NEW YORK (GenomeWeb) – While industry observers might disagree about whether GeneDx's decision to apply for inter partes review (IPR) of 11 patents held by Myriad Genetics will work in its favor, they generally concur that it is a quicker and less costly strategy than litigation.
Myriad and co-owners of 16 patents underlying the firm's hereditary cancer risk tests filed a lawsuit last October alleging that BioReference Laboatories subsidiary GeneDx was infringing their IP. The patent holders are alleging that GeneDx is infringing claims describing diagnostic methods, primers, and probes used in genetic testing. As this case is ongoing in the US District Court for the District of Utah, Sterne Kessler, the law firm representing GeneDx, filed IPR applications last week, asking the US Patent and Trademark Office to assess whether 11 patents owned, co-owned, or licensed by Myriad are invalid on prior art grounds – meaning that the information related to the claimed invention was already publicly known before the patent filing date.
The patents GeneDx is challenging through IPR petitions relate to tests for gauging cancer risk based on mutations in three genes, BRCA1, BRCA2, and MUTYH, and include US patent numbers: 5,654,155; 5,753,441; 6,033,857; 6,051,379; 6,083,698; 6,951,721; 7,470,510; 7,563,571; 7,622,258; 7,670,776; and 7,838,237. These same patents are also at issue in the Myriad v. GeneDx lawsuit.
Doubtful that GeneDx's strategy will lead to success in the end, Kevin Noonan, prolific writer on biotech IP matters and a partner with McDonnell Boehnen Hulbert & Berghoff, acknowledged nonetheless that the IPR track is "probably [GeneDx's] best opportunity to knock out some of [Myriad's] claims" and a cheaper strategy than litigation.
In contrast, Robert Cook-Deegan, research professor of public policy, internal medicine and biology at Duke University, believes that the legal team at Sterne Kessler led by Jorge Goldstein may have "found another underbelly of Myriad's IP-based strategy." He expects that a "fair number of claims [held by Myriad], and some entire patents, will disappear" following the USPTO's IPR process.
To date, legal challenges to patents underlying Myriad's hereditary cancer tests, particularly the BRACAnalysis breast and ovarian cancer diagnostic, have focused on subject matter patent eligibility requirements set forth under Section 101 of 35 USC. This section of the law lays out that a claimed invention must be a new or useful process, machine, manufacture or composition of matter, but cannot be a law of nature, physical phenomenon, or an abstract idea.
The Supreme Court last year decided in Association for Molecular Pathology et al. v. Myriad that a number of Myriad's claims on naturally occurring isolated BRCA gene sequences were patent ineligible under Section 101. Meanwhile, the court upheld Myriad's claims on cDNA, reasoning that because they do not occur in nature, they did meet the standards under Section 101.
In that decision, the Supreme Court justices also indicated in a footnote that they "express no opinion whether cDNA satisfies the other statutory requirements of patentability" such as Section 102 or 103. Under Section 102 of the patent law, an inventor is required to show that the claimed invention was not previously patented, printed in publications, or in public use before the filing date. Section 103 requires that before the filing date of a claimed invention, it was not "obvious … to a person having ordinary skill in the art to which the claimed invention pertains."
In pursing IPR, the USPTO will assess whether the 11 patent claims pass muster under Section 102 and 103. If the USPTO agrees to review the patents, it will once again publicly air old, but enduring controversies in the scientific community about whether the content of Myriad's BRCA2 patents fail to pass muster under prior art grounds, given that around the same time in the mid-1990s, a UK team led by Michael Stratton from the Cancer Research Campaign had also published and filed patents related to the gene.
'The place that patents go to die'
After the Supreme Court's determination in AMP v. USPTO, GeneDx along with several other labs began offering BRCA tests, believing that the ruling opened up to competition a market previously monopolized by Myriad. However, Myriad quickly sued GeneDx and six other firms offering similar testing, asserting that it still had valid patent claims these companies were infringing. GeneDx is the first of the diagnostic shops engaged in litigation with Myriad to try to invalidate the contested patents using IPR – a new procedure established by the America Invents Act of 2011.
Under this pathway, USPTO's Patent Trial and Appeal Board decides within 18 months whether a granted patent is valid under Section 102 and 103. IPR review by the USPTO "will go comparatively quickly; probably, much faster than the pending litigation in Utah," Dan Burk, a law professor at the University of California, Irvine, and an expert in biotechnology and patent law told PGx Reporter. The patent office must first decide whether GeneDx's applications meet the technical requirements for IPR, and if so, will then hold hearings to gather testimony, depositions, and other information, before coming to a decision.
So far, in one of Myriad's lawsuits, the Utah federal district court has decided not to issue a preliminary injunction against Ambry Genetics. Although Judge Robert Shelby conceded that competition from Ambry might harm Myriad's hereditary cancer testing business, he wasn't convinced that Myriad and other patent owners were likely to succeed in their case alleging that Ambry's BRCA tests infringe several of their BRCA patents claims. Shelby's decision in March, however, didn't decide the patent eligibility of the claims at issue. That, as Myriad has pointed out many times, will take some time.
While under the patent reform act USPTO is required to issue a swift decision after an IPR, Courtenay Brinckerhoff, a partner and intellectual property lawyer with Foley & Lardner, pointed out that simultaneously taking on litigation and IPR is a challenging proposition and a possible reason why none of the other firms sued by Myriad have pursued it. "It's still a limited forum and a limited time frame in which to make your case," Brinckerhoff said of the IPR route. "It's also expensive having two proceedings going on at once. So, the other companies could be feeling like they have enough going on defending the litigation."
Meanwhile, one point in GeneDx's favor is the fact that the USPTO's Patent Trial and Appeal Board is known among industry players as the "place that patents go to die," Noonan pointed out. "The only reason that this is being done is because the Patent Trial and Appeal Board has this reputation of sort of looking to invalidate patents," he told PGx Reporter. "So, under the circumstances, does GeneDx have a chance [at success]? Yes, they have a much better chance than they would have in litigation because there you need 'clear and convincing evidence' and here [at the USPTO] you need 'a preponderance of evidence.'"
Similarly, in a statement, Sterne Kessler Director Eldora Ellison noted that "the [challenged] patents are not presumed valid at the USPTO during an IPR as they are in federal court."
Additionally, in reviewing patents under IPR, the USPTO will grant the broadest reasonable interpretation of the claim terms. This "expands the scope of the claim," Noonan said. "If you expand [the scope] you make the target bigger, and it's easier for someone to find a piece of prior art that's within the scope of the expanded claim."
Myriad has maintained that whether in court or before the USPTO Patent Trial and Appeal Board, it will continue to defend its patent suite. Spokesperson Ron Rogers noted that this will be the firm's first experience with the IPR process.
Reviving old controversies
In the race to clone, sequence, and identify gene mutations linked to hereditary breast cancer, the scientific community recognizes that the research team out of the University of Utah and Myriad Genetics finished ahead of Mary-Claire King's group and others around the world. However, what some researchers still question is whether Myriad was really first to characterize the location and role of BRCA2 in breast cancer.
In September 1994, in Science, a team led by the Cancer Research Campaign's Stratton published that the second breast cancer susceptibility locus, BRCA2, was located on chromosome 13q12-13. Then, in a December 1995 paper in Nature, Stratton's group reported on the first BRCA2 mutations associated with breast cancer risk.
"The scientific scuttlebutt has long been that Myriad scientists learned of the pending [Nature] publication and filed just in time," Cook-Deegan wrote in March in The Cancer Letter. "But was it really in time?"
A few days before that Nature paper came out, Myriad filed its first BRCA2 patent applications, and several months later in March 1996, it published a paper entitled, "The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds." Printed in Nature Genetics, the researchers led by Myriad founder Mark Skolnick wrote that the earlier British paper reported only a partial BRCA2 sequence and a handful of mutations. Meanwhile, the work by Skolnick and colleagues "have now determined the complete coding sequence and exonic structure of BRCA2 and examined its pattern of expression," as well as provided sequences for primers enabling screening of "the entire coding sequence of BRCA2 using genomic DNA," according to the paper.
In his Cancer Letter piece, Cook-Deegan further asserts that Stratton's group filed a UK patent application on BRCA2 on Nov. 23, 1995 (published on May 28, 1997) a month before Myriad's US patent application for BRCA2. Moreover, Stratton's group also got a US patent on BRCA2, but according to Cook-Deegan, the fees required to maintain that patent weren't kept up. The USPTO "is not supposed to grant overlapping claims," he wrote in The Cancer Letter, further questioning why the patent office didn't set up an "interference," a procedure for sorting out which party should be granted a patent when multiple applications claim the same thing filed around the same time.
Noonan also expects that all this history will be hashed out during the IPR process, acknowledging that in the race that led to the identification of BRCA2, Myriad and the UK researchers were "neck and neck." "The question is who ended up doing it first, because up until two years ago in the US if you did it first, you were entitled to the patent," he said.
In his "cursory" review of GeneDx's IPR applications, Noonan found that the company does cite some "prior art," describing knowledge that researchers had at the time about the possible involvement of a gene in breast cancer other than BRCA1, and the general areas of the chromosome it might be located in. However, it will still be challenging for GeneDx, he suggested, to provide a "preponderance of evidence" that knowledge of the precise location of the BRCA2 gene and mutations associated with breast cancer were prior art to the extent that Myriad's research elucidated before it filed its patent and published the paper.
"The thing that Myriad provided was that you had the gene, you had the mutations that were important, and you had the exactitude that you didn't have, really nothing close to it, before that," he said. Close to two decades later, "a lot of this is … what you coulda, shoulda, woulda done," Noonan said, further dismissing those who doubt Myriad's position as "sour grapes" and "academics." Noonan has blogged disparagingly of Cook-Deegan's piece in The Cancer Letter.
As an academic who has spent a large part of his career thinking and writing about how patents are impacting the field of genomic medicine, Cook-Deegan, for one, can't wait for the USPTO to take up the IPR applications. "I'm very much looking forward to the public record this will leave," he said.