Written by Marc Chatenay-Lapointe, Ph.D. and Agnes Juang, Ph.D.

The recent district court ruling in INO Therapeutics LLC et al v. Praxair Distribution, Inc. et al employed the two-step analytical framework of Mayo/Alice to evaluate subject matter eligibility under 35 U.S.C. § 101, and the court found U.S. Patent Nos. 8,795,741 (“’741 patent”), 8,282,966, 8,293,284, 8,431,163, and 8,846,112 (collectively, the "HF patents") to be invalid.

The challenged HF patents are listed in the Orange Book for Mallinckrodt’s drug INOMAX® (nitric oxide). Claim 1 of the ’741 patent, which according to the court is the exemplary claim for the HF patents, reads as follows:

A method of treating patients who are candidates for inhaled nitric oxide treatment, which method reduces the risk that inhalation of nitric oxide gas will induce an increase in pulmonary capillary wedge pressure (PCWP) leading to pulmonary edema in neonatal patients with hypoxic respiratory failure, the method comprising:

(a) identifying a plurality of term or near-term neonatal patients who have hypoxic respiratory failure and are candidates for 20 ppm inhaled nitric oxide treatment;
(b) determining that a first patient of the plurality does not have left ventricular dysfunction;
(c) determining that a second patient of the plurality has left ventricular dysfunction, so is at particular risk of increased PCWP leading to pulmonary edema upon treatment with inhaled nitric oxide;
(d) administering 20 ppm inhaled nitric oxide treatment to the first patient; and
(e) excluding the second patient from treatment with inhaled nitric oxide, based on the determination that the second patient has left ventricular dysfunction, so is at particular risk of increased PCWP leading to pulmonary edema upon treatment with inhaled nitric oxide.

Applying the two part test set forth in Mayo/Alice, the court first determined that the HF patent claims were directed to natural phenomena. Both the Plaintiffs' and Defendants' experts agreed that “iNO's [(inhaled nitric oxide’s)] effect on a neonate with LVD [(left ventricular dysfunction)] was a matter of human physiology.” INO Therapeutics LLC et al v. Praxair Distribution, Inc. et al, 1-15-cv-00170, at 22 (DED September 5, 2017). However, the Plaintiffs argued that “the discovery in the [HF patent inventor’s] INT022 study that neonates with LVD that were treated with iNO were at an increased risk of pulmonary edema – was ‘much more probabilistic than deterministic.’” Id. (emphasis added). The court rejected the argument that this conclusion meant it was not a natural phenomenon, reasoning that “[w]hether the phenomenon occurs in some patients, as opposed to all patients, does not change the physiological reasons for its occurrence.” Id. at 23. The court also found parallels between the claims at issue and the invalidated Mayo claims. The Mayo claims were directed to a method of determining the likelihood that a dosage of a thiopurine drug will prove ineffective or cause harm, which comprise the steps of "(1) 'administering a [thiopurine] drug' to a patient and (2) 'determining the [resulting metabolite] level." Id. The court found that “[h]ere, just like in Mayo, some of the claimed steps require human action. Nonetheless, the core of the alleged invention… is really a patient populations' natural physiological response to [treatment].” Id.

Moving to step two of the Mayo/Alice framework, the court examined the claim limitations, both individually and as an ordered combination, to determine if they contained an inventive concept sufficient to transform the claimed phenomena of nature into a patent-eligible application. Id. at 24. The court found that the first “identifying” step, the second and third “determining” steps, and the fourth “administering” step were routine and conventional in the art based on disclosures in the specification. Id. at 24-25. The Plaintiffs argued that the fifth “excluding” step transformed the claim into patent-eligible subject matter, as “[n]one of the clinical trials (other than the revised INOT22 protocol) excluded neonates or children with LVD from iNO therapy prior to the critical date, underscoring that the methods involve a new use for iNO.” Id. at 25. The court rejected this argument, noting that "even valuable contributions [to science] can fall short of statutory patentable subject matter." (citing Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F . 3d 1371, 1380 (Fed. Cir. 2015)). The court again analogized to Mayo, holding that the claimed method simply tells the relevant audience about the natural phenomenon and directs that audience to take that phenomenon into account when treating patients. The court further reasoned that “Plaintiffs cannot seriously contend that it is a new practice to exclude certain patients from treatment with a drug when those patients are at an increased risk of experiencing negative side effects from the drug.” Id. at 26. The remaining claim elements found in the other claims of the ’741 patent or other HF patents were not found to supply an inventive concept, as the court argued that the additional limitations were inherently necessary to treatment with iNO (e.g., “supplying the cylinder containing the compressed nitric oxide gas to a medical provider...”) or routine and conventional in the art (e.g., “performing echocardiography”). For these reasons, the court found the claims of the HF patents recite patent-ineligible subject matter.