Clarity on patent subject matter eligibility is still being sought five years after Mayo[1] and three years after Alice[2]. Further adding to the confusion is the fact that discoveries in diagnostics, despite their apparent importance to the biomedical sciences, have been repeatedly determined as ineligible subject matter under 35 USC § 101. The two step Alice/Mayo test has increased the percentage of invalid patents, and the decision by the Supreme Court to deny certiorari in the case of Ariosa vs. Sequenom[3] in 2016 means we are unlikely to see a reversal of this trend in the near future. Inventors are still finding it challenging to implement the current guidelines toward a successful diagnostics patent grant. In this piece we provide perspective from a 2016 Federal Circuit decision that provides some over-looked hints for moving forward with inventions relating to diagnostics.

Three high-profile cases have pushed inventors of clinical diagnostic tools into a more restricted path of subject matter eligibility: the Supreme Court’s Myriad[4] decision, and two cases out of the Federal Circuit, Sequenom and Genetics Technologies Ltd.[5]. All of these cases involved broad clinical diagnostic innovations, instead of focusing on the specific research methods they created. The first of these, Myriad, was a landmark case that reversed contemporary policy on isolated gene patentability. The Supreme Court not only decided that isolated genes were not patent eligible, but also that the comparison of an isolated gene to a control gene represented an abstract idea, and was therefore also ineligible. The second decision restricting patent eligibility came from the Sequenom case, in which a “significant contribution to the medical field” which represented a truly novel discovery was dismissed as patent ineligible. The discovery, that “cell-free, fetal DNA” (cffDNA) was present in maternal blood, represented a major advancement and clearly deviated from the prior art. The merits of the discovery are still relevant in the use of diagnostic tests, as cffDNA is becoming a more reliable and common non-invasive early pregnancy procedure to diagnose genetic abnormalities. However, the court held that no transformation of “the nature of the claim” into “a patent eligible application” was present, based on the concept that the discovery was simply harnessing an observable natural phenomenon and applying well known assays toward that discovery. The third of these decisions, Genetics Technologies, dealt with a patent regarding coding DNA (protein-creating) and junk DNA (non-protein creating), which could be inherited together at higher than expected frequencies. This finding could be used to selectively analyze junk DNA instead of coding DNA and provide the basis of diagnostic tests for genetic conditions. The patent was deemed invalid due to this being a “law of nature”. These cases focused on the clinical impact, rather than on the specific breakthrough research methods involved.

From an overly simplified view, diagnostic tools can be broken down into finding new methods to isolate pure samples (laws of nature), determining changes in those samples in pathological conditions (a natural phenomenon) and comparing the results to non-pathological samples (an abstract idea) – i.e. the three judicially created exceptions to patent subject matter eligibility. By this rudimentary breakdown, there can be almost no new protected innovations in diagnostics. However, a case tangentially related to diagnostics, Rapid Litigation Management Ltd., v. Cellzdirect, Inc.[6], offers significant insight into a clearer path toward patent eligibility. Although it has been over a year since the Federal circuit ruling, the guidance provided by this important case can have far reaching implications and provide a clearer path forward for diagnostics.

The Federal Circuit Court of Appeals ruled in favor of the patentee, providing insight into eligible subject matter as it relates to the Alice/Mayo test. The patentee claimed a new way of freezing down and preserving hepatocytes, liver cells that have a wide range of uses in research and clinical settings. A key difference in the Rapid Litigation case is that the wording of the claim applies its discovery of a law of nature toward a laboratory technique. The claim in this case referred to hepatocytes frozen down multiple times as a method for laboratory refinement and potential diagnostic testing. In its most basic form, the claim describes a natural phenomenon – hepatocytes can survive multiple freeze-thaw cycles. Given the decisions in the earlier cases, this claim alone would likely be enough to be deemed ineligible in the current environment. However, the additional novel steps of purification and refreezing were not obvious given the prior art. Similar to the Sequenom finding, the Rapid Litigation claim (1) directed to a “law of nature”, (2) was non-obvious given the prior art, and (3) relied heavily on established methods. The difference between the Sequenom finding and the finding in the Rapid Litigation case is the application toward which each invention was ultimately aimed. Many diagnostic tests face similar hurdles which can require a new approach to ensure successful patent protection. Although clinical impact may provide weight to the importance of an invention, focus on the underlying laboratory methodology can lead this new approach by focusing on the novelty and practical use.

Although one path to better ensuring eligibility for diagnostic patent claims may be to include treatment options, this path could be restricted toward a single treatment paradigm and become quickly irrelevant as new treatments arise. Summing up the lessons from the cases mentioned above, patents aimed toward new diagnostic tests should not: (1) rely solely on genetic identification or pathology, (2) harness common assays to compare patient information to a standard, (3) rely on the discovery or levels of a pathologically correlated molecule, or (4) be based on any non-synthetic or simply observable method of detection, even if that method is novel. Therefore, rather than examining treatment options, inventors should explore placing their inventions in the context of laboratory research methodology. For instance, if the application of the Sequenom finding related their purification of cffDNA into a lab method for non-invasive preparation and storage of purified fetal DNA by freezing down maternal cells or plasma as a storage system, and then using that material for purification and later use, the novelty of separation from the maternal plasma may have been enough to qualify under the second step of the Alice/Mayo test.

Although dramatic changes to the Alice/Mayo framework may still occur, inventors will need to live in the current eligibility environment for the time being. Recent failures for diagnostic cases can be used as a guide for protecting new discoveries and inventions. Unlike uncertain clinical treatments or new biomarkers, refined laboratory methods, as per Rapid Litigation, could provide a critical outlet for inventors.