On June 13, the United States Supreme Court unanimously ruled that naturally occurring DNA cannot be subject to patent.
On June 13, the United States Supreme Court unanimously ruled that naturally occurring DNA cannot be subject to patent.1The landmark decision was the end of a 4-year court battle between the petitioners in the case, the Association for Molecular Pathology and the molecular genetic testing company Myriad Genetics Laboratories, Inc. For the past 17 years, Myriad Genetics was the sole laboratory offering clinical genetic testing for the breast- and ovarian cancer-predisposing BRCA1 and BRCA2 genes, having obtained several patents after discovering the location and sequence of these genes. The petitioners argued that genes are a product of nature and thus, patents held by Myriad Genetics on the BRCA1 and BRCA2 sequence were invalid. The Court agreed. Numerous professional organizations and advocacy groups praised the decision, claiming it would likely result in increased access to testing with reduced costs.2Researchers and laboratory directors predicted more open and unfettered access to genetic testing data that previously would have been considered proprietary, as well as use of new and improved methods of BRCA1/BRCA2 mutation detection. But what will be the impact on clinicians and their patients who are considering genetic testing, and on the biotechnology industry?
Without question, this ruling is a win for individuals with hereditary breast and ovarian cancer and their families. Within hours of the decision, 3 separate genetic testing laboratories announced that they would begin offering BRCA1 and BRCA2 genetic testing, all at significantly lower cost than previously available. With testing costs dropping, more insurers may be willing to cover the service, which will result in increased access to testing. Testing may also be more comprehensive and provide a more complete risk profile. Importantly, BRCA1 and BRCA2 can now be included in multi-gene panel testing, in which multiple genes known to contribute to a specific disease phenotype are tested at the same time. Panel testing for hereditary breast cancer has been problematic, because the Myriad patents prevented inclusion of the 2 genes most commonly responsible for the disease. As a result, women who qualified for screening were forced to have it done in step-wise fashion, with testing for BRCA1 and BRCA2 first, followed by additional panel testing only if BRCA1 and BRCA2 results were negative. The total cost of that approach is about $6,000. Since the Supreme Court ruling, 2 laboratories have already added BRCA1 and BRCA2 to their panels, offering testing for up to 25 genes at a cost equivalent to testing only for the 2 genes. More companies likely will follow.
For healthcare providers caring for patients at potential risk of cancer, the decision analysis surrounding molecular genetic testing now offers more options and greater flexibility. However, a free market also brings greater complexity. Providers ordering genetic testing now must be familiar with the various laboratories and the types of tests they offer and understand each test’s mutation detection rate, the quality and cost of the interpretation, and the options for insurance reimbursement. When considering a multi-gene panel for hereditary cancer conditions that includes BRCA1 and BRCA2, the provider will also need to consider and review with the patient other cancer syndromes that the testing may identify, such as Cowden or Li Fraumeni syndrome. Li Fraumeni syndrome is caused by heritable mutations in TP53 and includes family clustering of premenopausal breast cancer, sarcoma, osteosarcoma, and leukemia, as well as brain, adrenal ,and other cancers.3Cowden syndrome is a rare multiple hamartoma syndrome from mutations in PTEN associated with breast, endometrial, and thyroid cancer.4
The same principles apply to the many phenotypes that result from several genes, including some no longer subject to patent protection, such as the genes for Long QT syndrome. With larger gene panels, delivering effective pre- and post-test genetic counseling and accurately interpreting results are critical to ensure that patients make informed choices.
Although larger gene panels expand the scope of testing for the cancer phenotype of interest, many such panels include genes for which we have little clinical correlation. For most, there are no published practice guidelines to assist clinicians in acting on positive or negative results. For physicians already feeling the strain in today’s managed healthcare environment, staying current with best practices and spending additional time with patients to explain the purpose of larger panels before and after testing may be challenging. However, it is critical that the boon of increased access resulting from this ruling not be diminished by an increase in inappropriately ordered genetic testing or misinterpreted results.
Though the Supreme Court ruled that naturally occurring human DNA could not be patented, it did affirm that complementary DNA (cDNA) may be patented.2, 5, 6cDNA is artificially synthesized in the laboratory from naturally occurring genomic DNA. Many existing patents on human DNA sequences include claims on cDNA, and these patents will stand even after this ruling. The extent to which this will allow biotechnology companies to benefit from and protect their discoveries remains to be seen. For example, as a result of the Supreme Court ruling, 24 patents by Myriad containing more than 500 valid claims will remain in effect. The reaction to this seemingly ambiguous ruling within the biotechnology and patent law fields has been mixed. Some experts criticized the ruling as undermining the long-standing history of innovation and discovery, while others disagreed, saying that methods claims and use of modified DNA such as cDNA remain patent-eligible.2, 5, 6
Early signs indicate that the Supreme Court ruling in the Myriad case buttresses patient rights, increases access to genetic information, and enhances free market competition, which should reduce costs. We strongly support this ruling and these outcomes, even though we recognize that such a major decision may also adversely impact some of the many interested parties in unexpected ways. In the wake of this decision, at least for BRCA1 and BRCA2 testing in at-risk women, physicians and other healthcare providers will have more genetic testing options to assess risk of breast and ovarian cancer. Armed with up-to-date knowledge about cancer genetics, physicians and genetic counselors will have more tools to address their patients’ questions. That is progress!
1. The Supreme Court of the United States. ASSOCIATION FOR MOLECULAR PATHOLOGY ET AL. v. MYRIAD GENETICS, INC., ET AL. 2013. http://www.supremecourt.gov/opinions/12pdf/12-398_1b7d.pdf.
2. Perkel J. Gene patents decision: everybody wins. 2013. http://www.the-scientist.com/?articles.view/articleNo/36076/title/Gene-Patents-Decision--Everybody-Wins/
3. Schneider K, Zelley K, Nichols K, Garber J. Li-Fraumeni Syndrome. Gene Reviews 2013. http://www.ncbi.nlm.nih.gov/books/NBK1311/
4. Eng C. PTEN Hamartoma Tumor Syndrome (PHTS). Gene Reviews 2012. http://www.ncbi.nlm.nih.gov/books/NBK1488/
5. Liptak A. Justices, 9-0, bar patenting human genes. The New York Times. June 13, 2013. http://www.nytimes.com/2013/06/14/us/supreme-court-rules-human-genes-may-not-be-patented.html?_r=1&
6. Marshall E. Supreme Court rules out patents on ‘natural’ genes. Science. 2013;340:1387-1388.
Ms. Nagy is a genetic counselor in the Division of Human Genetics, The Ohio State University Wexner Medical Center, Columbus, and is the current president of the National Society of Genetic Counselors.
Dr. Rink is a clinical geneticist and holds an appointment in the Division of Molecular & Human Genetics, Nationwide Children's Hospital, Columbus, Ohio. She is also a maternal-fetal medicine specialist and the director of Genetics, Prenatal Diagnosis & Ultrasound in the Division of Maternal Fetal Medicine, The Ohio State University Wexner Medical Center, Columbus.
Dr. Hershberger is a cardiologist specializing in the genetic causes of cardiomyopathy and director of the Division of Human Genetics within the Department of Internal Medicine of The Ohio State University Wexner Medical Center, Columbus. His research is based at the Dorothy M. Davis Heart and Lung Research Institute at OSU.