The medical diagnostics market is expected to reach $74.2 billion by 2019. In 2012, the U.S. Supreme Court held that the Mayo Clinic had not infringed on Prometheus Labs’ diagnostic patent because the Prometheus patent involved ineligible subject matter. Mayo Collaborative Services v. Prometheus Labs., Inc., 566 U.S. 66, 70 (2012). The Patent Act defines patent-eligible subject matter as “any new and useful process, machine, manufacture, or composition of matter.” 35 U.S.C. § 101 (2012). However, since the Court’s unanimous decision in Mayo, the percentage of medical diagnostic patents allowed by the U.S. Patent and Trademark Office has dropped to less than 35 percent, as compared with 85 percent before Mayo. Kate Gaudry, Leslie Grab & Tina Williams McKeon, “Trends in Subject Matter Eligibility for Biotechnology Inventions,” IPWatchdog, June 12, 2015. Arguably, Mayo and its progeny have had a chilling effect on the multibillion-dollar medical diagnostic industry.
Novel disclosures provided during Markman, or claims construction, hearings may improve the survival of diagnostic patents. J. Michael Jakes, “Using an Expert at a Markman Hearing: Practical and Tactical Considerations,” IP Litigator, Aug. 2002. See generally, Markman v. Westview Instruments, Inc., 517 U.S. 370 (1996); Manual for Complex Litigation (Fourth) § 23.32 (noting that “in patent cases, expert disclosures relating to claims construction may be called for early in the case. . . .”). Courts have cautioned that claims construction must not begin and end with naturally occurring phenomena like the detection of plasma, BReast CAncer genes, blood cells, or pharmacokinetics. Despite this, some relatively recent cases have contained patent claims involving ineligible subject matter that was held to be invalid. This article updates a comment discussing keys to patent survival by reviewing more recent subject matter ineligibility cases. A critical step in survival is disclosure of (1) normative data, (2) procedural algorithms; (3) mathematical formulas; or (4) other transformative methods affecting reliability, sensitivity, validity, or specificity compared to other tests. Karen McKenzie, “NOA v. DOA: Increasing Medical Diagnostic Patentability After Mayo,” 22 Marq. Intell. Prop. L. Rev. 193 (2018).
First, in Cleveland Clinic Foundation v. True Health Diagnostics, the patent disclosed that plasma concentrations of C-reactive protein may predict the risk of some cardiovascular diseases. See 859 F.3d 1352 (Fed. Cir. 2017), cert. denied, 138 S. Ct. 2621 (2018). The court held that the claimed method “starts and ends” with the observation of “naturally occurring phenomena” and was therefore ineligible subject matter and invalid. Id. at 1360. Essentially, the detection of the protein was not subject matter eligible to provide a monopoly on this test for cardiovascular disease.
Second, claims construction should not begin and end with the naturally occurring phenomenon, the patient, or the patient’s cellular or physical reaction to a diagnostic test. In Athena Diagnostics, Inc. v. Mayo Collaborative Services, LLC, the court found that the claims were directed to a patent-ineligible concept. 915 F.3d 743 (Fed. Cir. 2019). Athena claimed to have invented a new lab technique to “detect autoantibodies in a sample of bodily fluids in accordance with immunological assay techniques known per se in the art,” such as radioimmunoassay. Id. at 748. In addition, a claim required that “the intensity of the signal from the [secondary] antibody is indicative of the relative amount of the anti-MuSK autoantibody in the bodily fluid when compared to a positive and negative control reading.” However, the court noted that this correlation between the “presence of naturally-occurring MuSK autoantibodies in bodily fluid and MuSK-related neurological diseases” like myasthenia gravis already exist in nature “apart from any human action.” Id. at 750. Therefore, the court found that “there can be no dispute that it is an ineligible natural law.” Id. Essentially, the addition of an isotope to the test did not cause a novel reaction to that which is already known in the art.
Third, claims construction should not begin and end with pharmacokinetics. See Jennifer Le, “Overview of Pharmacokinetics,” Merck Manual (May 2019) (noting that because of individual differences, drug administration must be based on each patient’s needs—“traditionally, by empirically adjusting dosage until the therapeutic objective is met. This approach is frequently inadequate because it can delay optimal response or result in adverse effects. Knowledge of pharmacokinetic principles helps prescribers adjust dosage more accurately and rapidly. Application of pharmacokinetic principles to individualize pharmacotherapy is termed therapeutic drug monitoring.”). In Endo v. Teva, the inventor developed a new method of treating pain by adjusting the dose of oxymorphone in patients whose kidney function was impaired. Endo Pharm. Inc. v. Teva Pharm. USA, Inc., 919 F.3d 1347 (Fed. Cir. 2019). The “invention provides methods using oxymorphone in the treatment of pain,” including “providing a patient [with renal impairment] with a therapeutically effective amount of oxymorphone.” Id. at 1350. The method “avoid[s] possible issues in dosing” and allows for treatment with “the lowest available dose” for patients with renal impairment. Id. However, the method to “avoid issues” involved assessing the patient’s creatinine clearance rate—a common general method to assess liver function. The claims were recited as follows:
[a] method of treating pain in a renally impaired patient.” ’737 patent col. 48 ll. 7–9. Claim 1 also requires specific steps: (a) providing a pharmaceutical (5–80 mg of oral controlled-release oxymorphone or one of its pharmaceutically acceptable salts), (b) testing the patient for a disease state (reduced kidney function based on creatinine clearance rate), and then (c) administering the pharmaceutical (a lower dose of oxymorphone) based on the creatinine clearance rate to achieve an average AUC of oxymorphone over a 12-hour period of less than 21 ng·hr/mL.
Id. at 1351 (citation omitted).
Essentially, the claim recites the application of dosage-based pharmacokinetics. Interestingly, the Endo court distinguished this test from another pharmacokinetic-type test case, in which an inventor used genetic testing to identify patients with metabolism issues and adjusted the dose accordingly to avoid the side effect of QTC prolongation (a well-known side effect in some psychotropic and quinolone drug classes). See Vanda Pharma. Inc. v. West-Ward Pharma. Int’l Ltd, 887 F.3d 1117 (Fed. Cir. 2018), petition for certiorari filed, Dec. 27, 2018 (No. 18-817). The court concluded that this claim was “directed to patent ineligible subject matter” because it was directed at a natural occurrence in the body and a response to a test, reversing the district court’s eligibility finding.
In summary, effective claims construction must elucidate the novel formula, normative data, or unique mathematical algorithm that allows greater sensitivity and specificity than currently exists in the art and in other tests on the market. This in turn would result not in the simple detection of a known reaction or predictor, but a more sensitive one, with a higher degree of accuracy, which allows for less frequent testing or less invasive modalities. Furthermore, objective differences in sensitivity and specificity should be supported with statistically significant findings. An expert, therefore, would elaborate on these statistically significant findings that transform the test from a simple “test positive” reaction of nature to a more effective means of diagnosis and treatment. More effective and nuanced use of experts at Markman hearings, with an eye toward explaining the novel transformative methods, may reverse the chilling effect of Mayo and its progeny.
Karen McKenzie, JD, RN, practices with the Judiciary of the Virgin Islands, Christiansted, Virgin Islands. She is also a member of the ABA Section of Litigation’s 2019–2021 Diverse Leaders Academy.
Copyright © 2020, American Bar Association. All rights reserved. This information or any portion thereof may not be copied or disseminated in any form or by any means or downloaded or stored in an electronic database or retrieval system without the express written consent of the American Bar Association. The views expressed in this article are those of the author(s) and do not necessarily reflect the positions or policies of the American Bar Association, the Section of Litigation, this committee, or the employer(s) of the author(s).