Expressions follow SCOTUS gene ruling

Elizabeth Silverman

July 2013—The U.S. Supreme Court last month handed down a landmark decision on a narrow issue with broad implications for molecular medicine: Can genes be patented? In ruling that as products of nature, genes did not meet the criteria for patent eligibility, the Court brought its collective wisdom to bear on an issue that has troubled physicians, ethicists, and patients for nearly 20 years and hindered innovators in academia and industry. The Court declared invalid the patents on the genes BRCA1 and BRCA2, patents that were at the heart of an intellectual property estate that enabled Myriad Genetics to create a commercial monopoly in BRCA testing.

For all its apparent clarity, the full implications of the Court’s decision on BRCA1 and BRCA2 testing, and on products outside of genetic diagnostics, will probably not be known for some time. Also uncertain are Myriad’s intentions. Whether the company can or will use any of its remaining intellectual property to continue to try to block others from BRCA testing is an open question, particularly in light of its historically aggressive stand on patent enforcement. For now, those interested in offering genetic tests believe the Supreme Court’s decision has given them a powerful legal tool to do so, in BRCA1 and 2 testing and beyond. “The ruling gives pathologists freedom to operate in the genome,” says Debra Leonard, MD, PhD, professor and chair, Department of Pathology, University of Vermont College of Medicine and Fletcher Allen Health Care.

In the immediate aftermath of the Court’s decision, academic institutions such as the University of Washington and Montefiore Medical Center announced they would be offering BRCA1 and 2 testing. Commercial laboratories Ambry Genetics, GeneDx, Quest, DNA Traits, and Pathway Genomics followed suit. Ambry Genetics launched its test the day of the ruling and, says Ambry’s chief medical officer, Elizabeth Chao, MD, two independent legal teams concluded Ambry did have the freedom to operate. Ambry received four samples the day after it launched the test.

Although the Court’s decision was made on the narrow question of gene patents, the effects of its decision are expected to be far-reaching. Physicians will now have the same freedom of choice in diagnostic testing that has historically been the case with other diagnostic analytes, where patenting is an anomaly. Pathologists and lab directors are now free to bring testing in-house after evaluating technical proficiency, test volumes, and availability of specialized patient counseling. One who will undertake such analysis is Gregory Tsongalis, PhD, professor of pathology and director of molecular pathology, Dartmouth-Hitchcock Medical Center, who cautions: “These are complex tests and require careful counseling, and it may not be right for many labs to jump into it.”

Pathologists will also now be able to compare a number of outside commercial laboratories on quality, cost, time to result, and technology to make choices that are in the best interests of patients.

One thing they will not be doing: spending time huddled with legal teams trying to untangle what they can and cannot do in their laboratories. Margaret Gulley, MD, professor in the Department of Pathology and Laboratory Medicine, University of North Carolina, speaking in a CAP webinar in June after the Court decision, said: “Until last week a major consideration in whether to bring on a new test was not how much it would benefit our patients, but whether we would be likely to face a lawsuit for gene patent infringement. This decision opens the door for us to put patient needs first.”

Other effects of the ruling are wider access to second opinion testing and lower-cost tests. “Although mistakes are uncommon, some patients may still want a second opinion if they are considering surgery to make sure they are getting a correct result,” says Roger D. Klein, MD, JD, pathologist in the Department of Molecular Pathology, Cleveland Clinic. Arthur Caplan, PhD, professor and head of the Division of Bioethics at NYU Langone Medical Center, calling the Court’s ruling “correct,” says, “It will open up competition and enable second opinion tests.” Moreover, as long as Myriad remained the sole provider of tests with limited recourse to second opinions, there was no systematic way to evaluate the quality of its results. This situation is expected to change with the introduction in time of CAP proficiency tests. In fact, with respect to many aspects of BRCA1 and 2 testing—analyte patentability, freedom to offer in-house testing, ability to evaluate outside laboratories on measurable performance metrics, availability of second opinion testing, and ultimately proficiency testing—the Supreme Court decision appears to have normalized an aberrant situation in medical diagnostics and enabled it to be brought into line with current clinical standards.

Myriad currently charges $3,000 to $4,000 for its BRCAnalysis test—strikingly high compared with the dramatic decrease in the cost of gene sequencing over the past decade. For some women, the cost of BRCA testing created a barrier to care. The Supreme Court ruling “is a major step forward in providing patients with opportunities to have genetic tests done cheaper and available in panels of genes,” says Banu Arun, MD, professor of breast medical oncology and clinical cancer prevention, and co-director of clinical cancer genetics, The University of Texas MD Anderson Cancer Center.

Although many insurance carriers cover the cost of BRCA testing, “about 10 percent of our patients who need the test are uninsured,” Dr. Gulley says of the UNC. In addition, there are women whose insurance plans do not cover the test or for whom copays are prohibitive. Ambry quickly committed to a $2,200 price tag while DNA Traits announced testing for $995. Harry Ostrer, MD, professor of pathology, genetics, and pediatrics at Albert Einstein College of Medicine, says costs will come down because payers will pressure all labs. “Payment will be dictated by the new CPT codes that were implemented in January. Out-of-pocket expenses will be less for patients,” he says.

Mary-Claire King, PhD, professor of genome sciences and medicine at the University of Washington and discoverer of the BRCA1 gene, says, “There’s no question that not having testing available for all breast and ovarian cancer genes has cost lives. It’s an enormous relief that there will now be an open marketplace where a variety of approaches can be used.”