Originally published Aug. 21.
Pleased with the federal appeals court's recent decision to uphold gene patents related to its BRACAnalysis test, Myriad Genetics took the opportunity last week to correct a few "common misconceptions" about the impact such patents might have on patients' access to genetic testing.
The Court of Appeals for the Federal Circuit in a two-to-one decision last week upheld Myriad's patent claims covering complementary DNA and isolated gene sequences. These patents are a critical part of the company's intellectual property suite and enable it to be the sole provider of clinical BRCA genetic testing for gauging patients' risk for hereditary breast and ovarian cancer (see related article, in this issue).
In the case, Association for Molecular Pathology et al. vs. the United States Patent and Trademark Office et al., patients, women's health groups, researchers, and healthcare providers – represented by the American Civil Liberties Union and the Public Patent Foundation – are challenging Myriad's patents on diagnostic methods, cDNA, and isolated gene sequences related to its BRACAnalysis test. In the course of the case, the plaintiffs have charged that Myriad's patents, covering short fragments and broad stretches of the BRCA1 and BRCA2 genes, preempt natural laws, which are not patent eligible under US law. These patents, plaintiffs say, hinder researchers from using that molecular knowledge in other studies, bar doctors from performing testing to give patients a second opinion after receiving BRACAnalysis test results, and create a monopoly that enables Myriad to charge high prices for its tests.
Myriad feels these accusations are without merit. "It is important to correct some common misconceptions on the societal impact of 'gene' patents; namely that such patents impede research, result in high-cost testing and take away a patient's option for second-opinion testing," the company said in a statement that aimed to "set the record straight" following the CAFC's ruling in AMP v. USPTO. "Myriad believes that statements made to these points in the public press are incorrect."
Impact on Research
With regard to the charge that Myriad's patents impede research, the company highlighted that around 18,000 scientists have conducted studies on BRCA genes and have published more than 9,000 papers. Based on these statistics, which Myriad has cited throughout the course of the lawsuit, the firm claims that it is not exercising its patents in an effort to hold back research advances in the way plaintiffs in AMP v. USPTO have alleged.
Several plaintiffs in the case who are researchers have said that when they tried to offer BRCA testing, Myriad sued, threatened to sue, or asked their labs and institutions to sign licensing agreements, which caused them to stop testing. Furthermore, genetics researchers Harry Ostrer, formerly at New York University, and Wendy Chung at Columbia University, have said that although they are conducting BRCA gene sequencing in a research setting, Myriad's patent position restricts them from informing study participants of test results. If clinical investigators were to report the diagnostic results from BRCA tests to study subjects, then it would cease to be research in Myriad's view and the firm would seek payment for each "testing service," the company informed Ostrer in a licensing letter several years ago.
Ellen Matloff, another plaintiff in AMP v. USPTO and director of cancer genetic counseling at the Yale Cancer Center, has also recounted that before Myriad began offering a separate test to gauge certain large rearrangements in BRCA1 and BRCA2 genes, called the BRACAnalysis Large Rearrangement Test (BART), she and her colleagues at the university had data showing that the company's so-called Comprehensive BRACAnalysis test was missing a "significant percentage" of mutations in patients. Her group asked Myriad's permission to offer large rearrangement testing to patients at the cancer center until the companpy launched BART, but Myriad didn't grant it (PGx Reporter 8/3/2011).
The CAFC in its latest ruling found Ostrer, who is currently employed at Yeshiva University, to be the only plaintiff who "alleges a sufficiently real and imminent injury," since he has stated that he intends to "immediately" begin BRCA testing if Myriad's patents were invalidated. Myriad has sought to have the case dismissed, asserting that its efforts to stop others from performing BRCA testing outside of research occurred a decade ago and none of the plaintiffs can point to actual harm caused by its patents.
Still, in his majority opinion, federal circuit court judge Alan Lourie recognized that "Myriad’s active enforcement of its patent rights forced Ostrer, as well as every other similarly situated researcher and institution, to cease performing the challenged BRCA testing services, leaving Myriad as the sole provider of BRCA clinical testing to patients in the US." Lourie further noted that "nothing in the record suggests that any researcher or institution has successfully attempted to compete with Myriad, or that Myriad has in any way changed its position with regard to its patent rights."
Price and Access
In its statement following the CAFC ruling, Myriad also asserted that the $3,340 list price for the BRACAnalysis test "is not prohibitive and patient access is extensive." The company says that out of the nearly one million patients who have been tested with BRACAnalysis, "95 percent of appropriate patients" have their test costs covered by private insurance or under Medicare or Medicaid. The company highlighted that over the last three years it has covered the cost of BRACAnalysis for 5,000 low-income or uninsured patients through its financial assistance program.
Many patient advocates and healthcare providers believe, however, that Myriad's BRACAnalysis test is priced too high and its monopoly of BRCA testing for breast and ovarian cancer has allowed it to steadily increase the price of its test. For example, organizations such as Facing Our Risk of Cancer Empowered, the Yale Cancer Center, and numerous others have petitioned Myriad to include analysis of cancer-linked large rearrangements in the BRCA1 and BRCA2 genes as part of its Comprehensive BRACAnalysis test.
However, Myriad sells its Comprehensive test and BART separately, charging $700 for the latter diagnostic on top of the $3,340 for the former (PGx Reporter 8/15/2012). Company officials recently highlighted that Myriad holds patents related to BART that will provide intellectual property protection against competitors until 2025.
Myriad believes that data from a 25,000-patient study showing the importance of certain BRCA large rearrangements in breast and ovarian cancer susceptibility will convince many insurers to cover BART and limit out-of-pocket costs for patients. The company estimates that although the list price for BRACAnalysis is more than $3,000, with insurance coverage patients on average pay less than $100 out of pocket.
However, insurers will likely only pay for patients for whom they deem the test medically necessary. Although treatment guidelines recommend BART for all women who qualify for BRACAnalysis, most insurers cover BRACAnalysis under a prior authorization scheme in order to make sure that only patients who have a medical and family history of breast and ovarian cancer receive the test. In the past, insurers have expressed concern that around 20 percent of women in their plans were receiving testing when they shouldn't have (PGx Reporter 9/22/2010).
Confirmatory Testing
Myriad's statement last week also took issue with critics who claim its patents limit the availability of confirmatory testing. Contrary to these claims, "second opinion testing is available for patients with positive test results in a number of US laboratories, including a large reference laboratory licensed by Myriad in 2001," the company said. In AMP v. USPTO, at least one plaintiff, Genae Girard, charged that Myriad's patent position limited her ability to get a second genetic test to double check the results from BRACAnalysis.
Under the America Invents Act, a patent reform law enacted last September, the USPTO is required to prepare a report on secondary genetic testing and submit it to Congress this year. The USPTO hosted two meetings this year to gather public input on whether gene patents and exclusive licenses have limited patients' access to confirmatory testing from independent diagnostic providers (PGx Reporter 2/22/2012).
In its written comments for the USPTO meetings, the company noted that the National Center for Biotechnology Information's Genetic Testing Registry lists a number of US labs that offer second opinion BRCA testing, including the UCLA Diagnostic Molecular Pathology Laboratory, the University of California San Francisco Molecular Diagnostic Laboratory, and the University of Chicago Genetic Services Laboratory.
The written comments added that Myriad in 2002 licensed to Laboratory Corporation of America the right to conduct single-site and multi-site BRCA testing as part of its Ashkenazi Jewish Panel.
LabCorp's test menu no longer includes single-site BRCA testing, however. Myriad acknowledges this in its USPTO documents, adding that if the lab no longer offers the test, "it only further adds to the evidence that there is no significant level of demand for confirmatory testing."
A Myriad spokesperson couldn't confirm whether the lab was actively providing such a service at this time. A call to LabCorp was not returned.
Some experts who regularly interact with cancer patients and their families, such as FORCE Executive Director Sue Friedman, said they were unaware that Myriad had granted other labs licenses to perform confirmatory BRCA testing and indicated that this may not be well known among most women in a position to want such analysis.
Yale's Matloff was aware that confirmatory testing is available from certain labs for patients who test positive with BRACAnalysis. "Some labs do offer limited testing of BRCA1 and BRCA2," Matloff said. In these cases, they offer "not full sequencing of the entire gene, but just for the mutation found in a specific family."
However, Matloff highlighted that Myriad's statement following the CAFC's AMP v. USPTO decision stresses the availability of confirmatory BRCA testing for patients with positive test results, but doesn't say whether it is available for the majority of patients who get a negative result.
Likewise, Sandra Park, staff attorney with the ACLU Women's Rights Project, pointed out to PGx Reporter that Myriad's statement does not address the availability of confirmatory testing in the case of negative test results. In their attempt to do away with gene patents, plaintiffs in AMP v. USPTO hope to clear the path for more labs to offer BRCA testing and increase testing options for patients.