Renally Impaired Dosing Claims Eligible for Patent Protection

On March 28, 2019, the Federal Circuit Court of Appeals reversed a district court’s decision to dismiss Endo’s patent infringement lawsuit over its blockbuster drug Opana, finding that Endo’s claims for dosing oxymorphone in renally impaired patients were eligible for patent protection. Endo Pharm. Inc. v. Teva Pharm. USA, Inc., 919 F.3d 1347 (Fed. Cir. 2019).  

The claims at issue covered a method of treating paid in renally impaired patients by administering a smaller dose of oxymorphone than would normally be administered. Claim 1 recited:

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

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.

The district court had invalidated the patent under the Supreme Court’s Alice/Mayo framework, reasoning that the claims were directed to the natural law that the bioavailability of oxymorphone is increased in people with severe renal impairment.

The Federal Circuit reversed, likening the claims to the claims in Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals International Ltd, 887 F.3d 1117 (Fed. Cir. 2018), where the Federal Circuit held similar claims patent-eligible. The patent at issue in Vanda related to a method of treating schizophrenia patients with a drug (iloperidone), where the administered dose is adjusted based on whether or not the patient is a "CYP2D6 poor metabolizer." 

The Federal Circuit affirmed that the claims were eligible for patenting because “the inventor here recognized the relationship between oxymorphone and patients with renal impairment, but that is not what he claimed. Rather, 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.”

The lesson from the case is quite simple:  if a relationship between the bioavailability of the drug and the degree of renal impairment is not disclosed in the prior art, and a company conducts a renal impairment study, it might be able to secure a renal dosing patent.  Endo secured its patent even though the examiner initially argued that “It would be routine procedure for one of ordinary skill in this art at the time of the invention, to determine the amount of drug that would not overdose a renally-impaired patient and yet also provide relief from pain.” 

This patent related to an old drug, oxymorphone, that presumably had never been studied in renally impaired patients when Endo sought FDA approval for a new extended release dosage form.  However, the same opportunity arises with new molecules that have never been approved by FDA and are being investigated for the first time.