“Teva was required to prove a reasonable expectation of success in achieving the specific invention claimed, a 600 mg dosage.” – CAFC
The U.S. Court of Appeals for the Federal Circuit in a precedential decision yesterday affirmed a Patent Trial and Appeal Board (PTAB) decision that Teva Pharmaceuticals had failed to prove Corcept Therapuetics’ U.S. Patent No. 10,195,214 would have been obvious. The patent covers methods of treating Cushing’s syndrome, a disease caused by excessive levels of the naturally occurring steroid hormone, cortisol. Chief Judge Moore authored the opinion.
After Corcept sued Teva for infringement of the patent in district court, Teva petitioned the PTAB for post grant review of claims 1-13 of the ‘214 patent, arguing those claims would have been obvious over the prior art. The patent specifically relates to methods of treating Cushing’s syndrome by co-administering mifepristone and a strong Cytochrome P450 3A4 (CYP3A4) inhibitor. Representative claim 1 reads:
“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.”
Teva argued that the claims would have been obvious over the prior art or in combination with Food and Drug Administration guidance on drug-drug interaction studies. Teva’s expert testified that, based on the relevant prior art references, “it was reasonably likely that 600 mg [per day of mifepristone] would be well tolerated and therapeutically effective when co-administered with a strong CYP3A inhibitor.” But the PTAB found that statement inconsistent with the expert’s later testimony and other evidence in the record and found that Teva had failed to show that a skilled artisan would have had a reasonable expectation of success for safe co-administration of more than 300 mg of mifepristone with a strong CYP3A inhibitor.
Teva accused the PTAB of two legal errors: first, that it required “precise predictability” rather than a reasonable expectation of success in achieving he claimed invention; and second, that it found Teva had failed to prove the general working conditions disclosed in the prior art encompassed the claimed invention, instead of applying the CAFC’s prior-art-range precedents.
In addressing the first alleged legal error, the court said the Board had not erred in requiring Teva to show a reasonable expectation of success for a specific dosage, since the relevant claim refers to a specific dosage. “Thus, the Board was required to frame its reasonable-expectation-of-success analysis around that specific dosage of mifepristone,” wrote the CAFC. The decision continued:
To be clear, this does not mean Teva was required to prove a skilled artisan would have precisely predicted safe co-administration of 600 mg of mifepristone. Absolute predictability is not required. See, e.g., Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007). But Teva was required to prove a reasonable expectation of success in
achieving the specific invention claimed, a 600 mg dosage.
The court concluded that nothing about the Board’s analysis “required precise predictability, only a reasonable expectation of success tied to the claimed invention.”
As to Teva’s expert, Dr. Greenblatt, although he testified prior to institution “it was reasonably likely that 600 mg [per day of mifepristone] would be well tolerated and therapeutically effective when co-administered with a strong CYP3A inhibitor,” he later testified that skilled artisan “would have no expectation as to whether the co-administration of 600 mg of mifepristone with ketoconazole would be safe.” The latter testimony was consistent with several other statements Greenblatt had made, and the Board thus discredited the former statement.
Turning to the prior-art-range precedent, the CAFC said that substantial evidence supported the Board’s finding that “the general working conditions disclosed in the prior art” did not point to overlap between the claimed ranges and the ranges disclosed in the prior art. Specifically, the Board held that “the evidence of record support[ed] that the general working conditions limited co-administration of mifepristone with a strong CYP3A inhibitor to just 300 mg/day.”
Thus, while Teva described this as an “uncommonly clear-cut obviousness case,” the court held that Teva ignored the reasonable-expectation-of- success requirement, showing only that the prior art may have directed a skilled artisan to combine the references, without demonstrating a reasonable expectation of success in doing so, which is necessary to prove obviousness.