Most geneticists agree: the US Supreme Court did an artful job of threading a complicated scientific needle with their decision in the case of Association for Molecular Pathology [AMP] v. Myriad Genetics, Inc., issued June 13. (All the more impressive considering that Justice Antonin Scalia confessed, in a qualification to his concurrence, that he was “unable to affirm…the fine details of molecular biology.”)
A unanimous Court held that naturally occurring DNA, as a product of nature, is not in itself patentable merely because it has been isolated; nor are DNA fragments like oligonucleotides. Complementary DNA (cDNA), by contrast, is patent eligible, the Court held.
Relying significantly on its longstanding decision in Diamond v. Chakrabarty — which ruled that genetically modified organisms can be patented — now more than three decades old, the Court declared that “Myriad did not create anything” with its discovery of the BRCA1 and BRCA2 genes. The decision, written by Justice Clarence Thomas, invalidated five of Myriad's patent claims on isolated DNA, but left intact what Myriad said were more than 500 “valid and enforceable” claims in 24 different patents.
“The Supreme Court did something very sensible,” said Robert Cook-Deegan, MD, research professor in genome ethics, law, and policy at the Duke Institute for Genome Sciences & Policy. “I think they were worried about two things: they didn't want to upset the apple cart for biotechnology, so they protected cDNA patents, which are the ones that are most valuable for biotherapeutics, while getting rid of patents on isolated DNA molecules.
“People like Harold Varmus and Francis Collins have argued that the way those claims were granted by the US Patent Office could have blocked anybody doing analysis of the whole genome, or any part of the genome that included chromosome 17 or 13. The molecule claims were so broad that they could have allowed Myriad to block anything they wanted to in the way of research or diagnostics, and while they didn't enforce those claims against basic research, they certainly did against clinical research.”
VICTORY FOR ALL SIDES?
All interested parties claimed some form of victory. “Bottom line, diagnostic genetic testing is now free from any patent threat, forever, and the poor can now have their genes tested as freely as the rich,” said Daniel Ravicher, executive director of the Public Patent Foundation, which with the American Civil Liberties Union had filed the suit against Myriad on behalf of AMP and other groups representing patients, scientists, and physicians.
Myriad, for its part, declared itself the victor as well. “We believe the Court appropriately upheld our claims on cDNA, and underscored the patent eligibility of our method claims, ensuring strong intellectual property protection for our BRAC analysis test moving forward,” said Peter D. Meldrum, the company's president and chief executive officer.
What this means for BRCA testing specifically is still unclear. Several labs have already announced that they will issue their own diagnostic tests; on the other hand, Myriad holds an enormous advantage over competitive diagnostic test manufacturers in the form of nearly a decade's worth of privately held patient data.
“I don't expect Myriad to do what they should, which is to share data publicly. In my view that's what they should have been doing all along,” said Dr. Cook-Deegan. “How does anybody know whether they're doing a good job of interpreting the clinical significance of the mutations they find? It's never been published and there's no independent verification of their calls.”
But he predicts that competitors will eventually catch up with Myriad on the data side as well.
More broadly, for the future of both genetic research (both in neuroscience and elsewhere) and biotechnology, several experts concurred with Dr. Cook-Deegan that the decision struck the right balance between protecting scientific investigation and protecting the interests of industry.
HOW IS NEUROLOGY AFFECTED?
“The decision gives investigators potentially more access to genetic information while still permitting industry to develop and market diagnostic tests and treatments,” said John Fink, MD, director of the neurogenetic disorders program at the University of Michigan's department of neurology.
Patent issues are more diffuse in neurology than oncology, Dr. Fink noted, because of the distribution of identified genetic risks over a wider set of genes. “In cancer genetics, a limited number of genes together represent a significant majority of cancer gene screening,” he said. “But in neurology there are many more genes involved, a much wider spectrum. I do think that the Supreme Court makes it more possible for investigators to develop diagnostic tests for ALS, for the ataxias, for dystonia, for muscular dystrophy, for hereditary spastic paraplegias.”
In 2010, Dr. Cook-Deegan published articles in a supplement to Genetics in Medicine assessing the impact of Athena Diagnostics' patents on genes and diagnostic tests for spinocerebellar ataxia and certain early-onset forms of Alzheimer's disease. Whether Athena's aggressive enforcement of the Alzheimer's disease patents affected clinical access was unclear, but in the case of spinocerebellar ataxia, Dr. Cook-Deegan said that patient and provider interviews showed a clear effect.
“Athena has enforced its exclusive rights to spinocerebellar ataxia-related patents by sending notification letters to multiple laboratories offering genetic testing for inherited neurological conditions, including spinocerebellar ataxia,” he wrote. About half of the responders to a web forum survey sponsored by the National Ataxia Foundation had decided not to get genetic tests. “Price was cited as an access concern by the physicians, and as sole US provider, coverage and reimbursement depend on having payment agreements between Athena and payers.”
Since the publication of Dr. Cook-Deegan's article, Athena has been acquired by Quest Diagnostics. “I think Quest is probably going to behave quite differently than Athena,” he said. “They're a huge diagnostic firm, and genetic testing is a very small fraction of their business. I would expect them to be interested in cultivating friendly relationships with payers and service providers. Myriad and Athena were really the only two companies that had this service monopoly business model, and I don't think they can rebuild that given the combination of the Myriad decision and the Mayo decision.” (Last year, in Prometheus v. Mayo, the court held that methods of administering drugs to treat a disease — in this case, gastrointestinal immune diseases — do not meet the patentable subject matter standard of section 101 of the Patent Act.)
Some investigators say that they now hesitate to seek patent protection for their own discoveries because of ethical concerns that have developed during the “gene patenting race.”
Louis Ptác???ek, MD, who leads the Division of Neurogenetics at the University of California, San Francisco, holds a patent on a screening method for a gene mutation associated with an increased risk of cardiac dysrhythmia, an inherited condition called Andersen Tawil Syndrome, which he discovered while at the University of Utah more than a decade ago.
“I would do that differently today,” he said. “My lab has probably cloned genes related to a greater number of disorders than anybody else in the world, and my own view is, why should we even begin to patent these genes or tests for rare neurogenetic syndromes? Especially for rarer disorders, today our inclination as investigators is not to even ask the university to pursue a patent. I want at-risk individuals to have access to the test if they want, at a reasonable price. To be holding patients hostage by charging exorbitant fees doesn't seem fair to me.”
But Dr. Ptác???ek draws a distinction between diagnostic testing and therapeutics. “There's a reason for wanting to be able to have patent protection in that arena,” he told Neurology Today. “If a pharmaceutical company takes a novel target discovered in my lab, and spends hundreds of millions of dollars finding lead compounds that are candidate drugs, chemically modifying them, and taking them to human trials, patent protection there is necessary. But the companies aren't paying for the discovery and cloning of the disease genes themselves: the NIH is, or HHMI [Howard Hughes Medical Institute], or Max Planck.”
“I have several gene patents, and the only reason I got them was to protect the situation we were in,” agrees Teepu Siddique, MD, Les Turner ALS Foundation/Herbert C. Wenske professor of the Davee department of neurology and clinical neurosciences at Northwestern University's Feinberg School of Medicine, whose pioneering work in amyotrophic lateral sclerosis has led to the identification of a genetic common cause in all forms of the disease. “And those patents were never really respected; companies like Athena have openly been advertising those genes and charging money. I think the Supreme Court's decision is wonderful; it creates a more level playing field for medicine.”
The Myriad decision is a win-win, Dr. Fink agreed. “It protects researchers‘ ability to pursue science, individuals’ ability to access diagnostic testing, and industry's financial incentives to embrace a research area.”