In a recent decision by the Federal Circuit, Roche Molecular Inc. v. Cepheid, the court raised for the first time a question regarding whether it may have over-interpreted the scope of the Supreme Court’s proscription regarding patenting compositions arising from products produced in nature in AMP v. Myriad Genetics.
The case arose over Roche's infringement allegations against Cepheid over U.S. Patent No. 5,643,723. The invention was directed to methods for detecting Mycobacterium tuberculosis in a human and in particular rifampin-resistant variants thereof. The claimed methods were recognized in the art and by the Court as an improvement on prior art methods (which had required in vitro culture of sputum specimens that took several (3-8) weeks to produce a result, and could not specifically detect either M. tuberculosis cells or rifampin-resistant variants). Researchers working for Roche and Mayo identified eleven "position-specific 'signature nucleotides'" by comparison of a specific gene, rpoB, over several bacterial species that included M. tuberculosis. Method and composition of matter (primer) claims were at issue, wherein the composition of matter claims recited:
A primer having 14–50 nucleotides that hybridizes under hybridizing conditions to an M. tuberculosis rpoB [gene] at a site comprising at least one position-specific M. tuberculosis signature nucleotide selected, with reference to FIG. 3 (SEQ ID NO: 1), from the group consisting of [the same 11 nucleotides at the positions disclosed in the specification].
The District Court granted accused infringer Cepheid summary judgment of invalidity based on patent ineligibility under Myriad, as that decision was interpreted by the Federal Circuit in In re BRCA1- & BRCA2-Based Hereditary Cancer Test Patent Litig., 774 F.3d 755, 760 (Fed. Cir. 2014). The Federal Circuit’s opinion rejected any distinction drawn by patentee between the oligonucleotide primers and rpoB gene DNA as it occurs in nature, despite the eleven "position-specific 'signature nucleotides'," because the patentee had merely “identified” these “pre-existing position-specific signature nucleotides” but “did not create them.” Consistent with its earlier decisions in this area, the opinion supported its decision by saying
“There is no doubt that Roche's discovery of these signature nucleotides on the MTB rpoB gene and the designing of corresponding primers are valuable contributions to science and medicine, allowing for faster detection of MTB in a biological sample and testing for rifampin resistance. However, "[g]roundbreaking, innovative, or even brilliant discovery does not by itself satisfy the § 101 inquiry," citing Myriad.
Despite the apparent conventionality of this decision, Judge O’Malley (the only Federal Circuit judge having district court experience) questioned in a concurring opinion whether the court had improperly excluded oligonucleotide primers from patent eligibility in its earlier BRCA1 and BRCA2 decision. The basis for her concern is that the question of patent eligibility had not been before the court in its earlier decision. There the question was whether the district court had properly denied Myriad’s motion for a preliminary injunction, which required Myriad to show it had a reasonable likelihood of showing its asserted primer claims were patent-eligible. She states that “[t]his procedural context in BRCA1 is important. We have routinely recognized that the question of whether an accused infringer has raised a substantial question of invalidity in the context of a motion for a preliminary injunction . . . presents a different type of inquiry than the question of whether an asserted claim is invalid . . ..” The distinction is relevant in this case because, as is always the case, an accused infringer has the burden of establishing, but clear and convincing evidence, that a patent claim asserted against it is invalid, where in the preliminary injunction context the patentee has the burden of establishing a likelihood that its asserted claims are not invalid. Judge O'Malley reminds her colleagues and us that the BRCA1 decision did not rule on the patent eligibility of PCR primer claims and does not compel the result the Court announced here. This recognition significantly reduces the precedential effect of the BRCA1decision and provides, perhaps, a way for a future panel to distinguish claims to primers from this precedent.
Also important for Judge O’Malley are the factual distinctions argued by Roche regarding the differences between the claimed primers and the sequences as they occur in nature (including the differences in strandedness, complementarity ("a primer comprising a nucleotide sequence of ATCG is complementary to, but unquestionably different from, a natural DNA strand comprising a sequence of TAGC"), the presence of a 3' hydroxyl group, the linearity of the primers versus the circular nature of bacterial DNA, and that natural "primers" comprise RNA and not DNA). Judge O'Malley also notes that the claimed primers here have a markedly different function, unlike the genomic DNA in Myriad, due to the presence of the 3' hydroxyl group which permits PCR amplification to occur. Judge O'Malley apprehends that the patentee in this case raised factual issues not addressed in the Court's BRCA1 decision, and thus, "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." Accordingly, she believes not only that the BRCA1 decision does not compel the Court's conclusion here, but that the question should be taken up en banc to clarify the law regarding the patent eligibility of oligonucleotide primers and perhaps methods of using such primers to amplify targeted portions of DNA.
While Judge O’Malley’s opinion is a welcome ray of sunshine on a cloudy day, the practical effects of her opinion, for now, does not change the inclination of the Court to deem any DNA that can be characterized as “merely isolated” to be ineligible for patent protection.
Kevin Noonan is a partner with the law firm McDonnell Boehnen Hulbert & Berghoff LLP and represents biotechnology and pharmaceutical companies on a myriad of issues. A former molecular biologist, he is also the founding author of the Patent Docs weblog, https://patentdocs.typepad.com/.
