There are some cases where the Federal Circuit makes its decision based on the eternal verities of patent law (insofar as there are any eternal verities in patent law). One such decision arose earlier this month when the Federal Circuit affirmed a determination of non-obviousness by the Patent Trial and Appeal Board in an inter partes review proceeding, that opinion captioned Teva Pharmaceuticals USA, Inc. v. Corcept Therapeutics, Inc.
The case arose incident to ANDA litigation between the parties involving Corcept's Korlym product comprising the active pharmaceutical ingredient mifepristone for treating Cushing's Syndrome. The drug had been recognized since the 1980's as an antiprogestin compound, but its relevant effect in vivo turned out to be as a glucocorticoid reception antagonist, which suggested its use against Cushing's (which was known to be caused by excessive levels of cortisol). Corcept obtained FDA approval for the drug contingent on its performance of a post-marketing study under the provisions of 21 U.S.C. § 355(o)(3), one of which was to conduct "[a] drug-drug interaction clinical trial to determine a quantitative estimate of the change in exposure of mifepristone following co-administration of ketoconazole (a strong CYP3A4 inhibitor)." The agency provided a description of the basis for this study, which included information such as ignorance in the art regarding the "degree of change" in exposure to mifepristone in the presence of drugs like ketoconazole and the potential safety risk that could arise. Important to the issues before the Court was Korlym's approved label, which recommended a starting dose of 300 mg/day that could be increased in increments to 1200 mg/day, and a caveat that administration of the drug should be limited to 300 ng/day in the presence of strong CYP3A inhibitors.
Corcept performed the required study and obtained patent protection on the resulting treatment method, U.S. Patent No. 10,195,214; claim 1 is representative:
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.
The basis for Teva's IPR challenge was that this claim was obvious over Korlym's label in combination with the FDA study memorandum (which the opinion refers to as "Lee"), further and optionally in combination with FDA guidance documents on drug-drug interactions.
The Board found that Teva had not satisfied its burden of showing obviousness by a preponderance of the evidence, specifically a showing 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." The Board's decision also specifically discredited Teva's expert's declaration and testimony to the contrary. This appeal followed.
The Federal Circuit affirmed, in a decision by Chief Judge Moore joined by Judges Newman and Reyna. The opinion sets forth the bases for Teva's appeal as first, that the Board required "precise predictability" from the prior art in achieving the claimed invention (instead of a reasonable expectation of success) and second, that the issue involved "range" precedents that the Board did not apply (for recent examples, see Biogen Int'l GmbH v. Mylan Pharmaceuticals Inc. (Fed. Cir. 2021), and Indivior UK Ltd. v. Dr. Reddy's Laboratories S.A. (Fed. Cir. 2021)). As can be her wont, the Chief Judge summarized the panel's opinion in the simple phrase "[w]e do not agree" with either of these arguments.
With regard to the "reasonable expectation of success" argument, the opinion notes that the existence of the expectation is a question of fact requiring substantial evidence (although noting that the ultimate obviousness determination is a question of law subject to de novo review). The issue, according to the Federal Circuit, was whether the skilled artisan would have had a reasonable expectation of success in achieving the invention as claimed with regard to the specific mifepristone dose (600 mg/day) in combination with a strong CYP3A inhibitor. What the skilled worker would have lacked, according to the panel, was such a reasonable expectation that administering more than 300 mg/day in the presence of a strong CYP3A inhibitor would be safe. Indeed, the Board went so far as to say the skilled worker would have had "no expectation" of such success in view of the cited art (keeping in mind the statements in Lee regarding the safety of the combination of mifepristone and a strong CYP3A inhibitor being unknown). The Federal Circuit found these circumstances to be dispositive on this issue, citing Honeywell Int'l Inc. v. Mexichem Amanco Holding S.A. DE C.V., 865 F.3d 1348, 1356 (Fed. Cir. 2017), for the principle that where there is no expectation of success there can be no reasonable expectation of success. The opinion specifically addressed Teva's expert's testimony, regarding what the Court considered contradictory statements prior to IPR institution ("it was reasonably likely that 600 mg [per day of mifepristone] would be well tolerated and therapeutically effective") and afterwards (wherein the expert stated "unequivocally" that "a skilled artisan 'would have no expectation as to whether the co-administration of 600 mg of mifepristone with ketoconazole would be safe'").
Next considering Teva's range argument, the panel set forth its basis for rejecting the argument, that "Teva had failed to prove the general working conditions disclosed in the prior art encompass the claimed invention." This is based on the Court's precedent that "where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation," citing E.I. DuPont de Nemours & Co. v. Synvina C.V., 904 F.3d 996, 1006 (Fed. Cir. 2018). The "general working conditions" under consideration in the Court's range cases involved instances where "prior art ranges and claimed ranges either overlap or are close enough such that one skilled in the art would have expected them to have the same properties," citing, inter alia, Valeant Pharms. Int'l, Inc. v. Mylan Pharms. Inc., 955 F.3d 25, 32 (Fed. Cir. 2020). Instead of a range the Board found, the prior art here recited a particular dose (300 mg/day), a conclusion the Federal Circuit held was supported by substantial evidence including the Korlym label and certain industry publications not specifically referenced in the opinion that voiced consistent limitations on mifepristone doses in the presence of strong CYP3A inhibitors. Relying on the Board's findings on reasonable expectation of success the panel rejected Teva's argument that prior art monotherapy (i.e., mifepristone doses in the absence of strong CYP3A inhibitors) supported their obviousness argument on the basis that the skilled worker would have had no expectation of success regarding combination therapy based on these monotherapies.
As for those eternal verities, the ones applied by the Federal Circuit here were the requirement for a showing that the skilled worker would have had a reasonable expectation of success in achieving the claimed invention in view of the asserted prior art, and that decisions of the Board on questions of fact supported by substantial evidence are difficult if not almost impossible for the Federal Circuit to overturn (see, for example, Qiagen North America Holdings Inc. v. Handylab, Inc. (Fed. Cir. 2021); Teva Pharmaceuticals Int'l GmbH v. Eli Lilly & Co., Eli Lilly & Co. v. Teva Pharmaceuticals Int'l GmbH, and Teva Pharmaceuticals Int'l GmbH v. Eli Lilly & Co. (Fed. Cir. 2021); Trustees of Columbia University v. Illumina, Inc. (Fed. Cir. 2021); and In re Fulton (Fed. Cir. 2021), but see, Chemours Company FC, LLC v. Daikin Industries, Ltd. (Fed. Cir. 2021)). In this way the Court's decision was unremarkable except as an example of these fundamental principles.
Teva Pharmaceuticals USA, Inc. v. Corcept Therapeutics, Inc. (Fed. Cir. 2021)
Panel: Chief Judge Moore and Circuit Judges Newman and Reyna
Opinion by Chief Judge Moore
