What's Yours is Mine: The Continuing Controversy over Gene Patenting

Pigs may have been flying in March of 2010, but they seem to have landed with a resounding thud late this summer.

On Friday, July 29, 2011, the Federal Circuit Court decided the “ACLU/Myriad” gene patenting case, formally known as Assn. Molec. Path. et al. v. USPTO et al. In a majority opinion by Judge Lourie, the court addressed the case on the merits, after finding that at least one plaintiff (Dr. Harry Ostrer) had standing to sue. The court held all “isolated DNA” claims at issue patent-eligible, but held as patent-ineligible diagnostic method claims that in effect recited only “comparing” or “analyzing” DNA sequences.

In layman’s terms, this means that companies can obtain patents on the genes but cannot patent methods to compare those gene sequences. The decision allows companies like Myriad Genetics, which controls the patents on the BRCA1 and BRCA2 genes, to exclude others from testing and conducting research on patented genes. Patients who want to obtain genetic testing to determine whether they are at risk for hereditary breast and ovarian cancer have only one option for full genetic sequencing: Myriad Genetics. Myriad decides what tests are offered, which mutations are included, at what cost, and what research can be conducted without fear of patent infringement liability.

“This ruling is a blow to the idea that patent law cannot impede the free flow of ideas in scientific research,” said Chris Hansen, a staff attorney with the ACLU Speech, Privacy and Technology Project. “Human DNA is not a manufactured invention, but a natural entity like air or water. To claim ownership of genetic information is to unnecessarily block the free exchange of ideas.”

In a prepared statement, Myriad President and CEO Peter Meldrum said: "We strongly support the court's decision that isolated DNA and cDNA are patent-eligible material. ...We believe this decision is in the best interests of the agriculture, biotechnology and pharmaceutical industries." Myriad noted that the court had rejected five of the six Myriad methods claims in dispute, but pointed out that 237 other methods claims for its cancer risk test, BRACAnalysis, were not affected.

In what many considered an interesting twist, the Federal Circuit denied both the ACLU's petition for rehearing (September 13, 2011) and Myriad’s (September 16, 2011) as well. Both parties now have 90 days to file a certiorari petition (a writ or order by which a higher court reviews a decision of a lower court) asking for a Supreme Court review.

At its essence, the Federal Circuit’s 2-1 decision returned the law to the state it was in before District Judge R. Sweet’s opinion turned things topsy-turvy in March of 2010. Judge Sweet ruled that the BRCA gene mutations linked to breast and ovarian cancers do not differ from genes found in nature, and thus were not innovations. Since ‘products of nature’ cannot be patented, his verdict undermined the fundamental basis on which companies file patents: that the act of isolating and purifying the genes makes them different from what is found in nature.

The Federal Circuit court’s three lengthy opinions (a total of 105 pages) appear to invite higher authorities (the Supreme Court and the Congress) to ultimately step in at some point down the road.

There was partial dissent, with one of the judges on the panel writing that patents on the genes should be invalid. Judge William C. Bryson feels that “Extracting a gene is akin to snapping a leaf from a tree. Like a gene, a leaf has a natural starting and stopping point. It buds during spring from the same place that it breaks off and falls during autumn. Yet prematurely plucking the leaf would not turn it into a human-made invention.”

Unlike Judge Sweet’s district court decision in 2010, this Federal Circuit decision is precedential and binding on courts until or unless the Federal Circuit says otherwise, or the Supreme Court steps in. To date, no one knows exactly if or when the Supreme Court might take the case, and what Justices will say if they do.

Looking Back …

The case was originally filed by the ACLU and the New York-based Public Patent Foundation on behalf of doctors, patients and several medical groups, including the Association for Molecular Pathology and the American College of Medical Genetics.

The original ruling against Myriad in March of 2010 was quite a surprise to many in the legal and business community, since they had been basing tens of millions of dollars' worth of business on the ability to patent genes as far back as the 1980s.

The genes for both BRCA1 and BRCA2 were first patented by geneticist and Myriad founder Mark Skolnick, who in the 1990s began looking at detailed family histories to zero in on the genetic basis for breast cancer. Family histories helped him figure out which genes probably carried the mutations. Using gene sequencing, he found exactly where on the genes the mutations occur.

In the ruling, U.S. District Court Judge Robert Sweet in New York State invalidated part of seven patents granted to Myriad on the BRCA1 and BRCA2 genes. In doing so, he might have changed the face of genomic medicine. Might have. These recent rulings once again leave this very much in limbo.

After the original ruling, Hank Greely, a law professor at Stanford University and expert on biotech law called Sweet's ruling "surprising." According to Greely, the legality of whether or not genes are patentable had been left open over the last 30 years because the original decisions to allow such patents weren't all that clear. It was assumed and everyone thought they would stand since the patent office had been granting and courts had been upholding them for all that time. A further consideration is the tens of millions of dollars invested. Instead, Sweet in his ruling in effect said, You didn't invent this, you didn't make it, you shouldn't get a patent on it.

The ACLU believes the proper time for a patent does not come when a company has isolated a gene, but when it has developed a drug or test based on that gene. "That's what actually happens in much of biotech, they're actually patenting things they're creating," says Sandra Park, one of the lawyers who argued the case.

Myriad, on the other hand, argues that gene patents offer companies the time to develop those drugs and tests.

The U.S. Patent and Trademark Office (PTO) has granted thousands of patents on human genes – in fact, about 20 percent of our genes are patented. A gene patent holder has the right to prevent anyone from studying, testing or even looking at a gene. As a result, scientific research and genetic testing has been delayed, limited or even shut down due to concerns about gene patents.

Several major organizations, including the American Medical Association, the March of Dimes and the American Society for Human Genetics, filed friend-of-the-court briefs in support of the challenge to the patents on the BRCA genes. In addition, the United States Department of Justice filed a brief arguing that many of the gene patents issued by the Patent Office are invalid.

Listening to the voice(s) of reason…

The plaintiffs in the ACLU/Myriad gene patenting case present a mixture of voices both large and small. The real issue here is simple. Are cures about profits or people? Here is what some of the plaintiffs have to say about why they got (and remain) involved:

The American College of Medical Genetics maintains that genes and their mutations are naturally occurring substances that should not be patented. With breast cancer affecting an estimated one in eight women, ACMG has grave concerns over the human cost of patents on genes such as BRCA1 and BRCA2 that are important in the diagnosis, management and risk assessment of this and other serious human diseases. For example, patents on the BRCA1 and BRCA2 genes may prevent a woman considering a radical surgical procedure from obtaining a second opinion or confirmatory test. In addition, when genes are held as monopolies, and few or no other labs are allowed to perform the diagnostic tests, there is no incentive for quality assurance or improvement of the tests.

The Association for Molecular Pathology believes gene patents can serve as a disincentive to innovation in molecular testing because they deny access to a vital baseline of genomic information that cannot be "invented around." Moreover, threat of enforcement from a patent holder and ensuing litigation costs lead to a chilling effect as clinical laboratories and manufacturers are reluctant to develop new tests that could directly benefit patients. Regardless of the outcome, this case has potential to significantly clarify the extent of protection provided by gene patents. AMP also believes that this case is consistent with its role in public policy and the need to take principled stands on issues that impact the molecular pathology profession and the patients we serve.

The American Society for Clinical Pathology feels gene patents limit the broad availability of diagnostic tests due to the simple fact that laboratory scientists are prohibited from performing genetic tests because of patent enforcement and the threat of litigation. As a result, the market is dominated by a single provider, eliminating competition and scientific diversity, which ultimately drives up costs. Gene patents potentially infringe on patients' rights, denying them access to their own genetic information. Such patents stifle the innovative process, negating further refinement in test methodology, improvements in quality, and access to testing for the uninsured as well as those whose health care coverage requires that testing be reimbursed by a third-party payer.

Breast Cancer Action finds it highly problematic that, because of Myriad's patents, their BRCA test results cannot be verified by any other lab. This means that patients may be getting false negatives and false positives and have no way of knowing it. They are also very troubled that Myriad's patents interfere with research needed to gain a better understanding of certain genetic mutations that may or may not be associated with breast cancer. Ethnic minorities, including African-Americans, Hispanics and Asian-Americans, are disproportionately likely to receive ambiguous test results. Finally, they object to the fact that Myriad is able to charge a high price for its test because their patents on the genes allow them to bar competition. Women who do not have insurance, or whose insurance companies refuse to cover the test, have no access to this testing.

Arupa Ganguly, PhD says, “In 1995, I joined the department of Genetics at the University of Pennsylvania, as the then co-director of the Genetic Diagnostic Laboratory (GDL). I joined this lawsuit because I am concerned that gene patents have a chilling effect on scientific research.

Right now, any researcher who wants to study a patented gene must obtain permission from the patent holder, and the patent holder has the right to – and often does – prevent them from using or even looking at that gene. Unfortunately, the proliferation of gene patenting has limited the ability of many researchers to set up important tests. I and my fellow researchers are forced to constantly worry about violating patents, and as a result there are things we completely avoid. This ultimately takes its toll on the patients – the very people gene patent holders claim they are trying to help. I became a scientist because of the endless possibilities for discovery and progress in my field, but now so much research is blocked by the legalities of patents. That seems to me to go against the spirit of my work.”

Kathleen Raker is definitely in the trenches … “I'm a 41-year-old mother of two and live with my family in North Central Pennsylvania. Both my mother and maternal grandmother died from breast cancer. I'm worried about having a genetic predisposition for cancer, but haven't been able to afford an additional test that would give me information about my genes. I'm joining this lawsuit because I believe that gene patents should not prevent access to testing to people who find themselves in situations like mine.

"I got BRCA testing from Myriad in 2007, and it was negative. But I found out that there was additional testing that would look for other genetic links to cancer on the BRCA genes that were not covered by the test I received. I was upset to learn that this additional testing was offered separately, at an extra cost, and that I would probably need to pay up front. I haven't gotten this additional testing because I can't afford it.”

Vicky Thomason is another breast cancer survivor seeking change … “I live in Kentucky and work as a midwife for horses. I'm in my early '50's and was diagnosed with ovarian cancer three years ago. I joined this lawsuit because I do not think one company should control genes that are linked to breast and ovarian cancer.

After I was diagnosed with ovarian cancer, my doctor recommended that I get BRCA genetic testing to see if I was also at a higher risk for breast cancer because there is a history of it in my family. When my test results came back, they were negative, but my doctor told me that I needed an additional test offered by Myriad - not included in its original test package – to be able to get a more complete answer. The additional test looks for other mutations that are associated with cancer.

The problem is that the additional test costs more than I can afford. I don't get paid a big salary and neither does my husband who is disabled. It's been almost two years since the extra test was recommended but I still can't afford it. I get up every day not knowing if I have a mutation.”

Looking forward

It will probably be years before this case is finally settled, but the irony may be that by the time it is, the driving issue will be a moot point. An April 2010 article at Forbes.com noted that new technology may soon make Myriad’s gene test obsolete. New high-speed, high throughput gene sequencers from companies such as Illumina and Life Technologies will soon be able to sequence billions [of base pairs] for the price Myriad is charging for its BRCA test. The Forbes reporter went on to write that, although the court battle over gene patenting is hardly over, the one-gene-one-disease business model is “marked for dead.”

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 co-plaintiff in the lawsuit.

"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.

"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."