Cleveland Clinic II: Has the Federal Circuit Undermined Patent Office Guidance and Eliminated an Important Tool for Patenting Diagnostics?

| Brenden S. Gingrich, Ph.D.

On April 1, 2019, the Federal Circuit issued a non-precedential decision in Cleveland Clinic Foundation, Cleveland HeartLab, Inc. v. True Health Diagnostics LLC (“Cleveland Clinic II”), affirming the district court’s holding that claim 1 of U.S. Patent No. 9,575,065 (the “ ’065 patent”) and claims 1 and 2 of U.S. Patent No. 9,581,597 (the “’597 patent”) were invalid under 35 U.S.C. § 101 as being directed to a patent-ineligible law of nature. In its decision, the Federal Circuit held that the courts are not bound by United States Patent and Trademark Office (USPTO) guidance, and concluded that a portion of the USPTO’s guidance on subject matter eligibility was inconsistent with controlling judicial precedent.

The ’065 and ’597 patents disclose “diagnostic test[s] which can be used to determine whether an individual . . . is at a lower risk or higher risk of developing or having cardiovascular disease.” ’065 patent, col. 1, ll. 21–25. The diagnostic tests are “based on the discovery that patients with coronary artery disease (CAD) have significantly greater levels of leukocyte and blood myeloperoxidase (MPO) levels.” Id. at col. 2, ll. 36–39. Claim 1 of the ’065 patent recites:

1. A method of detecting elevated MPO mass in a patient sample comprising:

a) obtaining a plasma sample from a human patient having atherosclerotic cardiovascular disease (CVD); and

b) detecting elevated MPO mass in said plasma sample, as compared to a control MPO mass level from the general population or apparently healthy subjects, by contacting said plasma sample with anti-MPO antibodies and detecting binding between MPO in said plasma sample and said anti-MPO antibodies.

In a prior decision in this dispute, Cleveland Clinic Foundation v. True Health Diagnostics LLC, 859 F.3d 1352 (Fed. Cir. 2017), cert. denied, 138 S. Ct. 2621 (2018) ("Cleveland Clinic I"), the Federal Circuit addressed the subject matter eligibility of a related patent, U.S. Patent No. 7,223,552 (the “’552 patent”). Claim 11 of the ’552 patent recites:

11. A method of assessing a test subject's risk of having atherosclerotic cardiovascular disease, comprising

comparing levels of myeloperoxidase in a bodily sample from the test subject with levels of myeloperoxidase in comparable bodily samples from control subjects diagnosed as not having the disease, said bodily sample being blood, serum, plasma, blood leukocytes selected from the group consisting of neutrophils, monocytes, sub-populations of neutrophils, and sub-populations of monocytes, or any combination thereo[f];

wherein the levels of myeloperoxidase in the bodily [samples] from the test subject relative to the levels of [m]yeloperoxidase in the comparable bodily samples from control subjects is indicative of the extent of the test subject's risk of having atherosclerotic cardiovascular disease.

In Cleveland Clinic I, the Federal Circuit held that the claimed method was invalid under § 101 as directed to the patent ineligible natural law; this natural law was the correlation of serum MPO levels with atherosclerotic cardiovascular disease (CVD), a correlation recited in the “wherein clause” of Claim 11.

On appeal in Cleveland Clinic II, the patentee argued that the claims of the ’065 and ’597 patents (unlike the claims in Cleveland Clinic I) were not directed to the natural law, but rather were directed to a technique of using an immunoassay to measure MPO levels of patients with atherosclerotic CVD. The alleged infringer, True Health, responded that the use of a known technique, in a standard way, to observe a natural phenomena, is insufficient to render the claims patentable under 35 U.S.C. § 101.

The Federal Circuit agreed with True Health, stating that “as we did in Cleveland Clinic I, [we conclude] that the claims are directed to the natural law that blood MPO levels correlate with atherosclerotic CVD.” The Federal Circuit explained that the distinction between the ’552 claims and the claims of the ’065 and ’597 patents was “overly superficial.” The Federal Circuit stated that the underlying natural law exists regardless of the methods used to observe it, and that the claims were not directed to any new technique of performing an immunoassay and, therefore, do not recite an inventive concept. The Court of Appeals concluded that “[t]he rephrasing of the claims does not make them less directed to a natural law.”

Cleveland Clinic also argued that the district court failed to give appropriate Skidmore deference to the subject matter eligibility guidance, recently published by the USPTO. Specifically, Cleveland Clinic argued that Example 29 of the USPTO guidance published on May 4, 2016, was applicable to the claims. Example 29 relates to detection of a hypothetical protein JUL-1 that naturally occurs in people with the autoimmune disease “julitis” but not in others. Claim 1 of Example 29 recites:

1. A method of detecting JUL-1 in a patient, said method comprising:

a. obtaining a plasma sample from a human patient; and

b. detecting whether JUL-1 is present in the plasma sample by contacting the plasma sample with an anti-JUL-1 antibody and detecting binding between JUL-1 and the antibody.

According to the USPTO guidance, this hypothetical Claim 1 would be patent eligible under § 101 because it is not directed at a natural law. In contrast, the USPTO guidance states that the same claim containing the additional step of “c. diagnosing the patient with julitis when the presence of JUL-1 in the plasma sample is detected,” would be patent ineligible because the additional step renders the claim directed to the patent ineligible natural law of a correlation between the presence of JUL-1 and the disease julitis.

The Federal Circuit rejected this argument, explaining that while the Court of Appeals greatly respects the USPTO’s expertise on matters relating to patentability, the USPTO’s guidance is not binding upon the Federal Circuit. Consistent application of its own case law was a more compelling mandate, and Claim 1 of Example 29 was strikingly similar to Claim 1 of U.S. Patent No. 6,258,540 (the “’540 patent”) which had been held ineligible in Ariosa:

1. A method for detecting a paternally inherited nucleic acid of fetal origin performed on a maternal serum or plasma sample from a pregnant female, which method comprises amplifying a paternally inherited nucleic acid from the serum or plasma sample and detecting the presence of a paternally inherited nucleic acid of fetal origin in the sample. Ariosa, 788 F.3d at 1373–74.

Claim 1 of the ’540 patent was ineligible because the techniques used for amplification and detection of paternally inherited cffDNA in maternal blood plasma were known in the art, similar to the conventional application of the techniques used to detect JUL-1. The Federal Circuit explained that neither Claim 1 of the ’540 patent nor Claim 1 of Example 29 from the USPTO guidance recite an inventive concept by reciting the discovery of the molecule’s presence in the sample. The Federal Circuit concluded that “to the extent that Example 29-Claim 1 is analogous to the claims at issue, Ariosa must control.”

It is important to note that this decision is non-precedential, and not binding on future Federal Circuit panels or other tribunals. Under the Federal Circuit’s Internal Operating Procedures, the choice to characterize this decision a non-precedential means that the Federal Circuit deems that this decision neither “add[s] significantly to the body of law,” nor establishes “a new rule of law.” See IOP No. 10(3) and 10(4)(c). Thus, this decision is unlikely to change the practice of examiners at the USPTO in allowing claims based on their similarity to Example 29-Claim 1. However, given the court’s decision, patent applicants should carefully consider whether to rely on Example 29-Claim 1 when prosecuting their patents.