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Roche Patent Invalidation Affirmed in TB Testing Lawsuit Against Cepheid

NEW YORK (GenomeWeb) – The United States Court of Appeals for the Federal Circuit this week handed down a ruling in the case of Roche Molecular Systems, Inc. v. Cepheid affirming a district court's previous ruling invalidating a US patent assigned to Roche covering PCR-based methods for detecting Mycobacterium tuberculosis (MTB) and drug resistance.

Roche had sued Cepheid in the US District Court for the Northern District of California in July 2014, claiming that Cepheid had infringed on Roche's US Patent No. 5,643,723, entitled "Detection of a genetic locus encoding resistance to rifampin in mycobacterial cultures and in clinical specimens," through the development, commercialization, and sale of Cepheid's Xpert MTB/RIF assay in the US.

The patent, which Roche referred to in its complaint as the Persing patent, had David Persing listed as its lead inventor. Persing was a former faculty member and director of the Mayo Molecular Microbiology Laboratory at the Mayo Clinic, and was serving at the time as Cepheid's chief medical and technology officer. The patent was filed in May 1994 and awarded in July 1997, and was dually assigned to the Mayo Foundation for Medical Education and Research and Roche. Cepheid was acquired by Danaher in 2016.

In its original complaint, Roche noted that Cepheid entered into a cooperative research and development agreement with the Foundation for Innovative New Diagnostics to develop a PCR-based test for detecting MTB and identifying rifampin resistance in human sputum samples. Roche claimed that Cepheid's Xpert MTB/RIF assay comprised one or more primers claimed in the Persing patent, was especially adapted for practicing methods claimed in the Persing patent, and therefore infringed the patent.

The district court disagreed, however, ruling the patent invalid, based on the US Supreme Court's decisions in AMP v. Myriad Genetics and Mayo Collaborative Services v. Prometheus Laboratories which stated that nucleic acids are natural products and therefore not patentable. Roche appealed.

The appeals court affirmed the district court's ruling, noting "the asserted claims of the '723 patent are directed to patent-ineligible subject matter and are therefore invalid."

In regards to the primers themselves and whether they are naturally occurring, Roche had argued that the primers were patent-eligible because the patent referred to artificial, man-made primers that are different from naturally occurring DNA. Specifically, Roche argued that the patented primers have a 3-prime end and a 3-prime hydroxyl group, while naturally occurring bacterial MTB DNA doesn't. But the district court rejected Roche's arguments, noting that "the primer claims in this case, which have genetic sequences identical to those found in nature, are indistinguishable from those held to be directed to non-patentable subject matter." The appeals court concurred, writing, "BRCA1 forecloses Roche's arguments. There, this court examined the subject matter eligibility of similar primer claims and held that those primers 'are not distinguishable from the isolated DNA found patent-ineligible in Myriad' and thus are not patent-eligible."

Roche also argued that the specificity of its primers to the 11 signature nucleotides would transform them from naturally occurring into patent-eligible subject matter. But the court rejected this argument, saying that the primer wouldn't gain subject matter eligibility "simply because it can selectively hybridize to a certain position of naturally occurring DNA, because a primer having an identical nucleotide sequence to naturally occurring DNA without further chemical modification is a natural phenomenon."

Further, the court also found that the claims portions of the patent were invalid as they were "directed to a patent-ineligible natural phenomenon." The method claims asserted in the patent basically stated that if an investigator detected a signature nucleotide from a sample, the investigator would know that the sample contained MTB. "This relationship between the signature nucleotides and MTB is a phenomenon that exists in nature apart from any human action, meaning the method claims are directed to a natural phenomenon, which itself is ineligible for patenting," the court stated.

The ruling also noted that while it may be true that Roche's investigators were the first to ever use PCR to detect MTB in a biological sample, "being the first to discover a previously unknown naturally occurring phenomenon or a law of nature alone is not enough to confer patent eligibility. Many groundbreaking, innovative, and brilliant discoveries have been held patent-ineligible."

In a concurring ruling filed with the affirming ruling, appeals court judge Kathleen O'Malley noted that while she agreed with the decision to invalidate Roche's patent, she believed that the court should revisit its holding in BRCA1 with respect to the primer claims.

"Specifically, I believe that our holding there was unduly broad for two reasons: (1) the question raised in BRCA1 was narrower than our holding in that case; and, (2) our interpretation of the nature and function of DNA primers lacked the benefit of certain arguments and evidence that the patent owner presents in this case," she wrote.

O'Malley noted that the procedural context in the BRCA1 case was different and much broader than in the Roche case. Because of that, she argued, there was less evidence in that case and the arguments were formed on a different basis.

"Unlike the appellants in Myriad and in BRCA1, here, Roche submitted evidence of record that, at the very least, raises genuine issues of material fact as to whether there exists anything in nature that both has the structure and performs the function of the claimed primers," O'Malley wrote. For these reasons, while I agree with the majority that the broad language of our holding in BRCA1 compels the conclusion that the primer claims in this case are ineligible under 35 U.S.C. § 101, I believe that holding exceeded the confines of the issue raised on appeal and was the result of an underdeveloped record in that case. I believe, accordingly, that we should revisit our conclusion in BRCA1 en banc."