Cancer Gene Patents Upheld by Court -- At Least for Now

September 16, 2011 — Can human genes be patented?

Apparently so, at least for now. In July, a federal appeals court ruled on the issue and overturned a lower-court decision that invalidated 7 patents related to the BRCA1 and BRCA2 genes, which are markers of increased risk for breast and ovarian cancers.

The lawsuit was filed against the US Patent and Trademark Office and the owners of the patents — Myriad Genetics and the University of Utah Research Foundation.

There was a decidedly mixed reaction to the court decision, just as there are conflicting viewpoints regarding the whole issue of gene patents.

Critics argue that patenting human DNA is immoral and unethical, will inhibit 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.

To an extent, both sides might be right.

Two Sides of the Coin

Patents can both help and hinder, explained Robert Cook-Deegan, MD, director of the IGSP Center for Genome Ethics, Law & Policy at Duke University in Durham, North Carolina.

"Sometimes I do believe they help, by inducing investment in private research and development that makes things happen that would not happen at all, or not as fast if left to only public funding and nonprofit research," he told Medscape Medical News. "And sometimes they hurt, when used to hamper competition unduly — the whole idea is to constrain competition and have an incentive to invest in invention and to provide rewards for invention," Dr. Cook-Deegan added. "It's about balance, not absolutes, and yet the ways to measure innovation are weak, indirect, and often abused."

It really depends on how one manages the patent.

Another way of looking at the issue is that the patent itself is not the problem, it is the way it's exercised. "Patent holders make the decision about how to license the product, and it's the terms of the licenses that can be problematic," said Josephine Johnston, LLB, MBHL, research scholar and director of research operations at the Hastings Center, in Garrison, New York. "It really depends on how one manages the patent — that's what really matters."

"Myriad has held its patents very closely," she explained in an interview, "and has not licensed them out to other companies. They have had very tight control over how they managed the patents."

There isn't much in the way of case law to support the premise that patents that result from federal funding, such as in this case, must be exercised in a way that is in the public interest, Ms. Johnston said.
As an example, gene patenting occurs around the world, but many countries limit the scope of such patents to minimize any negative effect on healthcare costs and on the free flow of information in research.
Dr. Cook-Deegan agrees: "Often the question is not whether something should be patented, but how those patents are used, how broadly they should be interpreted, and how much activity they preclude."

Thus far, gene patents have proven useful in the development of some therapeutic proteins, he pointed out, but both the harms and benefits of DNA patents for clinical genetic testing remain unclear.

Patents can be important in developing therapeutics, he said, but added that they are not always necessary. "Some vaccines and penicillin were largely developed without patent incentives, but sometimes patents help, and sometimes even a lot."

Conversely, patents can stifle innovation by creating a monopoly that is hard to work around during the patent term, Dr. Cook-Deegan explained. "I think it's hard to argue that, in general, patents have hurt research, but I also think it's hard to argue that they've done much good, other than in therapeutics, vaccines, and other healthcare products, where the economic models that presume ample private research and development are fairly clear."

However, Wendy Chung, MD, PhD, director of clinical genetics at Columbia University in New York City, believes that the BRCA gene patents have stifled research and have had a negative effect on women's health.
"What is detrimental to the whole field, and for women especially, is that genetic testing for breast and ovarian cancer has stagnated for at least the past 10 years," said Dr. Chung, who is a coplaintiff in the lawsuit.

The community has been held hostage by having an exclusive provider.

"There haven't been market forces to push anyone to improve the testing," she explained in an interview.
"There have been scientific advances, but they haven't been realized in the clinical realm because there's no competition, there's no enforcing anyone to be better or pushing to improve the interpretation of these results, and no way of testing for other genes."

"I really feel like the community has been held hostage by having an exclusive provider," she added.

Patenting the Human Body

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

The first patent on a recombinant DNA method was granted more than 30 years ago, in 1980, after a US Supreme Court decision that a life form could 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 over gene patenting heightened when Myriad Genetics obtained patents on the BRCA1 and BRCA2 genes and refused to license the technology to other laboratories. Testing was kept inhouse, and Myriad was able to set a market price of about $3000 per test.

This lawsuit was not just about Myriad, but about gene patenting in general, explained Mark H. Stoler, MD, past president of the American Society for Clinical Pathology (ASCP), and a coplaintiff in the lawsuit.
Myriad, however, is an example that everyone can relate to, he said in an interview. "The BRCA1 and BRCA2 genes are important in breast cancer, and the number 1 example."

The ASCP joined the lawsuit for 3 basic reasons — quality, cost, and, most important, 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.

For example, the lab might not accept the patient's insurance or what the insurer will pay. There are a variety of ways in which sole-source laboratories that do not license broadly can present barriers to patient access.
Another reflection of limited access is the need for a second opinion. "How can you get a second opinion if there is only 1 lab running the test?" he asked, adding that some patients have resorted to sending samples to countries that do not honor American patents.

"That brings us to the issue of quality," Dr. Stoler pointed out. "There is no way to measure quality if you can't do comparison testing."

Many of the usual mechanisms of sharing data, comparing results, and assessing variation aming laboratories is problematic if there's only 1 laboratory, he added.

Finally, although not nearly as important as access and quality, is cost. "If you're the sole-source vendor, you set the price and people pay the price or they don't pay the price," said Dr. Stoler. "There's no competition or price controls."

He noted that prices can theoretically change over time, "but the cost of BRCA testing has not gone down despite advances in the technology underlying the basic testing process."

Ruling Overturned

On May 12, 2009, the American Civil Liberties Union and the Public Patent Foundation filed a lawsuit charging that patents on human genes violate the First Amendment and patent law because genes are "products of nature," and therefore can't be patented. Coplaintiffs in the case were several medical organizations, physicians, academic researchers, and patient advocates.

In March 2010, a New York federal court ruled that the patents on the BRCA1 and BRCA2 genes were invalid; Myriad appealed this case. The US Court of Appeals for the Federal Circuit subsequently declared that, under Section 101 of the United States Patent Act, the composition of matter claim covers the isolated DNA and complementary (c)DNA of the BRCA1 and BRCA2 genes.

As expected, Myriad was pleased with the ruling. "We strongly support the Court's decision that isolated DNA and cDNA are patent-eligible material, as both are new chemical matter with important utilities [that] can only exist as the product of human ingenuity," said Peter Meldrum, president and CEO of Myriad Genetics, in a statement.

"Furthermore, we believe this decision is in the best interests of the agriculture, biotechnology, and pharmaceutical industries, as well as the hundreds of millions of people whose lives are bettered by the products these industries develop based on the promise of strong patent protection," he added.

Not Quite Resolved

Despite the court ruling, this is not an issue that is going to be resolved any time soon.
"The DNA sequence is a thing of nature and not a patented unique process," said Dr. Stoler. "Based on that principle, we hold that gene patients should be invalidated, even though they have been widely granted by the
US patent office."

It has been speculated that the case will move up to the Supreme Court, and "that if it goes to the Supreme Court, it will be accepted by the Court," he noted.

The case has gone as far as it can through the lower courts. "The New York court accepted the principles that we were arguing for, but the next-level court has a history of favoring corporate patent holders," said Dr. Stoler. "It favored Myriad to some degree, although not completely. Now both sides are appealing and trying to get that decision re-evaluated. How it is presented to the Supreme Court for consideration will have to be determined."

One direction might lie with the federal and state governments, rather than with the court. In fact, Dr. Chung feels that this might have had an impact on the most recent ruling.

"In my opinion, the judges would prefer that this was settled by the legislative branch," said Dr. Chung.

"There is a long history of the patent office issuing patents for genes. I think that the judges were concerned about overturning a very long precedent in terms of the foundation for the biotech industry," she told
Medscape Medical News. "And I think they're afraid that a sweeping judgment might have an irreparable effect in the biotech industry. So rather than having it decided by the judicial system, it is preferable to have the legislative branch decide this by basically legislating it one way or the other."

"My sense...is that that was what their concern was," she added.

In 2007, Rep. Xavier Becerra (D-California) introduced the Genomic Research and Accessibility Act (GRAA), which would prospectively bar the patenting of any "nucleotide sequence, or its functions or correlations, or the naturally occurring products it specifies." The bill has not moved forward since its introduction.

Whether or not the case moves to the Supreme Court or laws are passed regulating the patenting of genes, rapidly advancing technology might make these points moot.

"As we start genetic evaluation in a comprehensive way for all genes, it becomes rather ridiculous to think that people are going to be able to find out about gene X but not gene Z because someone holds the intellectual property for it," Dr. Chung pointed out. "Right now this is an issue for BRCA, but there are hundreds of genes that this will apply to."
Cancer Gene Patents Upheld by Court -- At Least for Now