In Endo Pharmaceuticals Inc. v. Teva Pharmaceuticals USA, Inc., the Federal Circuit distinguished method of treatment claims that involve personalized dosing from the claims invalidated in Mayo v. Prometheus, and found them to satisfy 35 USC 101 by analogy to Vanda. The district court had invalidated the method of treatment claims at the motion to dismiss stage of ANDA litigation.

The Endo Opana Patent At Issue

The patent at issue was U.S. Patent No. 8,808,737, which is listed in the Orange Book for Endo’s Opana ER® (oxymorphone hydrochloride) product. As summarized in the Federal Circuit decision, “the inventor discovered that patients with moderately or severely impaired kidney function need less oxymorphone than usual to achieve a similar level of pain management.” Thus, “the inventor developed a method that allowed renally impaired pain patients to be treated safely and effectively notwithstanding their impaired kidney function.”

The court treated claim 1 as representative:

1. A method of treating pain in a renally impaired patient, comprising the steps of:
a. providing a solid oral controlled release dosage form, comprising:
i. about 5 mg to about 80 mg of oxymorphone or a pharmaceutically acceptable salt thereof as the sole active ingredient; and
ii. a controlled release matrix;
b. measuring a creatinine clearance rate of the patient and determining it to be
(a) less than about 30 ml/min,
(b) about 30 mL/min to about 50 mL/min,
(c) about 51 mL/min to about 80 mL/min, or
(d) above about 80 mL/min; and
c. 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.

Quoting from the patent, the court noted:

[T]he inventor found that there was a statistically significant correlation between plasma AUC for oxymorphone and a patient’s degree of renal impairment, as indicated by their creatinine clearance rate. …. Because of this, the oxymorphone levels in the blood of a patient with [] renal impairment are higher than the levels that would be seen in a healthy patient receiving the same dose.”

The district court invalidated the claims based on the magistrate judge’s Alice/Mayo analysis. At step 1, the claims were determined to be “directed to the natural law that the bioavailability of oxymorphone is increased in people with severe renal impairment.” At step 2, the “administering” step was found to be similar to that at issue in Mayo, as it “merely instructs physicians to dispense oxymorphone for the treatment of pain in a well-know[n] manner, while utilizing the natural law to manage the dosage.”

As noted by the Federal Circuit, the district court decision was rendered before the Federal Circuit upheld personalized method of treatment claims in Vanda.

The Federal Circuit Decision

The Federal Circuit decision was authored by Judge Stoll and jointed by Judges Wallach and Clevenger.

The Federal Circuit focused on step one of the Alice/Mayo analysis, and determined that the claims were not “directed to” a law of nature. The court emphasized:

If the claims are not directed to a patent-ineligible concept at step one, we need not address step two of the inquiry.

This is similar to the USPTO examination guidance issued after Vanda, which generally provides that methods of treatment can and should be found to satisfy 35 USC 101 at step one of an Alice/Mayo analysis (which corresponds to Step 2a of the USPTO’s analytical framework.)

Turning to the claims before it, the Federal Circuit found:

[T]he claims are directed to a patent-eligible method of using oxymorphone or a pharmaceutically acceptable salt thereof to treat pain in a renally impaired patient. Our conclusion is supported by the claim language itself and confirmed by the specification.

The court explained further:

The claims at issue here are legally indistinguishable from the representative claim in Vanda. Both claims recite a method for treating a patient. …. Additionally, the claims in both cases require specific treatment steps. Like the claims in Vanda, the claims here “are directed to a specific method of treatment for specific patients using a specific compound at specific doses to achieve a specific outcome.”

In that regard, the court found that “the wherein clause requires that the dosage and schedule administered in the ‘orally administering step’ must achieve a target average AUC of oxymorphone less than about 21 ng·hr/mL over a 12-hour period.”

As it did in Vanda and Natural Alternatives, the court distinguished the claims from those at issue in Mayo. 

Although the representative claim in Mayo recited administering a thiopurine drug to a patient, the claim as a whole was not directed to the application of a drug to treat a particular disease.

The Federal Circuit acknowledged that “the inventor here recognized the relationship between oxymorphone and patients with renal impairment,” but emphasized “that is not what he claimed.” Instead, “he 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.”

Is This What It Takes?

The Federal Circuit opinion includes this conclusion:

At bottom, we conclude that the ’737 patent claims are like those in Vanda. They are eligible because they are “directed to a specific method of treatment for specific patients using a specific compound at specific doses to achieve a specific outcome.” …. Our precedent leaves no room for a different outcome.

While I do not disagree that method of treatment claims should satisfy 35 USC 101, I do question whether a method of treatment claim needs to recite a specific method of treatment for specific patients using a specific compound at specific doses to achieve a specific outcome in order to satisfy the statute.

Also notable here is the court’s lengthy discussion of the inventor’s discoveries, how the claimed methods were based on those discoveries, and how the claimed methods offer improved treatment outcomes. While it is possible that the discussion sheds light on how the court reached its decision, I prefer to think it is designed to reassure the Supreme Court that the decision is the correct one.