Legal battle over BRCA1 and BRCA2 patents continues

Myriad Genetics and ACLU both ask appeals judges to rehear case

Neither side in a lawsuit challenging gene patents is satisfied with a federal appeals court ruling that upholds Myriad Genetics' patents on the BRCA1 and BRCA2 genes.

Following the July 29 decision from the U.S. Court of Appeals for the Federal Circuit, both plaintiffs and defendants have petitioned the 3-judge panel to rehear the case, which many expect to go to the U.S. Supreme Court. That decision reversed a district ruling that invalidated gene patents, maintaining genes aren't patentable because they are products of nature. Plaintiffs include the American Civil Liberties Union, numerous medical associations including the American College of Medical Genetics, breast cancer patients, geneticists, and genetic counselors. They contend that exclusive patents on the BRCA1 and BRCA2 genes interfere with diagnostic testing, stifle research, and limit women's healthcare options because they can't get second opinions and must pay more than $3,000 for a test offered solely by Myriad Genetics.

Defendants include Myriad, the U.S. Patent Office, and the University of Utah Research Foundation, which is part owner of the patents. They maintain that isolating the genes from the genome constitutes a new product with medical use.

The appeals court's decision was neither a complete victory for Myriad nor a total loss for plaintiffs. The majority opinion states companies can obtain patents on human gene sequences because isolating and purifying a gene away from other DNA results in new chemical matter with medical utility, it also stated patents' claims on methods for comparing gene sequences are invalid.

The decision was not unanimous. Judge William C. Bryson's dissenting opinion rejected the notion that genes' isolation from the body warranted patenting. He likened this situation to “snapping a leaf from a tree.”

What Does It Mean?

While the appeals court's decision leaves Myriad's claims on specific BRCA mutations largely intact, “the scope and strength of patent protection are clearly less than before the case began,” Robert Cook-Deegan, MD, writes in the August 5 Cancer Letter (Cook-Deegan, 2011). Bryson's dissent leaves some room for a future decision that invalidates patents, says Dr. Cook-Deegan, who is Director of the Center of Genome Ethics, Law and Policy at the Duke University Institute for Genome Science and Policy. “Some kinds of DNA diagnostics are still under a shadow of uncertainty on how courts will interpret ‘isolated’ in the diagnostic context. That could be clarified upon further appeal, or it could remain muddy,” he writes in Cancer Letter.

In the short term, the appeals court decision has no substantial impact on genetic testing because it maintains the status quo, says James P. Evans, MD, PhD, Bryson Distinguished Professor of Genetics and Medicine, at the University of North Carolina at Chapel Hill and Chair of the now disbanded HHS Secretary's Advisory Committee on Society, Health, and Genetics (SACGHS), which recommended against gene patents. If patents are allowed to stand, “we must deal with the implications as whole genome sequencing becomes more common. No one knows how patents will affect use of genomic technology,” he says.

Differing Arguments

While the request for rehearing questions the appeals court's reasoning, Myriad's maintains that new circumstances warrant vacating the initial district court decision.

The plaintiffs say the appeals judges erred by concluding that the isolated DNA fragments claimed by the patents are markedly different from those that exist in nature. The petition also argues that the patents' language defines the function, not the structure, of the patented genes and fragments.

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The court ruled that companies can obtain patents on human gene sequences because isolating and purifying a gene away from other DNA results in new chemical matter with medical utility.

The Myriad petition for rehearing focuses on the right of plaintiff geneticist and pathologist Harry Ostrer, MD, to sue. He is the only individual plaintiff the appeals court said had the right to sue, maintaining that only he suffered direct harm from the Myriad patents because they prevented Dr. Ostrer from providing BRCA testing to patients although he was ready and able to do so. Myriad argues that Ostrer now lacks this legal standing because of his move from New York University (NYU) to Montifiore Hospital and the Albert Einstein School of Medicine, which has no dispute with the company over its BRCA patents.

What's Next?

Lawyers on both sides of the human gene patenting debate note that at this point several things could happen. First, the appeals court judges could rehear the case as both sides request. The other possibility is that all 16 judges in the federal circuit or the Supreme Court could be convinced to hear the case, explains Debra Lauren Greenfield, PhD, Adjunct Assistant Professor, UCLA Center for Society and Genetics, which has been working with the plaintiffs.

The biotech industry would welcome consideration by the entire federal circuit because its decision could help clarify issues for the Supreme Court, says patent lawyer and former molecular biologist Kevin Noonan, PhD, Partner at McDonald, Boehnen, Hullbert & Berghoff LLP in Chicago, Illinois.

Meanwhile, the Supreme Court has agreed to hear a case that could have a major impact in the suit against Myriad and the gene patents. In Mayo v. Prometheus, the high court will consider what constitutes a “natural phenomenon” and whether 2 laboratories run by Prometheus Laboratories in San Diego, California, have the right to claim that natural phenomena can be protected by patent. The central dispute is whether a test that measures patients' metabolite levels to determine drug dosage should be patentable.

Whole Genome Sequencing

Myriad's BRCA patents expire in 2014 and most existing human gene patents, covering roughly 20% of the genome, will expire by 2020, leading some to speculate that the debate over gene patents will dissipate in coming years. Dr. Evans says rancor over gene patenting will probably diminish in relation to isolated genes, but not the practice in general, especially once whole genome sequencing becomes common. “In whole genome sequencing, you could argue that one never isolates genes, so there's no patent infringement,” he says. He adds, however, that gene patents contain several different claims besides ones relating to isolated genes. Myriad, for example, currently claims the mental process of inspecting a DNA sequence, detecting a mutation, and deciding if there's an increased risk of breast cancer is patentable.

But Dr. Evans and the SACGHS refute such claims. In an April 2012 report to the Department of Health and Human Services they write that the U.S. patenting system's practice of assigning patents to single genes and the biotechnology industry's focus on exclusive licenses for genetic discoveries may hamper multiplex testing and, eventually, whole-genome sequencing.

Both the SACGHS report and the appeals court decision suggest a legislative rather than a legal solution to the debate over gene patents. But multiple federal bills banning gene patents, introduced by Rep. Xavier Becerra of California, have not advanced. The bills would ban patents on all products of nature, such as the human genome. In contrast, SACGHS's recommendation was more nuanced. It called for an exemption from liability for infringement of patent claims on genes to be included in tests used for patient care or medical research. “Ideally, there should be legislation that says you can't use gene patents for diagnostic purposes,” Dr. Evans says.

Drs. Evans and Noonan agree that Congress is unlikely to pass any gene patent legislation because Congress simply lacks the will to hash out the complicated issues involved. “Congress has enough trouble passing a budget resolution. Do you really think it can handle this?” Dr. Noonan asks.

While not an advocate of gene patents, Dr. Evans says they may be reasonable for development of drugs that cost hundreds of millions of dollars because the patents can attract necessary investors. Diagnostic tests can, by comparison, be cheaply developed, he notes, adding that not all patents are restrictive. For example, patents on the genes responsible for cystic fibrosis and Huntington disease allow dozens of labs to offer tests in a thriving marketplace. “In contrast, Myriad's patent locks the field down,” he says.

While Dr. Noonan says human gene patents are necessary to attract investment in medical advances, he adds that patient care would be just fine without them. “Arguments based on what makes money miss the point, which is: Do patents produce benefit for patients? They do not.”