For the second time, the US Supreme Court has agreed to hear a lawsuit that challenges patents on the BRCA1 and BRCA2 genes, which identify a higher risk for breast and some other cancers.

The court will attempt to answer an elusive and contentious patent-law question: Can a human gene can be patented? Central to the argument is whether isolated DNA is a product of nature, and therefore ineligible for patent protection.

"This is an issue that is vitally important to breast cancer; in fact, it reaches far beyond breast cancer," said Karuna Jagger, executive director of Breast Cancer Action, a not-for-profit national organization. "Patenting human genes has broad implications. In this case, we're not talking about a particular technology or methodology, we're talking about a patent on the actual BRCA1 and BRCA2 genes themselves," she explained.

This hearing will be the end of a long and protracted case. Myriad Genetics acquired patents on the 2 genes in the mid-1990s. Since that time, it has become the sole commercial provider of testing services for BRCA1/2 in the United States.

This was a public investment, and then it was privatized by Myriad.

The BRCA1 gene was first mapped and identified in 1990 by Mary-Claire King, PhD. At the time, she was working at the University of California at Berkeley, and her research was primarily funded with federal dollars. "This was a public investment, and then it was privatized by Myriad.... And Myriad's monopoly has created barriers," Jagger told Medscape Medical News.

Some experts have suggested that the upcoming case is moot, because Myriad's patents will expire in 2015. But Jagger noted that there are many ways for patents to be extended, and that this case will undoubtedly set a precedent for future attempts at gene patenting.

BRCA1 and BRCA2 are not the first genes to be patented. In the United States, 3000 to 5000 patents have been issued on human genes, and 47,000 patents have been issued for inventions involving genetic material. In fact, more than 20% of the human genome has been patented.

The first patent on a recombinant DNA method was granted in 1980 after the US Supreme Court ruled that lifeforms could, indeed, be patented. This led to a subsequent trend by the US Patent and Trademark Office to award patents to isolated disease-specific segments of DNA that could be used for diagnostic and therapeutic purposes.

The controversy brewing around gene patenting reached a climax when Myriad refused to license the technology to other laboratories. Because testing remained in house, Myriad was able to set a market price of about $3000 per test.

A Lengthy Process

On May 12, 2009, the American Civil Liberties Union (ACLU) and the Public Patent Foundation filed a lawsuit against the US Patent and Trademark Office, Myriad Genetics, and the University of Utah Research Foundation, which hold the patents on the BRCA1 and BRCA2 genes. It charged that patents on human genes violate the First Amendment and patent law because genes are "products of nature," and therefore cannot be patented.

Coplaintiffs in the case, including several medical organizations, physicians, academic researchers, cancer survivors, and patient advocates, represented 150,000 geneticists, pathologists, and laboratory professionals.

The case has taken a long and convoluted route through the court system. On March 29, 2010, a New York federal court ruled against Myriad, finding that patents on the BRCA1 and BRCA2 genes were invalid. It was the first time a US court had invalidated a gene patent.

Myriad appealed the case, and it was heard by the US Court of Appeals for the Federal Circuit in April 2011. Three months later, the appeals court ruled in Myriad's favor, finding that companies can obtain patents on specific genes.

In March 2012, the US Supreme Court instructed the appeals court to reconsider the case after a unanimous ruling that invalidated 2 patents on a blood test that determines drug dosages, which had been licensed to Prometheus Laboratories.

In August 2012, a divided federal appeals court (2 to 1) ruled in favor of Myriad and gene patents in general. However, the court invalidated patents on methods used to compare gene sequences. A month later, the plaintiffs once again asked the Supreme Court to hear the challenge to Myriad's patents. In November 2012, the Supreme Court agreed to hear it during the current session.

Contention and Controversy

The very idea of patenting genes has been a subject of contention and controversy. Critics argue that patenting human DNA is immoral, unethical, inhibits medical research and, most important, can negatively affect patient care. Proponents argue that patents are necessary to promote innovation, research, and the large capital investments necessary for the development of drugs and diagnostic tools.

Mark H. Stoler, MD, past president of the American Society for Clinical Pathology (ASCP), and a coplaintiff in the lawsuit, noted that the ASCP joined the lawsuit for 3 basic reasons: quality, cost, and access.

"When a laboratory has exclusive rights to test for a gene, as is the case with BRCA1 and BRCA2, and that test might be used to help patients with a genetic abnormality, access can be limited," said Dr. Stoler, professor of pathology, cytology, and gynecology at the University of Virginia School of Medicine in Charlottesville, in a previous interview with Medscape Medical News.

There are a variety of ways in which sole-source laboratories that do not license broadly can create barriers to patient access. For example, a laboratory might not accept the patient's insurance or what the insurer will pay.

However, according to Myriad, approximately 95% of all appropriate patients have access to breast cancer susceptibility tests through private insurance, Medicare, Medicaid, or the Myriad Financial Assistance Program. "Under our Financial Assistance Program, we test low-income, uninsured patients at no charge, and have provided free testing to more than 5000 patients just in the past 3 years," the company reports.

Another issue that has been raised is that it is impossible to get a second opinion because of Myriad's exclusivity. "Women may want a second opinion on their test results," said Jagger.

Myriad refutes this, pointing out that since 1999, many laboratories have been performing second-opinion testing, including the UCLA Diagnostic Molecular Pathology Laboratory; the University of Pittsburgh Medical Center; the University of Chicago Genetic Services Laboratory; the University of California San Francisco Molecular Diagnostic Laboratory; the Fox Chase Cancer Center; and the University of North Carolina Hospitals.

But Is it Patentable?

The Supreme Court has not accepted all parts of the case, explained John M. Conley, JD, PhD, professor of law at the University of North Carolina School of Law in Chapel Hill. "They are only addressing...patents on the genes themselves, as opposed to patents on methods that interpret gene mutations. They are only going to focus on the issue of whether genes are patentable," he told Medscape Medical News.

The Myriad patents have 2 product subcategories. "We are going to get a ruling on whether genes in isolation are patentable, and we will also get a ruling on whether cDNA is patentable," he explained.

Dr. Conley pointed out that "many in the scientific community say that these single-gene patents are not as important as they used to be because the sequencing technology has moved away from using single genes in isolation."

However, patents can affect technology that focuses on large panels of genes. In such cases, "researchers would have to find everyone who has a patent on the genes," said Dr. Conley. "And then what do they do? Try to get individual licenses? Ignore the patent? Companies that do this kind of work worry about the patents, and they would be very happy with a ruling against Myriad."

It is possible that a ruling against Myriad would be retroactive, he added. "All patents on individual genes and isolated genomic DNA could be wiped out, depending on the ruling. That would be very welcome for companies in the personalized medicine business."

Dr. Conley added that the fundamental core question being presented to the court is whether "these are the kinds of things that can be patented under section 101 of the Patent Act."

High Stakes

Many scientists and physicians believe that this type of patent is detrimental to patient care and research. "If overruled, we will see a spark of innovation, more accurate tests that are lower cost, and more research," Jagger predicted. "The stakes are high for breast cancer, but also across healthcare. These issues are the same across other types of cancer and diseases."

This is the end of the line for this particular case.

At this point, it is all speculation. "We don't know how they will rule," said Chris Hansen, a staff attorney at the ACLU. "They have agreed to hear the case, so at least that means it is still alive.... But this is the end of the line for this particular case," he noted.

"Of course, we are hoping that they invalidate the patents," Hansen added.