The ability of life sciences companies to rely on patent protection for diagnostic methods has been eroded over the last ten years, although recent court decisions evidence a rebuilding framework. While courts have consistently invalidated diagnostic methods as lacking patent eligibility, claims re-framed as methods of treatment that include a diagnostic step have recently been deemed to be patent-eligible subject matter. In its recent decision in Illumina v. Ariosa, the Federal Circuit confirmed that another category of claims – methods of preparation – are patent- eligible, providing a new opportunity to cast diagnostic method claims in a patent-eligible light. The Court’s decision offers promise for patent applicants pursuing patent protection for COVID-19 and other diagnostic methods.
35 U.S.C. Section 101 of the Patent Act codifies that “any new and useful process, machine, manufacture, or composition of matter” is patent-eligible, but judicial exceptions prohibit patent claims directed to a law of nature, a natural phenomenon or an abstract idea. Courts have established a two-step “Alice/Mayo” test to determine whether claimed subject matter is patent- eligible. Step One asks whether a claim is directed to one of the judicial exceptions. If so, Step Two asks whether the elements of the claim transform the prohibited judicial exception into a patent-eligible application.
Courts generally consider the use of conventional techniques insufficient to transform a claim into a patent-eligible application. However, claims that include additional features that assure the processes are genuine applications of a natural phenomenon, rather than drafting efforts designed to monopolize a correlation, may be patent-eligible. In view of court decisions, the United States Patent and Trademark Office (USPTO) has issued guidelines to evaluate whether a claim that includes a judicial exception may nonetheless be patent-eligible if the claim recites additional limitations that integrate the judicial exception into a practical application.
In implementing the evolving framework, courts have found that diagnostic method claims directed primarily to a correlation that exists in nature relate to a natural phenomenon, and are therefore not patent-eligible. In the now famous 2015 Ariosa v. Sequenom decision, the Federal Circuit held that claims to a method of detecting fetal DNA in a mother’s serum or plasma sample were patent-ineligible, as being directed to a natural phenomenon. In its opinion, the Court acknowledged that the discovery of cell-free fetal DNA (cffDNA) present in a mother’s circulating blood was a major scientific breakthrough; this finding allowed fetal genetic abnormalities to be analyzed from a blood sample of a pregnant woman, thereby avoiding the risks associated with obtaining a sample from the fetus or placenta. Still, the claims were ultimately found to be primarily directed to a natural phenomenon – the presence of fetal DNA in a mother’s serum or plasma – and merely recited conventional techniques for detecting DNA, which failed to transform them into a patentable invention.
By contrast, other court decisions illustrate that method of treatment claims may be patent- eligible. For example, in Vanda Pharmaceuticals v. West-Ward Pharmaceuticals, the claim at issue was directed to the identification of a genetic variant that renders individuals poor metabolizers of a compound used to treat schizophrenia, and administering specific and different amounts of the compound to individuals, depending on whether they harbored the genetic variant. Similarly, in Endo Pharmaceuticals v. Teva Pharmaceuticals, the claims were directed to treating pain in a renally impaired patient with a compound, wherein the creatinine clearance rate of the patient was measured, and a lower dosage of the compound was administered to the patient, depending on the patient’s clearance rate. The Court found the claims at issue in both of these cases to be patent-eligible, as being directed to “a specific method of treatment for specific patients using a specific compound at specific doses to achieve a specific outcome.” By incorporating additional features related to treatment, the claims represented practical applications of the underlying natural phenomena.
The Federal Circuit’s decision in Illumina v. Ariosa in March 2020, which was confirmed earlier this month in an updated decision, has now deemed patent-eligible certain other method claims related to analysis of fetal DNA. In a series of patent applications related to those that were the focus of Ariosa v. Sequenom discussed supra, Sequenom obtained two patents, now exclusively licensed by Illumina, to methods of preparing a fraction of DNA enriched in cffDNA. The claims recite steps of extracting DNA, producing DNA fragments by size discrimination and selectively removing DNA fragments larger than a particular size, and analyzing the DNA fragments. The methods of preparation are based on the inventors’ finding that fetal DNA fragments are, on average, smaller than maternal DNA fragments (a natural phenomenon). By selectively removing DNA fragments larger than 300 or 500 base pairs, the inventors were able to enrich the sample for fetal DNA.
Notably, the two patents were deep in prosecution at the time the related detection patent was found invalid by the Ariosa v. Sequenom 2015 decision. During prosecution, the preamble of originally filed claims reciting a “method of analyzing” DNA fragments was amended in response to a Section 101 patent ineligibility rejection to instead recite “a method for preparing” a DNA fraction. Other notable amendments were also made – the term “obtaining” was changed to “extracting,” and the terms “has been selectively removed” and “thereby removing” were changed to “selectively removing.” These amendments incorporating active and defined steps, rather than passive and generic steps, may also have laid the foundation for the Federal Circuit’s finding that the claims are patent-eligible.
In particular, the Federal Circuit, in its March 2020 decision, deemed the claims to be patent- eligible and distinguished them from the claims in Ariosa v. Sequenom by proclaiming, “This is not a diagnostic case. And it is not a method of treatment case. It is a method of preparation case.” In August 2020, the Federal Circuit denied Ariosa’s request for rehearing en banc and modified its earlier March decision. In its modified decision, the Court reiterated its earlier proclamation, but also further explained that the claimed DNA fragment size thresholds were “human-engineered parameters.” The Federal Circuit’s distinction between these cases demonstrates that claims based on a natural phenomenon, but not solely directed to the natural phenomenon itself, may be patent-eligible.
In carving out a new category of patent-eligible claims, the Court provided a roadmap, explaining that the claims were not directed to a natural phenomenon itself, but to its exploitation. In particular, the claims (1) involve specific process steps of size discrimination and selectively removing DNA fragments above a specified size threshold; and (2) include physical process steps that change the composition of the mixture, resulting in a DNA fraction different from that naturally occurring in the mother’s blood.
Taking the Federal Circuit’s decision as guidance, patent applicants may be able to protect diagnostic methods by framing them in a more specific or defined manner that exploits a natural phenomenon. For instance, this decision highlights that claims drafted as “methods of preparation” can be patent-eligible. In doing so, care should be taken to draft the claims in a way that highlights particular and human-engineered aspects of the method.
And, despite Mayo’s instruction that the use of conventional techniques may not be sufficient to transform a claim into a patent-eligible application, conventional techniques may be just fine. As the Federal Circuit explained in the instant case, conventional techniques – for example, general size discrimination of DNA fragments – can be used in unconventional ways, such as by overlaying human-determined parameters to change a composition. Thus, even if the method a patent applicant seeks to protect uses conventional steps, the applicant should consider whether the claims have been tailored in a way to exploit a new observation.
Although the reach of this decision remains to be seen, a line of Federal Circuit cases have now identified several categories of method claims, including “methods of treatment” and “methods of preparation,” that relate to patent-eligible diagnostic methods. These decisions offer hope to patentees in the diagnostics space that other method claims that relate to detection or analysis based on a natural correlation may also be patent-eligible if they recite specific or particular steps.
Finally, no strategy is without potential pitfalls. Claim drafters should carefully draft multi-step method claims, as they may be vulnerable to divided infringement, discussed in more detail in this article.
 35 U.S.C. § 101.
 See Mayo Collaborative Servs. v. Prometheus Laboratories, Inc., 566 U.S. 66 (2012); Alice Corp. Ptd. Ltd. v. CLS Bank Int’l, 573 U.S. 208, 217-18 (2014).
 Mayo Collaborative Servs. at 77.
 October 2019 Patent Eligibility Guidance Update available at https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_update.pdf.
 Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015).
 Vanda Pharmaceuticals, Inc. v. West-Ward Pharmaceuticals Int’l Ltd., 887 F.3d 1117 (Fed. Cir. 2018).
 Endo Pharmaceuticals Inc. v. Teva Pharmaceuticals Inc., 919 F.3d 1347 (Fed. Cir. 2019).
 Id. at 1354.
 U.S. Patent Nos. 9,580,751 and 9,738,931.