Failure to Show a Reasonable Expectation of Success Dooms Obviousness Allegations

In Teva Pharmaceuticals USA, Inc. v. Corcept Therapeutics, Inc., No. 21-1360, slip op. (Fed. Cir. Dec. 7, 2021) (“Slip Op.”), the Federal Circuit affirmed the PTAB’s decision that Corcept’s patent for methods of treating Cushing’s disease by co-administering two different drugs was not obvious—even where the prior art directed one to combine the two—because there was no reasonable expectation of success shown in the prior art for the specific dose claimed in the patent.

The patent claims, in pertinent part, “A method of treating Cushing’s syndrome … comprising … administering the adjusted once-daily dose of 600 mg mifepristone and a strong CYP3A inhibitor to the patient.” Id. at 3. The claims protect Corcept’s Korlym product, a mifepristone tablet. The Korlym label warns against using mifepristone “with strong CYP3A inhibitors” and limits doses to “300 mg/day when used with strong CYP3A inhibitors.” Id. at 3–4. When approving Korlym the FDA issued the “Lee memo,” requiring Corcept to conduct a drug-drug interaction study with mifepristone and a strong CYP3A inhibitor. Id. at 3. The Korlym label warns against using mifepristone “with strong CYP3A inhibitors” and limits doses to “300 mg/day when used with strong CYP3A inhibitors.” Id. at 3–4. Corcept filed the patent at issue based on the results of the FDA-required study, which supported using the higher dosage amount. Teva argued that the claims were obvious over the Korlym label and the Lee memo, optionally in combination with FDA guidance on drug-drug interaction studies.

The PTAB concluded that Teva failed to prove obviousness because it did not show that a skilled artisan “would have had a reasonable expectation of success in safely co-administering to a patient doses above 300 mg of mifepristone with a strong CYP3A inhibitor.” Final Decision at *17 (emphasis added). Teva appealed.

On appeal, Teva argued that the PTAB committed two errors in concluding that the claims were not obvious: (1) it “required precise predictability, rather than a reasonable expectation of success in achieving the claimed invention”; and (2) it failed to apply the Federal Circuit’s “prior-art-range precedents.” Slip Op. at 5. The Federal Circuit Panel rejected both arguments.

The PTAB “did not err by requiring Teva to show a reasonable expectation of success for a specific mifepristone dosage.”

The panel explained that a reasonable expectation of success analysis “must be tied to the scope of the claimed invention.” Id. (citing Allergan, Inc. v. Apotex Inc., 753 F.3d 952, 966 (Fed. Cir. 2014); Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1366 (Fed. Cir. 2016)). Because the claims cover a specific dosage of mifepristone, the analysis must consider that specific amount. The panel explained that Teva was not “required to prove a skilled artisan would have precisely predicted safe co-administration of 600 mg of mifepristone” because “[a]bsolute predictability is not required.” Id. Teva was, however, required “to prove a reasonable expectation of success in achieving the specific invention claimed, a 600 mg dosage.” Id.

Here, a skilled artisan would not have reasonably “expected co-administration of more than 300 mg of mifepristone with strong CYP3A inhibitor” to be safe or successful. Id. at 6-7 (citing Final Decision at *22). Because there was no expectation of success for any dosage over 300 mg, there could not have been an expectation of success for the claimed 600 mg dosage. The panel explained that “[n]othing about this analysis required precise predictability, only a reasonable expectation of success tied to the claimed invention.” Id.

The PTAB did not err in finding that “the prior art ranges do not overlap with the claimed range”

The panel acknowledged that “prior-art-range precedents” establish that “obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art,” although “overlap is not strictly necessary.” Id. at 8–9 (citing E.I. DuPont de Nemours & Co. v. Synvina C.V., 904 F.3d 996, 1006 (Fed. Cir. 2018)). But under these circumstances, “the general working conditions disclosed in the prior art did not encompass the claimed invention, i.e., there was no overlap in ranges.” Id. at 9. The Korlym label warned against taking mifepristone with a strong CYP3A inhibitor, and limited any co-administration to 300 mg/day. This 300 mg/day cap was also repeated in industry publications. Thus, “the prior art capped the range of co-administration dosages at 300 mg/day.” Id.

Teva argued that the claimed range overlaps with monotherapy dosages in the prior art.  However, because the claimed range was limited to co-administration, the panel explained that the proper question was “whether a skilled artisan would have expected monotherapy and co-administration dosages to behave similarly.” Id. at 9–10. Here, a “skilled artisan would have no such expectation.” Id. at 10. 

Conclusion

Although Teva argued that this was an “uncommonly clear-cut obviousness case” where the prior art discloses “the problem, … the solution, … and the way to find the solution,” the panel disagreed. As the panel explained: “At best, the prior art directed a skilled artisan to try combing the Korlym Label, Lee, and the FDA guidance. But without showing a reasonable expectation of success, Teva did not prove obviousness.” Id. Thus, this decision reinforces the importance of establishing whether the prior art demonstrates a reasonable expectation of success when considering obviousness allegations against patent claims.