As discussed in a previous blog post, since Mayo v. Prometheus, critics of medical treatment patents have advocated that such patents should be banned from patenting. While such arguments seemed futile based on the consistent position taken by the U.S. Court of Appeals for the Federal Circuit (CAFC) that treating a disease or other condition is not merely a “mental process” or “natural law,” the CAFC’s recent decision in INO Therapeutics, LLC v. Praxair Distribution Inc. may have changed that. Indeed, if this decision is followed by other panels of the CAFC, it could have a profound effect on the patenting of personalized medicine in the United States.

The Old Rule: Medical Treatment Informed by Diagnostic Testing Could be Patented

Prior to INO, the CAFC consistently ruled that methods of medical treatment are patent-eligible subject matter, regardless of whether they are combined with a diagnostic step. In Classen Immunotherapies Inc. v. Biogen IDEC – the seminal case in this line – the CAFC considered the patent eligibility of a claimed method of immunization of a subject that involved first immunizing a number of other subjects according to two immunization schedules and determining which has the least risk of side effects, then immunizing the subject according to the schedule with the lowest risk.

The unanimous panel found the act of immunizing two groups of subjects and comparing the results to determine the best immunization schedule, without applying that schedule to a subject, not eligible for patenting. However, with the extra step of actually immunizing a subject based on the schedule, the majority of the panel held that the claimed method was patent eligible. Notably, while the majority held that a method of medical treatment is eligible for patenting, even if it involves mental steps, a dissenting judge thought the claims were “a monopoly over the scientific method itself.” The CAFC followed this analysis in several later decisions, including in Natural Alternatives International, Inc. v. Creative Compounds, LLC; Endo Pharmaceuticals Inc. v. Mallinckrodt, LLC; and Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals Int’l Ltd.

In contrast, the CAFC has consistently found patent claims that include only diagnostic steps, without any form of medical treatment, ineligible for patenting. Such cases include Myriad (by the Federal Circuit, before it went to the Supreme Court); PerkinElmer Inc v. Intema Ltd.; Univ. of Utah Research Foundation v. Ambry Genetics Corp.; Cleveland Clinic Foundation v. True Health Diagnostics, LLC; Roche Molecular Systems, Inc. v Cepheid; and Ariosa Diagnostics, Inc. v. Sequenom, Inc.

The INO Rule: Withholding Treatment Dooms the Patent

The invention claimed in INO was directed to a method of treating hypoxia in newborns with nitric oxide while reducing the risk of pulmonary edema (a deadly side effect). The inventors discovered that infants with impaired function of the left ventricle are at elevated risk for pulmonary edema if treated with nitric oxide. The asserted claims of the patents in suit featured a method of diagnosing a hypoxic infant for left ventricular dysfunction (LVD) by echocardiography and administering an appropriate concentration of nitric oxide only in the absence of left ventricular dysfunction.

As in Classen and its progeny, the claims involved a medical intervention based on the result of the diagnostic step. Unlike Classen, the trial court in Mallinckrodt held that the use of previously known treatment methods based on the diagnosis does not add “significantly more” to the understanding of the natural law. You can read more about the trial court decision here.

Two of the three judges on the CAFC panel agreed with the trial court. The majority felt that invention in INO was different from those in Classen, Endo, Natural Alternatives, and Vanda in one significant way: in INO, the diagnostic step determined to which patients nitric oxide should be administered and to which patients it should be withheld, whereas in the other decisions, treatment was administered in some form, although the form differed depending on the results of the test.

The majority cited numerous, separate reasons that the distinction caused the invention to fall under the Mayo/Myriad ban. First, the majority explained that “[t]he effect of [nitric oxide] gas on a newborn with LVD is a matter of human physiology.” The majority then stressed that the use of nitric oxide was not new and, therefore, “the patented method does not propose a new way of treating LVD patients.” Although the patentee argued that the claim in its entirety was new, the majority dismissed this “whole claim” approach, opining that “…the focus of the invention is screening for a particular adverse condition that, once identified, requires iNO treatment be withheld.”

The majority contrasted this case with Vanda and Endo, because in the latter cases, the diagnostic test determined the dosage at which a specific treatment is given. Because treatment is administered regardless of the test results, the majority believes these are properly interpreted to be “methods of treatment.” The INO invention, on the other hand, involves either administration of a specific drug at a specific dosage or non-administration of that drug.

It would seem that the majority’s decision is based on the premise that (1) the claimed treatment with nitric oxide of infants without LVD cannot be considered in the patent eligibility analysis because nitric oxide treatment was already known and (2) the claimed withholding of nitric oxide treatment of infants with LVD is not really a method of treatment because no treatment is administered. In fact, the majority explained that a claim not to treat is akin to not disturbing the naturally occurring processes within the LVD patient’s body and “risks monopolizing the natural processes themselves.” Therefore, the claimed method is merely “instruction” to apply the “law of nature” of how nitric oxide affects human physiology.

Judge Newman – the most senior judge on the CAFC – dissented. Her dissenting opinion took a familiar direction, pointing out that the claimed invention was not a “law of nature” as “it was designed by and is administered by humans.” She further pointed out that all medical treatments rely on the response of human physiology to an artificial intervention. She finally pointed out that the Supreme Court has repeatedly cautioned against dissecting claims into component parts and considering only specific parts in the patent eligibility analysis. As noted by Judge Newman in her dissent, while the claimed method may in fact be invalid under the tests of novelty or obviousness, to declare it patent-ineligible is contrary to preceding decisions from the Supreme Court and the CAFC.

Where Does this Leave Personalized Medicine?

This decision leaves many key questions about patent eligibility unanswered and the future uncertain for personalized medicine patents. Prior to INO, the Vanda decision was regarded as a beacon in the foggy post-Mayo world when it came to patenting personalized medicine. It introduced an unaccustomed level of certainty to the question of subject matter eligibility since Mayo. In fact, published USPTO guidance relies on Vanda to teach that “it is not necessary for method of treatment claims that practically apply natural relationships to include nonroutine or unconventional steps to be considered patent eligible under 35 U.S.C. § 101.”

INO calls all of that into question for a number of reasons. First, the majority did not explain why the Mayo/Myriad ban applies to treatment regimens where a treatment is completely contraindicated by test results but not to regimens where the dosage is changed.

Second, the majority opined that Vanda claimed “an improved set of specific doses” but that INO did not. But in Vanda, the lower dosage in the claim was not more effective to treat the disorder; rather, it had less side effects. This appears to be eerily similar to the claims in INO, except that the INO claims effectively require a “zero dosage” for infants with LVD.

Third, the majority gives no explanation of the relevance of the fact that the use of nitric oxide without reference to LVD was already known. Indeed, the treatment steps in Vanda and Endo were also already known if severed from the diagnostic steps.

In summary, although the majority opinion repeatedly attests that there is no inconsistency between INO and the CAFC’s previous opinions, INO seems to be at odds with established precedent and appears to signal another period of uncertainty and inconsistency regarding the patentability of personalized medicine in the United States. Inventors of personalized medicine inventions would be wise to consider maintaining their innovations as a trade secret or explore markets outside of the United States to protect their inventions.