By Kevin E. Noonan --
One of the limitations of our judicial system is that it is inefficient in overcoming error. This drawback is most pronounced at the Federal Circuit, where precedential decisions can only be overcome by en banc reconsiderations, which (perhaps rightly) occur infrequently (and are not a guarantee that error will be rectified). Among the several Circuits there is at least the possibility of a Circuit split that will be resolved by the Supreme Court; while this may result in a remedy worse than the disease, at least the Court has the benefit of fully developed appellate decision making to provide context and legal argument in addition to the supplications of the parties (which necessarily and correctly are focused on their own interests).
At the Federal Circuit, in contrast, two judges can effectively produce a precedential decision binding on all future panels, unless and until the decision is reconsidered en banc. That is the situation with the Court's decision in In re BRCA1- & BRCA2-Based Hereditary Cancer Test Patent Litig., 774 F.3d 755, 760 (Fed. Cir. 2014), an immediately post-Myriad decision unduly restrictive of the scope of patent eligibility (as illustrated in Judge O'Malley's concurrence). That case involved the subject matter eligibility of oligonucleotide primers (for practicing the polymerase chain reaction or PCR) and methods for detecting BRCA gene mutations using these techniques. And the Court's decision was an almost knee-jerk application of the Supreme Court's decisions in AMP v. Myriad Genetics and Mayo Collaborative Services v. Prometheus Laboratories, creating (as is the Federal Circuit's wont) a bright line rule that nucleic acids were ineligible as natural products and diagnostic methods ineligible as natural laws (despite lip service to a mythic "something more" that would distinguish a patent-eligible method).
This situation made the decision in Roche Molecular Systems, Inc. v. Cepheid a foregone conclusion. The case arose in Roche's infringement case 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 involved in vitro culture of sputum specimens, which took several (3-8) weeks to produce a result, and could not specifically detect either M. tuberculosis cells or rifampin-resistant variants. The opinion notes, but does not expressly rely on, evidence that genotypic detection of a specific gene, rpoB, was a target for research by others at the time the invention was made. Researchers working for Roche and Mayo identified eleven "position-specific 'signature nucleotides'" by comparison of the gene sequence over several bacterial species, including M. tuberculosis.
Method and composition of matter (primer) claims were at issue; claims 1 and 17 are representative of each:
1. A method for detecting Mycobacterium tuberculosis in a biological sample suspected of containing M. tuberculosis comprising:
(a) subjecting DNA from the biological sample to polymerase chain reaction [PCR] using a plurality of primers under reaction conditions sufficient to simplify a portion of a M. tuberculosis rpoB [gene] to produce an amplification product, wherein the plurality of primers comprises at least one primer that hybridizes under hybridizing conditions to the amplified portion of the [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
a G at nucleotide position 2312,
a T at nucleotide position 2313,
an A at nucleotide position 2373,
a G at nucleotide position 2374,
an A at nucleotide position 2378,
a G at nucleotide position 2408,
a T at nucleotide position 2409,
an A at nucleotide position 2426,
a G at nucleotide position 2441,
an A at nucleotide position 2456, and a T at nucleotide position 2465; and
(b) detecting the presence or absence of an amplification product, wherein the presence of an amplification product is indicative of the presence of M. tuberculosis in the biological sample and wherein the absence of the amplification product is indicative of the absence of M. tuberculosis in the biological sample.
17. 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 claim 1].
The District Court granted summary judgment of invalidity for both types of claims for patent-ineligibility, and the Federal Circuit affirmed, in an opinion by Judge Reyna, joined by Judges Hughes and O'Malley (who wrote a perceptive concurring opinion). Judge Reyna, who also wrote the opinion in Ariosa v. Sequenom, substantially mimicked Judge Dyk's reasoning found in In re BRCA1, rejecting any distinction drawn by patentee Roche between the oligonucleotide primers and DNA as it occurs in nature; in this reasoning he cited Justice Thomas's conclusion that "mere isolation" did not change isolated DNA from naturally occurring DNA in the absence of a change in sequence. The opinion is careful to mention, in a footnote, that "[w]e do not address the subject matter eligibility of primers that have been altered—e.g., investigator-induced mutation(s) such that their nucleotide sequences are not found in nature, or primers which are chemically modified or labeled by investigators such that they cannot be isolated directly from naturally occurring DNA," citing Myriad. Nor did the synthetic nature of the oligos matter, a view consistent not only with the Court's decision in Myriad but also in cases that harken back to Cochrane v. Badische Anilin & Soda Fabrik (1877). And the eleven "position-specific 'signature nucleotides'" were also non-availing for eligibility, the opinion holding:
The eleven position-specific signature nucleotides on the MTB rpoB gene that Roche's primers are designed to hybridize to are naturally occurring; the Roche inventors identified these eleven positions after sequencing MTB DNA. . . . In other words, Roche identified these pre-existing position-specific signature nucleotides; it did not create them. 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].
Regarding the method claims, the Court used the "plain meaning" of the claim language to conclude that the claims were "directed to" the natural law that M. tuberculosis could be detected by PCR amplification of the sequence, stating that "[t]his 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." Having crossed the threshold of step 1 of the Mayo/Alice test for ineligibility, the opinion effortlessly satisfies the step 2 by finding PCR amplification to be "conventional, routine, and well-understood" and thus that the claims do not contain an "inventive concept." Mayo/Alice calculus complete, the Court holds the method claims to be patent-ineligible. And at least because this patent was written long before the current judicial regime antithetical to certain types of patents almost per se, it is easy for the panel to identify language in the specification supporting its conclusion:
This invention involves a comparative analysis of the rpoB sequences in MTB, other mycobacteria and related . . . bacteria . . . demonstrating the heretofore undiscovered presence of a set of MTB- specific position-specific "signature nucleotides" that permits unequivocal identification of MTB . . . [emphasis added].
(It should be noted if only for the record that this application of the law ignores the requirement from Diamond v. Diehr that the claims be considered as a whole. It was not "conventional, routine, and well-understood" to perform PCR amplification to detect the "position-specific 'signature nucleotides'" identified by these inventors, and thus at least one avenue for a court open to applying the law consistent with Diehr is once again avoided in this decision. Roche gamely made this argument, which the panel reduces to a mere "discovery" of a law of nature that is, per se, ineligible.)
In a pattern established by Judge Linn in Ariosa, Judge O'Malley penned a concurrence that reads more like a dissent, and contains one procedural and one substantive rebuttal of the Court's opinion. First, Judge O'Malley notes that the precedent upon which the Court relies, In re BRCA1, does not stand for the firmly established proposition that oligonucleotide primers and PCR amplification for diagnostic purposes are per se patent ineligible. She reminds her brethren that the question in In re BRCA1 was whether the District Court had abused its discretion in denying Myriad's motion for a preliminary injunction, not whether oligonucleotides are per se patent ineligible:
This 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—such as the question before the district court in BRCA1—presents a different type of inquiry than the question of whether an asserted claim is invalid—such as the question that was before the district court on summary judgment in this case. Indeed, "[w]hile the evidentiary burdens at the preliminary injunction stage track the burdens at trial, importantly the ultimate question before the trial court is different" because "[i]nstead of the alleged infringer having to persuade the trial court that the patent is invalid, at [the preliminary injunction] stage[,] it is the patentee, the movant, who must persuade the court that, despite the challenge presented to validity, the patentee nevertheless is likely to succeed at trial on the validity issue." Titan Tire Corp. v. Case New Holland, Inc., 566 F.3d 1372, 1377 (Fed. Cir. 2009). Significantly, "the trial court 'does not resolve the validity question, but rather must . . . make an assessment of the persuasiveness of the challenger's evidence, recognizing that it is doing so without all of the evidence that may come out at trial." Id. (emphasis added) (citations omitted).
This recognition significantly reduces the precedential effect of the BRCA1 decision and provides, perhaps, a way for a future panel to distinguish claims to primers from this precedent. 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.
Judge O'Malley's concurrence also notes that this case, unlike the BRCA1 case, contains unresolved questions of material fact that, while disregarded by the Court may provide another basis for distinguishing the BRCA1 decision. Citing the distinctions drawn by the Supreme Court in Myriad between genomic DNA and cDNA, Judge O'Malley opines that while the BRCA1 opinion sets forth the basis for finding the PCR primer claims to be patent ineligible, "it is not clear from the BRCA1 opinion or record why we reached this conclusion. The lack of record evidence underlying BRCA1's conclusion on this point is important in light of the record in this case." She then goes on to recite 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). All these facts were adduced from expert testimony and thus for Judge O'Malley raise "genuine issue of material fact" that are not appropriate for summary judgment. 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 this concurring opinion is a welcome ray of sunshine on a cloudy day, the practical effects of this, like so many Federal Circuit decisions on eligibility, is to incentive non-disclosure of inventions such as these, with the concomitant injury to progress that trade secret protection of diagnostic methods is almost certain to create. It should be self-evident that this outcome is contrary to the Constitutional mandate underlying the patent system, but it appears the current constitution of the Court is unconcerned with this outcome. Perhaps Chief Judge Woods of the Seventh Circuit was right after all.
Roche Molecular Systems, Inc. v. Cepheid (Fed. Cir. 2018)
Panel: Circuit Judges O'Malley, Reyna, and Hughes
Opinion by Circuit Judge Reyna; concurring opinion by Circuit Judge O'Malley