In Endo v. Teva, Appeal 2017-1240 (Fed. Cir., March 19, 2019), a Fed. Cir. panel of Judges Stoll, Wallach and Clevenger unanimously found patent-eligible claims to a method of treating pain with oxymorphone, based on the inventor’s discovery that there was a significant correlation between plasma AUC for the drug and a patient’s degree of renal impairment (U.S. Pat. No. 8,808,737). As Judge Stoll wrote:

“[U.S. Pat. No. 8,808,737] relates to his discovery that patients with renal impairment in need of pain relief can be treated in a new different way than other patients. Specifically, the inventor discovered than patients with moderately or severely impaired kidney function [as measured by creatinine clearance levels] need less oxymorphone than usual to achieve a similar level of pain management” [emphasis added].

The claim is not a model of elegant drafting, but it got the job done:

1. A method of treating pain in a renally impaired patient, comprising the steps of:

   1. Providing a solid oral controlled release dosage form, comprising:

      1. About 5 mg to about 80 mg of oxymorphone or a pharmaceutically acceptable salt thereof as the sole active ingredient and

      2. A controlled release matrix;

   2. Measuring a creatinine clearance rate of the patient and determining it to be [within one of four ranges representing renal impairment from healthy control to severe renal impairment; and

   3. Orally administering to said patient, in dependence on which creatinine clearance rate is found, a lower dosage of the dosage form to provide pain relief;

Wherein after said administration to said patient the average AUC of oxymorphone over a 12-hour period is less than about 21 ng hr/ml. [emphasis added].

The district court adopted the findings of the magistrate judge, finding that the natural law is that the bioavailability of oxymorphone is increased in people with severe renal impairment and, considering the Mayo claims, that “[t]he administering step merely instructs physicians to dispense oxymorphone for the treatment of pain in a well-known manner, while utilizing the natural law to manage the dosage.” Considering that the claim was otherwise indistinguishable from the Mayo claim, the district court concluded that the patent was not directed to a patent- eligible application of a law of nature.

Noting that the district court decision preceded Vanda v. West-Ward, the panel held that claim 1 (above) is directed to a method of treating pain in subjects with renal impairment that are legally indistinguishable from the claims at issue in Vanda: “Like the claims in Vanda, the claims here ‘are directed to specific method of treatment for specific patients using a specific compound at specific doses to achieve a specific outcome’…Although the representative claim in Mayo recited administering a thiopurine drug to a patient [ed. note: I think that the Mayo claim said “subject”], the claim as a whole was not directed to the application of a drug to treat a particular disease.”

The panel distinguished the administering step in Mayo from the administration step 1, above, and cited the Supreme Court’s dictum in Mayo that the claim at issue was “[u]nlike, say, a typical patent on a new drug or a new way of using an existing drug, the [Mayo claims] do not confine their reach to particular applications of those [natural] laws.” The panel noted the in vivo correlation present in both the Vanda claims and the present claims, “but that is not what [the inventor[s]] claimed. Rather, they claimed an application of that relationship—specifically, a method of treatment including specific steps to adjust or lower the oxymorphone dose for patients with renal impairment. The claims are thus directed to more than just reciting the natural relationship” [emphasis added].

Well, fair enough, but the Fed. Cir. still needs to adequately explain why discovery of previously unknown in vivo correlation or “relationship” that leads to a diagnostic conclusion that forms in the mind of the researcher who elucidated the utility of the correlation is not more “than just reciting the natural relationship.” Why did the Fed. Cir., e.g., in Athena v. Mayo, rule that the “detecting step” is not “more than just reciting the natural relationship”? In Athena, “[t]he named inventors …discovered that many of the 20% of MG patients without acetylcholine receptor autoantibodies instead generate autoantibodies to a membrane protein called MuSK.” They claimed: “A method for diagnosing neurotransmission…disorders related to [MuSK] in a mammal comprising the step of detecting in a bodily fluid of said mammal autoantibodies to an epitope of [MuSK].” Patent-ineligible. Next.

Why isn’t this recognition step a practical application of the natural phenomenon? In Athena, the court jumped strait from a finding that the binding of MuSK to MuSK antibodies is a law of nature to step 2B of the Mayo/Alice test, and you know how that comes out.   The only explanation that I can come up with is that the judicially unsound “principle” that mental steps in a claim can be disregarded when determining patentability has somehow been imported into the Mayo/Alice test. Unintentionally, but worse yet, the most recent PTO guidance reminds us that claims directed to mental steps are impermissible attempts to claim abstract ideas, but this has nothing to do with the mental activity employed in applying a natural correlation to arrive at a useful, even life-saving, conclusion. Once the mental steps recited in a claim to a diagnostic method are ignored, the patentee is left to argue that the manipulative sampling/assaying steps add the additional “inventive step” required by the Mayo/Alice test step 2B. That has never been successful.

In Athena, the panel wrote: “laws of nature are not patentable, but applications of such laws may be patentable. A claim to otherwise statutory subject matter [such as a process] does not become ineligible by its use of a law of nature” [citing Diehr]. But then the panel jumped straight into the requirement that the other claim limitations must “ensure that the patent in practice amounts to significantly more than a patent upon the natural law itself.” The “significantly more” language is from Mayo, but what Supreme Court decision forces the Fed. Cir. to require that the “significantly more” requirement be met solely by requiring that the claim contain the elusive “inventive step” of step 2B of the Mayo/Alice test?

Why shouldn’t a claim reciting a natural phenomenon first be evaluated to see if the claim is directed to a practical application of the phenomenon? The recent PTO Guidance is intended to prevent that legal shortcut to step 2B in the case of claims that recite abstract ideas, but I think the Guidance should be expanded to include “practical applications” of natural phenomenon.