Breast and Ovarian Cancer Testing After the Myriad Genetics Decision

Rosemary Frei, MSc

June 2010, Vol 1, No 2 - Genetic Testing


There’s no question that when, on March 29, a federal district court judge ruled the patents held by Myriad Genetics to the BRCA1 and 2 gene mutation sequences are invalid, a shock went through the healthcare and genetics communities.

What’s also not in doubt is that the case will continue—Myriad immediately indicated it will appeal the decision to the Court of Appeals for the Federal Circuit, which has been the appeal court for all patent cases since 1982.

What remains an open question, however, is whether the court will uphold this first ruling—and, if it does, whether and to what extent the justices of the Supreme Court will do the same.

“There was a lot of hand-wringing before the ruling that if the case went the way the ACLU [American Civil Liberties Union] wanted it to, biotech would be dead,” observed Robert Cook-Deegan, MD, director of theInstitute for Genome Sciences & Policy’s Center for Genome Ethics, Law & Policy at Duke University in Durham, NC. “That of course is garbage. It’s very unlikely that courts are going to invalidate all gene patents retroactively.”

Value-Based Cancer Care has waded into the fray to understand Judge Robert W. Sweet’s decision, and how Myriad and its tests may fare in the court and the marketplace.

The Judgment 

The ACLU Foundation and the Public Patent Foundation, together with the Association for Molecular Pathology (AMP), filed a lawsuit on May 12, 2009, in the US District Court for the Southern District of New York against the United States Patent and Trade mark Office (USPTO) and Myriad Genetics and the University of Utah Research Office. The latter 2 organizations hold 7 patents relating to the BRCA genes, and the ACLU Foundation and the AMP were plaintiffs together with other groups such as the American Society of Human Genetics and the American College of Medical Genetics.

The lawsuit contended that the BRCA1 and 2 DNA sequences are products of nature and hence cannot be patented. The plaintiffs asked for a summary judgment from Judge Sweet; in other words, they asked that there not be a trial by jury but rather that the judge make his own decision. This was because they believed that it was the interpretation of the facts rather than the facts themselves that were contended by themselves and the defense.

In his March 29, 2010, decision, Judge Sweet agreed to provide a summary judgment.

In his judgment, Judge Sweet did not weigh in on the plaintiffs’ contentions that patenting gene-based material is unconstitutional, and that patents stifle research and impede patient access to testing and treatment.

He agreed with the plaintiffs, however, that the BRCA1 and 2 gene sequences are not markedly different from wild-type or native DNA and hence cannot be patented. He also agreed that Myriad’s patents for its methods of isolating, sequencing, and comparing DNA segments from patients to those with BRCA1 and 2 mutations are invalid. His reasoning was that the isolated segments are products of nature that don’t have significantly different characteristics from those in their native state, and that isolating and sequencing segments is a set of simple data-gathering steps that do not involve any new technologies or processes.

Thus the judge concludes that “the patents issued by USPTO are directed to a law of nature and were therefore improperly granted.”

The Reactions

The day after Judge Sweet made his ruling, the next phase of the battle began.

In a news release indicating Myriad will appeal the decision, the company’s president and CEO struck back.

“While we are disappointed that Judge Sweet did not follow prior judicial precedent or Congress’s intent that the Patent Act be broadly construed and applied, we are very confident that the Court of Appeals for the Federal Circuit will reverse this decision and uphold the patent claims being challenged in this litigation,” said Peter Meldrum. “More importantly, we do not believe that the final outcome of this litigation will have a material impact on Myriad’s operations due to the patent protection afforded Myriad by its remaining patents.”

BIO—the Biotechnology Industry Organization—also released a statement that day defending Myriad. BIO is one of the groups that had filed briefs before Judge Sweet in support of Myriad Genetics and the USPTO.

“The invalidation of the diagnostic method claims was done under a Federal Circuit opinion…which will soon be clarified further by the Supreme Court,” BIO president and CEO Jim Greenwood said in the statement. “From the mass production of life-saving medicines by cell cultures to the screening of our blood supply for life-threatening viruses, patented DNA molecules have been put to countless uses that have benefited society. Preparations of isolated and purified DNA molecules, which alone can be put to use in these ways, are patentable because they are fundamentally different from anything that occurs in nature.”

For their part, the AMP cheered the judgment. A release sent to the media on March 31 used unequivocal language.

“This is a landmark decision that has the potential to dramatically improve patient access to genetic testing. It is a boon to personalized medicine in the purest sense, as nothing is more personal than one’s genetic makeup,” AMP president Karen Mann, PhD, said in the release. “…DNA patents have delayed, limited, or even shut down clinical testing and scientific research, and in the case of BRCA genes, Myriad’s lab is the only place in the country that performs full sequencing of the genes for diagnostic purposes. Patients can’t get a second opinion before they make major, irreversible health decisions.”

When asked by Value-Based Cancer Care to further clarify this statement, Dr Mann opined that bringing more competition into BRCA testing would broaden access and potentially improve accuracy.

“We’re not claiming that Myriad is doing bad testing. But if you have more people [and laboratories] doing the same test with different methods, that can help resolve indeterminant results. And also, if there were multiple people offering the test, I have no doubt it would be cheaper.”

The Context

Two sets of case studies that happened to be published just 2 weeks after Judge Sweet made his ruling provide a wealth of material on whether gene patents and licensing practices hinder access to genetic testing for cancer. Both papers took years to complete, and both were published in the journal Genetics in Medicine.

In one of the analyses, E. Richard Gold, BSc, and Julia Carbone, LLB, outline the formation of Myriad Genetics in 1991 by University of Utah researcher Marc Skolnick, and how the tension built up between Myriad and the clinical research community, the public, and healthcare administrators.1

After Myriad secured patents that covered the entire BRCA1 gene and the tools to sequence and compare patients’ gene sequences, it introduced a test for BRCA1 and 2 in the late 1990s. It has the exclusive license to use these tests in the United States.

Shortly thereafter, Myriad sought to ensure the exclusivity of testing by issuing cease-and-desist letters to the Genetics and IVF Institute (GIVF) and the University of Pennsylvania’s Genetic Diagnostic Laboratory (GDL) in 1998. GIVF immediately stopped BRCA testing, but GDL did so only after Myriad signed an agreement with the National Cancer Institute (NCI) that stipulates the company has to provide, at cost or below cost, testing to the NCI and any researcher working on an NCI-funded project.

The fact that Myriad was willing to quickly jump into the enforcement track against any group performing testing created enmity not only within the research community, but also, eventually, with patients and large swaths of the healthcare sector.

Indeed, the Secretary’s Advisory Committee on Genetics, Health, and Society, which advises the Secretary of Health and Human Services on a range of issues relating to the intersection between genetics and medicine, issued a report on February 10, 2010, that determined gene patents are not an important incentive to develop and make available genetic tests. The committee recommended, among other things, that any group or individual with the appropriate equipment and expertise should be able to conduct diagnostic testing, even if there are patents covering parts of that testing. This was part of the crack in the gene-patenting superstructure that may well have helped lead to Judge Sweet’s decision.

Gold and Carbone in fact make a convincing case that it was because of Myriad’s aggressive and nonconciliatory practices that the company and indeed the whole biotechnology community have found themselves de fending the very right to patent genetic sequences.

Dr Cook-Deegan is the first author of a paper in the same issue of Genetics in Medicine comparing the impact of gene patents and licensing practices in breast, ovarian, and colon cancers.2 He told Value-Based Cancer Care that in the diagnostics fieldsthere are few companies like Myriad with exclusive patent rights, and that use their exclusivity and patent protection to reduce competition only after other companies’ products have reached the market first.

“This is very unusual—that wouldn’t be the case for Lipitor or other drugs, or even for gene-based biologics like erythropoietin,” he said.

In their analysis—in which Dr Cook-Deegan and his team compare the development of, and access to, testing for BRCA1 and 2 to that for hereditary non-polyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP)—they find that the price Myriad charges for analyzing a small unit of DNA known as an amplicon is lower for BRCA1/2 than for the colorectal-cancer genes.

Myriad charges $38.05/BRCA1 and 2 amplicon, compared to $40.80/FAP amplicon and $49.17/HNPCC amplicon. Its FAP price is at the high end of what other groups charge, and its HNPCC price is in the middle of the range, Dr Cook-Deegan and his coinvestigators found. The patents for the genes associated with HNPCC are held by the Oregon Health Sciences University and the Dana-Farber Cancer Institute in Seattle, and Johns Hopkins University. The patent for the FAP-associated gene is held by Johns Hopkins. The licenses for testing for the genes are held by 7 academic institutions and by Myriad and Quest Diagnostics.

Additional findings from the team include:

  • Despite the company’s maintaining it has never enforced its patents on the BRCA1 and 2 genes and tests for them against basic-science researchers, “Myriad cannot fully elude responsibility for any chilling effect on research, because the company could fully anticipate that others would refrain from research for fear of being sued for infringement,” in light of Myriad’s earlier actions against GIVF and GDL;
  • Myriad has only developed bloodbased testing and has decided not to test paraffin-embedded tissue even though there are instances in which the latter might be clinically useful; in contrast, in the area of colorectal-cancer forms of testing are proliferating and, for example, 8 different tests are available for detection, compared to zero for breast cancer.
  • Myriad has conducted extensive direct-to-consumer advertising which, studies indicate, significantly increased women’s interest in being tested for BRCA1 and 2, particularly among those at high risk for breast and ovarian cancer.

“Based on these latter points, it is, therefore, difficult to attribute reduced access to BRCA testing to patents. We cannot exclude the possibility that patent holders’ investments in education about hereditary breast and ovarian cancer and testing have actually had the opposite effect, of increasing access to testing,” conclude Dr Cook-Deegan and his co-authors.

The Next Round 

Whatever the actual effect of patents on patient access, the die is cast and the court of public opinion must now give way to judges’ deliberations. That hasn’t of course stopped everyone from speculating about what will happen. 

“I don’t think either side will be fully satisfied with the ruling that comes out of the court of appeals,” said Dr Cook-Deegan. “I think the court of appeals will decide that Judge Sweet got it right on the methods claims, and uphold his judgment on that. But I don’t think they’ll agree with him in ruling that you can’t patent DNA at all. That, at least on the surface, looks to be incompatible with decisions that the court of appeals has made over the years.”

James Evans, MD, PhD, is the Bryson Distinguished Chair of Human Genetics at the University of North Carolina-Chapel Hill and a member of the board of the American College of Medical Genetics. He wrote an editorial in Genetics in Medicine praising the analyses by Dr Cook-Deegan’s team and by Gold and Carbone, and pointing to a number of harms from diagnostic gene patents.3

“Patient access to testing can suffer, most clearly when exclusive providers fail to contract with insurers such as state Medicaid programs, leaving patients without the option of a given genetic test should it be recommended by their provider,” he wrote.

Dr Evans told Value-Based Cancer Care that the process unfolding in the courts may in fact fit with Myriad’s own business plan.

“On one hand, Myriad says that this is a broad decision, and that it has serious and problematic implications for genetic testing and diagnosis,” he said. “But on the other hand, they’re telling their shareholders—and I agree with them—that this isn’t the end of the world, that it’s not going to destroy their core business. My understanding of Myriad’s business plan is that it is based ultimately on therapeutics, which would have many downstream patents protecting it.”

Dr Cook-Deegan has a slightly different take on the future for Myriad.

“Their diagnostics patent protection will begin to expire in 4 years anyway, and so they will have to develop a less patent-dependent business model, and they appear to be positioned to do so with their current services,” he said. “They have long since been rewarded for having won the BRCA1 race by a couple months. As of March 29 they’ve had to compete on terms other than intellectual property-protected technology. Now let them compete.”

References

  1. Gold ER, Carbone J. Myriad Genetics: in the eye of the policy storm. Genet Med. 2010;12(4):S39-S70.
  2. Cook-Deegan R, DeRienzo C, Carbone J, et al. Impact of gene patents and licensing practices on access to genetic testing for inherited susceptibility to cancer: comparing breast and ovarian cancers with colon cancers. Genet Med. 2010;12(4):S15-S38.
  3. Evans JP. Putting patients before patents. Genet Med. 2010;12(4):S3-S4.