Ever since the Supreme Court's decision in Mayo Collaborative Services v. Prometheus Laboratories was handed down in 2012, diagnostic method claims have been routinely invalidated by the district courts and those decisions upheld by the Federal Circuit. Indeed, in her recent dissent of the Court's denial of patentee's petition for rehearing en banc in Athena Diagnostics v. Mayo Collaborative Services, Judge Newman enumerated the six (now, seven including Athena) Federal Circuit decisions holding diagnostic method claims to be patent ineligible under Section 101. In her dissent in Athena, Judge O'Malley noted that:
Since Mayo, every diagnostic claim to come before this court has been held ineligible. While we believe that such claims should be eligible for patent protection, the majority of this court has definitively concluded that the Supreme Court prevents us from so holding. No need to waste resources with additional en banc requests. Your only hope lies with the Supreme Court or Congress. I hope that they recognize the importance of these technologies, the benefits to society, and the market incentives for American business. And, oh yes, that the statute clearly permits the eligibility of such inventions and that no judicially-created exception should have such a vast embrace. It is neither a good idea, nor warranted by the statute. I dissent.
A bleak prospect, to say the least.
But as Justice Breyer mentioned in Mayo, the Supreme Court's eligibility precedent has cautioned "against interpreting patent statutes in ways that make patent eligibility "depend simply on the draftsman's art" without reference to the "principles underlying the prohibition against patents for [natural laws]" citing Parker v. Flook, 437 U. S. 584, 593 (1978). And yet, experience has shown time and again that adapting to the Court's shifting precedents requires competent draftsmen to use their experience and skill as draftsmen to capture for inventors claims to provide protection against expropriation by infringers. See, e.g., Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals.
The latest example of creative drafting (including how the invention was described in the specification) is a recent decision (Report and Recommendation [to the District Court judge]), by Magistrate Judge Christopher J. Burke in the District of Delaware, who denied defendant's Rule 12(b)(6) motion (of ineligibility) in CareDX, Inc. v. Natera, Inc. The case arose over the claims in U.S. Patent Application Nos. 8,703,652 and 9,845,497, directed to "methods to help predict the status or outcomes of transplant recipients through sequencing of cell-free nucleic acids ("cfDNA") found in the bodily fluids of a recipient." The rationale behind the invention is rejection of a transplanted organ in a recipient is accompanied by cell death, which releases donor-specific DNA into the recipient's bodily fluids. Claim 1 of the '652 patent and claim 1 of the '497 patents are representative:
The '652 patent claim 1:
1. A method for detecting transplant rejection, graft dysfunction, or organ failure, the method comprising:
(a) providing a sample comprising cell-free nucleic acids from a subject who has received a transplant from a donor;
(b) obtaining a genotype of donor-specific polymorphisms or a genotype of subject-specific polymorphisms, or obtaining both a genotype of donor-specific polymorphisms and subject-specific polymorphisms, to establish a polymorphism profile for detecting donor cell-free nucleic acids, wherein at least one single nucleotide polymorphism (SNP) is homozygous for the subject if the genotype comprises subject-specific polymorphisms comprising SNPs;
(c) multiplex sequencing of the cell-free nucleic acids in the sample followed by analysis of the sequencing results using the polymorphism profile to detect donor cell-free nucleic acids and subject cell-free nucleic acids; and
(d) diagnosing, predicting, or monitoring a transplant status or outcome of the subject who has received the transplant by determining a quantity of the donor cell-free nucleic acids based on the detection of the donor cell-free nucleic acids and subject cell-free nucleic acids by the multiplexed sequencing,
wherein an increase in the quantity of the donor cell-free nucleic acids over time is indicative of transplant rejection, graft dysfunction or organ failure, and wherein sensitivity of the method is greater than 56% compared to sensitivity of current surveillance methods for cardiac allograft vasculopathy (CAV).
The '497 patent claim 1:
1. A method of detecting donor-specific circulating cell-free nucleic acids in a solid organ transplant recipient, the method comprising:
(a) genotyping a solid organ transplant donor to obtain a single nucleotide polymorphism (SNP) profile of the solid organ transplant donor;
(b) genotyping a solid organ transplant recipient to obtain a SNP profile of the solid organ transplant recipient, wherein the solid organ transplant recipient is selected from the group consisting of: a kidney transplant, a heart transplant, a liver transplant, a pancreas transplant, a lung transplant, a skin transplant, and any combination thereof;
(c) obtaining a biological sample from the solid organ transplant recipient after the solid organ transplant recipient has received the solid organ transplant from the solid organ transplant donor, wherein the biological sample is selected from the group consisting of blood, serum and plasma, and wherein the biological sample comprises circulating cell-free nucleic acids from the solid organ transplant; and
(d) determining an amount of donor-specific circulating cell-free nucleic acids from the solid organ transplant in the biological sample by detecting a homozygous or a heterozygous SNP within the donor-specific circulating cell-free nucleic acids from the solid organ transplant in at least one assay,
wherein the at least one assay comprises high-throughput sequencing or digital polymerase chain reaction (dPCR), and
wherein the at least one assay detects the donor-specific circulating cell-free nucleic acids from the solid organ transplant when the donor-specific circulating cell-free nucleic acids make up at least 0.03% of the total circulating cell-free nucleic acids in the biological sample.
The Magistrate Judge resolved the issue of whether these claims were ineligible for patenting under 35 U.S.C. § 101 under the first step of the Supreme Court's test enunciated in Mayo and Alice Corp. v. CLS Bank Int'l. Defendants argued (as they must) that the claims in the patents-in-suit were directed to one of the judicial exceptions (a natural phenomenon, specifically "the correlation between transplant rejection and the presence of naturally occurring [cfDNA] in the bodily fluids of transplant recipients"). The Magistrate, relying on Federal Circuit precedent permitting a court to consider the patent specification in determining "what a patent claim is really directed to at step one [of the Mayo/Alice test]" (Enfish LLC v. Microsoft Corp.) found that:
"[T]he patents' [related] specification repeatedly and consistently states that this basic 'correlation' between the presence of increased levels of donor-specific cfDNA and transplant rejection . . . – i.e., the thing that, according to Defendants, the asserted claims were purportedly 'directed to' – had already been well-known in the art for quite a long time.
The Magistrate's findings further explicated disclosure in the specification related to prior art efforts to use distinguishing markers from donor DNA (Y chromosome sequences from male donors in female recipient, or HLA antigens that differed between donors and recipients) and how those efforts had failed.
The Magistrate then raised this rhetorical question: "How could it be the case that the 'basic thrust or 'character as a whole' or 'focus' of the purportedly representative claims of the patents is to a naturally-occurring correlation, when the patentee repeatedly states that this very correlation was already well-known in the art? To ask the question is to answer it," according to the Magistrate, further stating "[i]t does not, in fact, make a lot of sense to think that the claims are directed to something the patent repeatedly says the claims are not directed to." Relying further on the specification, the Magistrate credits the patentee for "tell[ing] us that what it thinks was really invented here . . . is something other than the correlation itself":
[T]he invention provides a universal approach to noninvasive detection of graft rejection in transplant patients which circumvents the potential problems of microchimerism from DNA from other foreign sources and is general for all organ recipients without consideration of gender. In some embodiments, a genetic fingerprint is generated for the donor organ. This approach allows for a reliable identification of sequences arising solely from the organ transplantation that can be made in a manner that is independent of the genders of donor and recipient.
The Magistrate concludes from his analysis that "what the inventors were focused on here was how to develop a new, more accurate and useful analytic method of determining whether significant amounts of cfDNA were present in a transplant recipient's body(so that one could then make use of the known correlation between that fact and indication of transplant rejection)" (emphasis in Report).
The Magistrate does not rely solely on these distinctions, however. The Report goes on to identify the language in the claims reciting detection methods that are not "routine, conventional, and well-understood": specifically, digital PC/high-throughout sequencing/ multiplex sequencing methods. (In footnote 8, the Magistrate states that "the key point here for purposes of Alice's step one is that the claims appear to be 'directed to' these particular methods for detecting – and not to the fact or existence of the natural phenomenon itself" (emphasis in Report)).
Accordingly, the Magistrate concludes that Defendants failed to meet their burden and recommends that the District Court judge deny the motion; tellingly, the Magistrate cites the Federal Circuit's Rapid Litig. Mgmt. Ltd. v CellzDirect Inc. decision in supporting the distinctions he relied upon here in making his Recommendation.
As refreshing as this opinion is, the reality is that it is a Report and Recommendation and thus one that the District Court judge may not follow (and Defendants are sure to make a case that the Judge should not follow it). The Magistrate Judge's description of how the draftsman disclosed the invention is reminiscent of the philosophy employed by judo practitioners, who use an opponent's mass and momentum to gain an advantage. By acknowledging the conventionality of the natural phenomenon underlying the invention, the issue of what the claims were "directed to" under the Mayo/Alice analytical framework could be decided in their favor. This is important, because the test is to be applied sequentially: if a defendant cannot satisfy the first, "directed to" prong, a court should not have the occasion to address the second prong relating to whether the recited detection method(s) were "routine, conventional, and well-understood." This approach also has the benefit of "grasping the nettle" of the tendency to blend other, prior art-related sections of the patent statute, thereby vitiating their effectiveness of blurring the statutory distinctions into a rhetorical mess. It cannot be said that this approach is a universal one, but it illustrates the wisdom of never acquiescing to the current state of patent eligibility jurisprudence so long as artful drafting (specification and claims) can permit a patentee to prevail.
CareDX, Inc. v. Natera, Inc. (D. Del. 2020)
Report and Recommendation by Magistrate Judge Burke