We remain bullish on the prospects for drug-drug interaction (“DDI”) patents to extend a drug’s exclusive life, particularly so long as FDA does not allow carve-outs of drug interaction infromation from generic labeling. Earlier this month, the Federal Circuit affirmed a PTAB decision that Teva Pharmaceuticals (“Teva”) had failed to prove invalid a DDI patent owned by Corcept Therapeutics (“Corcept”) for mifepristone (“Korlym®”), in Teva Pharm. United States v. Corcept Therapeutics, No. 2021-1360, 2021 U.S. App. LEXIS 36045 (Fed. Cir. Dec. 7, 2021).
The prior art disclosed that mifepristone, when administered by itself, should be administered at a starting dose of 300 mg/day, and gradually titrated up to as much as 1,200 mg/day. When administered with a strong CYP3A inhibitor, the prior art cautioned against administering more than 300 mg/day.
Corcept conducted a drug interaction study between mifepristone and ketoconazole (a strong CYP3A inhibitor) and, based on the results of that study, revised its FDA-approved prescribing information for Korlym® to recommend a dose of 600 mg when co-administered with ketoconazole. Corcept also secured a patent that effectively claimed this dosing regimen. The patent at issue, U.S. Patent No. 10,195,214, claimed:
A method of treating Cushing's syndrome in a patient who is taking an original once-daily dose of 1200 mg or 900 mg per day of mifepristone, comprising the steps of:
reducing the original once-daily dose to an adjusted once-daily dose of 600 mg mifepristone,
administering the adjusted once-daily dose of 600 mg mifepristone and a strong CYP3A inhibitor to the patient,
wherein said strong CYP3A inhibitor is selected from the group consisting of ketoconazole, itraconazole, nefazodone, ritonavir, nelfmavir, indinavir, boceprevir, clarithromycin, conivaptan, lopinavir, posaconazole, saquinavir, telaprevir, cobicistat, troleandomycin, tipranivir, paritaprevir, and voriconazole.
Crucial to the Federal Circuit's decision was a claim construction decision issued by the PTAB which limited claim 1 to the “safe” administration of mifepristone, even though the term “safe” appeared nowhere in the claim.
Teva argued that the 600 mg dose would have been obvious, but it could not present any evidence that mifepristone had ever been recommended at such a high dose when co-administered with ketaconazole, above the 300 mg dose cautioned against in the prior art. Given this lack of evidence, the PTAB held, and the Federal Circuit affirmed, that Teva failed to prove the “reasonable expectation of success” prong of obviousness. In particular, the PTAB held that Teva had not proven a reasonable expectation of safely administering 600 mg of mifepristone in combination with a strong CYP3A inhibitor. A person of ordinary skill in the art might have expected 600 mg of mifepristone to be effective against Cushing’s disease at this dose, but not for it to be safe.
Practice Pointer:
The case was won on a favorable claim construction that read a requirement for safety into a method of treatment claim, but practitioners should not count on such a fortunate construction. Practitioners would be well advised to specifically recite safety in the claims, particularly for inventions that rely on the dose of an active ingredient.
