Federal Circuit Holds That Claims Directed To A Specific Method Of Treatment For Specific Patients Using A Specific Compound At Specific Doses To Achieve A Specific Outcome Satisfy 35 U.S.C. §101

22nd April, 2019 - 1:07 pm Categories: Legal Issues 0 Comments

On March 28, 2019, the Court of Appeals for the Federal Circuit (CAFC) issued an opinion in Endo Pharmaceuticals Inc. v. Teva Pharmaceuticals USA, Inc., reversing a decision by the United States District Court for the District of Delaware in which the District Court had held the claims of U.S. Patent No. 8,808,737 to be ineligible under 35 U.S.C. § 101. The Federal Circuit ruled that Endo’s method of treatment claims were patent eligible under section 101 for claiming an application of a natural relationship and not the natural relationship itself.

Endo Pharmaceuticals owns the ‘737 patent, which pertains to a method of using oxymorphone in the treatment of pain by providing a patient with an oxymorphone dosage form and informing the patient or prescribing physician that the bioavailability of oxymorphone is increased in patients with renal impairment. The inventor of the ’737 patent studied the effect of renal impairment on the pharmacokinetics—including metabolism—of oxymorphone. Specifically, 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. Accordingly, the inventor’s treatment method advantageously allows patients with renal impairment to ingest less oxymorphone while still treating their pain. In technical terms, the inventor found that there was a statistically significant correlation between plasma AUC¹ for oxymorphone and a patient’s degree of renal impairment, as indicated by their creatinine clearance rate. Claim 1 of the ‘737 patent is representative and reads:

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.

Endo and Mallinckrodt LLC sued Actavis LLC, Actavis South Atlantic LLC, Actavis Pharma, Inc., Actavis Elizabeth LLC, Actavis Holdco U.S., Inc. (collectively, “Actavis”) and Teva Pharmaceuticals USA, Inc. and Barr Laboratories, Inc. (collectively, “Teva”) for allegedly infringing the ’737 patent’s claims 1−6. Actavis moved to dismiss Endo’s patent infringement claims, arguing that the patent claims were ineligible under § 101. The magistrate judge recommended granting Actavis’s motion. The magistrate judge first analyzed step 1 of the Alice/Mayo test (set forth in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 77 (2012), and reiterated in Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347 (2014)), reasoning that the claims are directed to the natural law that the bioavailability of oxymorphone is increased in people with severe renal impairment.

The magistrate judge then considered step 2 of the Alice/Mayo test, analyzing whether the ’737 patent claims, though directed to a law of nature, added enough to qualify as a patentable method that applies the law of nature. The magistrate judge separated claim 1 into three steps: (1) a “providing” step, (2) a “measuring” step, and (3) an “administering” step. First, the magistrate judge reasoned that the “providing” step is similar to the administering step in Mayo because it “merely identifies the specific drug for administration.” Second, the magistrate judge concluded that the measuring/determining step, like Mayo, “just directs one to use a well-known method to measure creatinine levels to obtain the necessary information to apply a law of nature.” Finally, the magistrate judge concluded that the “administering step” is indistinguishable from Mayo, because “[t]he administering step 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.”. Based on this analysis, the magistrate judge concluded that the ‘737 patent was not directed to a patent-eligible application of a natural law. The district court adopted the magistrate judge’s recommendation, finding the claims of ‘737 patent ineligible. Endo appealed the District Court’s decision.

The Federal Circuit noted that while the Supreme Court has established a two-step framework to determine subject matter eligibility under § 101, if the claims are not directed to a patent-ineligible concept at step one, the court need not address step two of the inquiry (citing Enfish, LLC v. Microsoft Corp., 822 F.3d 1327, 1339 (Fed. Cir. 2016)). The Federal Circuit determined that this was the case here, and accordingly focused solely on step one. The Federal Circuit noted that, at step one, “it is not enough to merely identify a patent-ineligible concept underlying the claim; we must determine whether that patent-ineligible concept is what the claim is ‘directed to.” (citing Rapid Litig. Mgmt. Ltd. v. CellzDirect, Inc., 827 F.3d 1042, 1050 (Fed. Cir. 2016)). Applying this law, the Federal Circuit concluded that the claims of ‘737 patent are not directed to patent-ineligible subject matter, but rather to a patent-eligible method of using oxymorphone or a pharmaceutically acceptable salt thereof to treat pain in a renally impaired patient. The Federal Circuit’s opinion said:

“Our conclusion is supported by the claim language itself and confirmed by the specification. The claims recite “[a] method of treating pain in a renally impaired patient.” ’737 patent col. 48 ll. 7–9. Claim 1 also requires specific steps: (a) providing a pharmaceutical (5–80 mg of oral controlled-release oxymorphone or one of its pharmaceutically acceptable salts), (b) testing the patient for a disease state (reduced kidney function based on creatinine clearance rate), and then (c) administering the pharmaceutical (a lower dose of oxymorphone) based on the creatinine clearance rate to achieve an average AUC of oxymorphone over a 12-hour period of less than 21 ng·hr/mL. Consistent with the claims, the abstract, patent title, and summary of the invention all describe the invention as a “method of treating pain” in patients with renal impairment. Id. at Abstract, col. 1 ll. 1–5; see id. at col. 2 ll. 35–43. The specification predominantly describes the invention as a method that treats renally impaired pain patients with less oxymorphone while still treating their pain. Indeed, the specification explains that the method “avoid[s] possible issues in dosing” and allows for treatment with “the lowest available dose” for patients with renal impairment.”

The Federal Circuit noted that it had held similar claims to be patent-eligible in Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals International Ltd, 887 F.3d 1117 (Fed. Cir.2018), and commented as follows:

“The claims at issue here are legally indistinguishable from the representative claim in Vanda. Both claims recite a method for treating a patient. The Vanda patent claims recite the steps of carrying out a dosage regimen based on the results of genetic testing. Here, the claims similarly recite the steps of carrying out a dosage regimen, though the steps are based on the results of kidney function testing. Additionally, the claims in both cases require specific treatment steps. In Vanda, the claims require doctors to “internally administer[] iloperidone to the patient in an amount of 12 mg/day or less” if the patient has a CYP2D6 poor metabolizer genotype; and “internally administer[] iloperidone to the patient in an amount that is greater than 12 mg/day, up to 24 mg/day” if the patient does not have a CYP2D6 poor metabolizer genotype. Id. (alterations in original) (quoting ’610 patent col. 17 ll. 13–20). Here, the claims require doctors to “orally administer[] to said patient, in dependence on which creatinine clearance rate is found, a lower dosage of the dosage form to provide pain relief” in such a way that after administering the dose, the patient’s “average AUC of oxymorphone over a 12-hour period is less than about 21 ng·hr/mL.” ’737 patent col. 48 ll. 7–26. 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.” See Vanda, 887 F.3d at 1136.”

The Federal Circuit also noted that like the claims in Vanda, the claims here differ from those in Mayo in material respects. The Court stated that 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, and that the administering step in Mayo is distinguishable from the administering step in the ’737 patent because the administering step in Mayo is the first step in the method that simply describes giving the drug to a patient with a certain disorder.

Actavis argued in the appeal proceedings that the court in Vanda emphasized the particularity of the claimed method’s “specific steps”—a specificity Actavis alleges is not found in the ’737 patent’s claims. According to Actavis, unlike the claims in Vanda, the method steps in Endo’s claims offer no “practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself.”. The Federal Circuit disagreed with Actavis, stating that the ’737 patent claims are very similar to those in Vanda and any differences in specificity are not of a sufficient degree to convince us to conclude that the claims here should be ineligible as compared to the claims in Vanda. In response to Actavis’s argument that unlike the Vanda claims, the ’737 patent claims do not require that a biological sample be obtained or assayed in any particular way to determine the patient’s creatinine-clearance rate, the Federal Circuit noted that this is a distinction without a difference as the court in Vanda reasoned that the claim was directed to “specific patients,” without explicitly emphasizing the precise methods used to identify those specific patients.

Actavis also argued that unlike Vanda, the ’737 patent’s claims do not specify an amount or frequency of oxymorphone to be administered after patients are categorized by creatinine-clearance rate. The Federal Circuit disagreed with Actavis’s interpretation of the claims in this regard, pointing out that “the wherein clause identifies the appropriate schedule and dose of oxymorphone to administer, as a function of how much oxymorphone is in the patient’s system”……and “the combination of the administering step and wherein clause claim language, taken together, that make the claims-at-issue as specific as those in Vanda such that the patent claims do not “tie up the doctor’s subsequent treatment decision.”. The Federal Circuit therefore concluded that the ’737 patent claims are like those in Vanda and 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.”

The Federal Circuit therefore found the ’737 patent claims patent-eligible under 35 U.S.C. § 101 and reversed the district court’s decision.

Author: Mr. Antony David, Principal Associate – Pharmaceutical-Life Sciences Practice Group at Khurana & Khurana, Advocates and IP Attorneys. In case of any queries please contact/write back to us at antony@khuranaandkhurana.com .