
“The engine for discovery of genetics and genomics in this country has been our tax dollars,” Dr. Siddique said. “It's federally-funded work that produces the real breakthroughs. So you could make a case for some patent protection for a limited period of time — the duration of a grant period perhaps — but beyond that I think it should become the property of the public.”
Dr. Siddique holds a patent on that ALS gene he discovered — not because he wanted to, he said, but because the patent environment more or less forced him to. “But we made our mouse model widely available — any scientist can use it,” he said. “The issue is that we and others would be able to do more, and be more open, if the scientific enterprise weren't so closed, with such a promiscuous relationship between science and industry.”
“The goal of patents in general is to facilitate and encourage innovation and progress and developments,” Dr. Hoffman said. “But there's a point at which patent protections can cross a line and inhibit the same thing.” He added that he thinks that exclusive licenses like those held by Myriad definitely cross that line.
IS THE GENE PRODUCT CHANGED?
William Warren, chair of the Biotechnology and Life Sciences Team at the law firm Sutherland, Asbill, and Brennan, argues that Judge Sweet erred in declaring that isolated DNA is essentially unchanged from the original “product of nature”— something that the Supreme Court ruled years ago in cannot be patented.
“That ignores the other substantive fundamental changes that the molecule has undergone during isolation in order to make that DNA information available,' he said. In the diagnostic test, for example, they use isolated DNA probes, much smaller sequences, targeted to the relevant area. The DNA in its native state is not useful in the same way that it is when it's been isolated, so that while some of the information may be the same, it's been materially changed so that it can be used, and the judge didn't seem to appreciate that.”
Dr. Hoffman is skeptical of this rationale. “None of the sequences has changed. The gene didn't change. And they're making money by testing a patient's mutations, and those mutations certainly exist in nature and haven't been changed.”
PROS AND CONS FOR SCIENCE
Louis Ptacek, MD, the John C. Coleman Distinguished Professor in Neurodegenerative Diseases at the University of California-San Francisco, had a more mixed reaction to the ruling than did some of his colleagues. Although he turned down an offer to testify on behalf of Myriad in the case, he can see both the pros and cons for science if gene patents are broadly declared invalid.
“It's very complicated,” he said. “You can understand diagnostic companies wanting exclusive patents so that if they develop tests, they can make money. But then they can charge anything they want. This has been a big issue in neurogenetics, with companies like Athena being able to really gouge the patient or insurer because they have exclusive patents. So I think this decision is a real victory for patients and for affordable health care.”
But he is concerned that, on the other hand, companies won't have the incentive to develop diagnostic tests for rarer diseases at all. “Breast cancer is so common that BRCA is a test everyone will want to offer. This ruling will make it possible for other companies to get into the market, and competition will drive the price of the tests down. The question will be who can do the highest quality testing at the most affordable price, and people will still make money.”
That may not be the case, Dr. Ptacek worries, for more “orphan” diseases. “Companies won't be able to make enough money on them,” he said.
Dr. Hoffman doesn't think invalidating patents will make much difference to rare disease diagnostics. “Even now, the large majority of patents don't generate any money, period,” he said. “Only a small fraction are even licensed from universities, and an even smaller number are making money. The only way you're going to make money on a rare disorder is if you use that genetic information to develop a therapy. That is different, and then you're going to patent a drug. That's what drives research.”
Of course, the New York court ruling is far from the final word on the matter. Myriad is expected to appeal the decision, and it seems likely that the case may eventually end up before the US Supreme Court.
If the highest court in the land strikes down gene patenting, it won't exactly be a first — many other countries don't allow the patenting of genes at all. “It's illegal to do this in many other countries,” said Dr. Hoffman. “In Canada, for example, you can test all the breast cancer genes of all Canadians without any payment to Myriad.”
And in 2004, a European court limited Myriad's patent protections in the European Union. A charitable organization, Cancer Research, was granted the European patent on the BRCA2 gene; it allows free use of the patent by clinical pathology laboratories in Europe.
“Many other countries have worked around the US patent system when it comes to genes, because they felt it was unethical,” said Dr. Hoffman. “It's things like this, in many respects, that are driving US health care costs up as compared to other countries.”
UPCOMING AAN ANNUAL MEETINGS
• HONOLULU, HAWAII • APRIL 9-APRIL 16,2011
• NEW ORLEANS • APRIL 21-APRIL 28,2012