In 2011 the Supreme Court announced that methods of diagnosing disease are ineligible for patenting under its landmark decision, Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66 (2011). The decision, authored by Justice Stephen Breyer, reasoned that measuring the concentration of a biomarker (in that case a drug metabolite) and diagnosing a patient as either overdosed or under-dosed is nothing more than making a decision based on a natural law. This was the first of three major Supreme Court decisions remaking U.S. patent law to exclude many forms of biotechnology and information technology (the other two being Association for Molecular Pathology v. Myriad Genetics, 133 S.Ct. 2107 (2013) and Alice Corp. v. CLS Bank Int’l, 134 S.Ct. 2347 (2014)). A recent decision by a federal district court, Mallinckrodt Hospital Products IP Ltd. et al. v. Praxair Distribution, Inc., Case No. 15-170-GMS (D. Del., Sep. 5, 2017), imposed new restrictions on how these decisions are applied to diagnostic methods.

The Alice Test for Patent Eligibility

The current test for subject matter eligibility under these decisions (as restated in Alice) has been described as a two-part test, but in fact the test has three distinct parts. The first step is to determine whether the claim is one of the categories of subject matter Congress intended should be patented, as expressed in 35 U.S.C. § 101: “any new and useful process, machine, manufacture, or composition of matter, or new and useful improvement thereof” (the “statutory categories”). If the first answer is “no,” then the claim is not eligible subject matter. If the first answer is “yes,” the second step is to determine whether the claim is “directed to” one of the judge-made exceptions to the statutory categories: an abstract idea, a physical phenomenon, or a law of nature. If the second answer is “no,” then the claim is eligible. If the second answer is “yes,” then the third step is to determine whether the claim as a whole encompasses “substantially more” than the judicial exception itself. Finally, if the answer to the third step is “yes,” then the claim is patent eligible; if it is “no,” then the claim is not patent eligible.

Treatment Based on Diagnosis Prior to Mallinckrodt

Decisions following Mayo generally concluded that an invention involving the diagnosis of a disease is eligible for patenting if it involves another unconventional step, such as administering a course of medication based on the diagnostic step. A treatment step is considered to add “substantially more” to the claim, particularly when the treatment depends on the diagnosis. Such decisions follow the Federal Circuit’s decision in Classen Immunotherapies, Inc. v. Biogen Idec, 659 F.3d 1057 (Fed. Cir. 2011). In Classen the invention was a method of designing a schedule of immunizations to reduce the occurrence of side effects, coupled with administering the immunizations according to the schedule. Because immunizing patients is a concrete step, and because following the inventive schedule was neither conventional nor well-understood, the court decided that it added “substantially more” to the claim than just the understanding of the natural law underlying the relationship between the immunization schedule and the side effects.

The Classen rule is followed by the USPTO, which incorporated a similar example in its official guidance on subject matter eligibility (Subject Matter Eligibility Examples: Life Sciences, May 4, 2016), and cites Classen in its patent examiner’s manual (see MPEP 2106.05(e), inter alia). In Example 19 of the Life Sciences Examples, a hypothetical claim is presented for performing a diagnostic test that distinguishes between two frequently confused diseases (julitis and rosacea) followed by administering a treatment for julitis (that is ineffective against rosacea) if the biomarker is present. The public has of course relied upon the Classen decision, the MPEP, and the USPTO’s guidance in evaluating whether diagnostic technologies can be patented.

In a later decision by the Federal Circuit, claims for diagnosis alone were held ineligible, but the patent eligibility for accompanying claims for treatment based on a diagnosis were not even challenged by the accused infringer. See Cleveland Clinic Foundation v. True Health Diagnostics LLC, Case No. 2016-1766 (Fed. Cir., June 16 2017).

The Conflicting Mallinckrodt Decision

In a departure from the previous trend, a district court judge in the Federal District Court of Delaware (one of the more influential patent venues) held that diagnosing a disease followed by treating the disease based on the diagnosis is not eligible for patenting.

In Mallinckrodt, the district court considered claims to a method of treating hypoxia in newborns with nitric oxide while reducing the risk of a deadly side effect, pulmonary edema. 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 included claims to diagnosing a hypoxic infant for left ventricular dysfunction by echocardiography, and administering an appropriate concentration of nitric oxide only in the absence of left ventricular dysfunction. As in Classen, 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.

The trial court found that the connection between left ventricular dysfunction and an infant’s vulnerability to pulmonary edema when given nitric oxide is an ineligible law of nature, and that administering nitric oxide only when left ventricular dysfunction is absent is not “substantially more” than recognizing the connection, because nitric oxide is a conventional and well-understood treatment for hypoxia. The court found that echocardiography as the method of detecting left ventricular dysfunction did not add “substantially more” to the claim, either, because echocardiography was also a conventional and well-understood way to detect left ventricular dysfunction.

Oddly, the court in Mallinckrodt neither cited nor considered Classen. Although it cited Cleveland Clinic, the important distinction between the claims that included the treatment step and those with only the diagnosis step was not discussed or even recognized. This decision then appears to conflict with Classen, and without any analysis of Classen in Mallinckrodt it can only be guessed why the two decisions diverge (apart from the usual lack of judicial consistency when it comes to patent eligibility). In Classen the immunizations, while claimed at a high level of generality, were administered according to a new and unconventional schedule. In Mallinckrodt, a known treatment (nitric oxide) was claimed to be withheld from a certain population of patients, which was new and unconventional. In both cases the drugs themselves were well-known, but the pattern of whether and when to administer the drugs was not. One distinction between the inventions in these cases is that Mallinckrodt involved a binary decision to “administer or not administer” the drug, while Classen involved chronologically scheduling the administration of the drug. If the lesson of Mallinckrodt is that providing or withholding a given treatment based on a diagnosis is not “significantly more” than the treatment itself, then it conflicts with the USPTO’s public guidance in the MPEP and the Life Sciences Examples.

Does Mallinckrodt Change Anything?

The trial court’s decision has been appealed to the U.S. Court of Appeals for the Federal Circuit, which is the appeals court with jurisdiction over all patent appeals. If the Federal Circuit adopts Mallinckrodt and abandons Classen, it will deal another significant blow to those developing advanced diagnostic methods. At the very least it would call into question the settled understanding of the public (and the officials at the USPTO) that methods of treatment tied to methods of diagnosis can still be patented. However, even if the decision in Mallinckrodt is affirmed, planning the funeral for American diagnostic patents may be premature. For those who value predictability in the application of the law, it may be hoped that the Federal Circuit will either reverse the decision in Mallinckrodt, or somehow reconcile these cases.