REASONABLE-EXPECTATION-OF-SUCCESS REQUIREMENT CANNOT BE SATISFIED WHEN THERE IS NO EXPECTATION OF SUCCESS
| February 4, 2022
Teva Pharmaceuticals USA v. Corcept Therapeutics, Inc.
Decided December 7, 2021
Moore, Newman and Reyna (Opinion by Moore)
This precedential opinion illustrates the importance of preparing your expert for deposition. Although an expert declaration was effective in having a Post Grant Review instituted on claims 1-13 of U.S. Patent No. 10,195,214, the expert’s post-institution deposition testimony was instrumental in upholding the validity of the claims. This opinion not only addresses obviousness with respect to the reasonable expectation of success requirement, but also obviousness of ranges, a topic covered by Michael Caridi earlier this month in Indivior UK Ltd., v. Dr. Reddy’s Labs S.A., Dr. Reddy’s Labs, Inc.
Mifepristone was developed as an anti-progestin in the 1980s and was later discovered to likely inhibit the effect of cortisol on tissues, suggesting that it could be used to treat Cushing’s syndrome (a disease caused by excessive levels of cortisol). Corcept filed for a New Drug Application (NDA) for Korlym (a 300 mg mifepristone tablet) to control hyperglycemia secondary to hypercortisolism in certain patients with Cushing’s syndrome. The NDA application was approved with a few post marketing requirements, one including 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 CYP3A inhibitor). A memorandum provided by the FDA explained that “[t]he degree of change in exposure of mifepristone when co-administered with strong CYP3A inhibitors is unknown. . .”.
In approving Corcept’s NDA, the FDA also approved the Korlym label recommending a dose of 300 mg once daily and allowing for increasing dosage in 300 mg increments to a maximum 1200 mg once daily. In addition, the label warned against using mifepristone with strong CYP3A inhibitors and limited the dose to 300 mg per day when used with strong CYP3A inhibitors.
Corcept conducted the drug-drug interaction study and collected data on co-administration of mifepristone with a strong CYP3A inhibitor and received the ‘214 patent.
Teva sought post-grant review after Corcept asserted the ‘214 patent in district court, arguing that the claims would have been obvious based on the Korlym label and the FDA memorandum, optionally in combination with FDA guidance on drug-drug interaction. Furthermore, Teva provided an expert declaration of Dr. Greenblatt opining that it was reasonably likely that 600 mg mifepristone would be well tolerated and therapeutically effective when co-administered with a strong CYP3A inhibitor.
The Patent Trial and Appeal Board (PTAB) found that Teva had failed to prove that claims 1-13 would have been obvious. The PTAB construed the claims to require safe administration of mifepristone, and that Teva failed to show that one of ordinary skill in the art would have had a reasonable expectation of success for safe co-administration of more than 300 mg mifepristone with a strong CYP3A inhibitor.
Teva asserted that the PTAB had committed two errors: (1) that the PTAB erred in requiring precise predictability rather than a reasonable expectation of success, and (2) that the PTAB erred when it found Teva had failed to prove the general working conditions (ranges) disclosed in the prior art encompassed the claimed invention. The CAFC did not agree.
1. Reasonable Expectation of Success
The reasonable expectation of success analysis must be tied to the scope of the claims.
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 strongCYP3A 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 claims require safe co-administration of a specific amount of mifepristone with a strong CYP3A inhibitor. Teva failed to establish that one would have reasonably expected co-administration of more than 300 mg mifepristone with a strong CPY3A inhibitor to be safe for treatment of Cushing’s syndrome. The PTAB went further to find that one of ordinary skill in the art would have had no expectation of success. Although not in the CAFC’s opinion, the deposition testimony of Teva’s expert (Dr. Greenblatt) was devastating.From the deposition:
[Patent Owner’s Counsel]: Well, okay. With all those assumptions built into this, was this — was the result set forth here that there was little to no increase in adverse events, was that result predictable?
[Dr. Greenblatt]: It’s — the result is neither predictable or unpredictable. It is what it is. It’s the study was done as mandated by the FDA to get at the truth, and here’s the outcome of the study.
[Patent Owner’s Counsel]: So a person of skill in the art would not have expected there to be no increase in adverse events?
[Dr. Greenblatt]: The study was done to, in part, to answer that question, not to address an expectation. I don’t believe that there would be any expectation. You don’t know what’s going to happen, which is why you do the study.
[Patent Owner’s Counsel]: So if the same testing had shown that a dose of 600 mg mifepristone could not be safely administered with ketoconazole, would that have been expected by a person of skill in the art?
. . .
[Dr. Greenblatt]: Yeah, the same answer. I don’t think there’s an expectation. You’re doing the study to find out what the result is to get the scientific truth.
The PTAB had discredited Dr. Greenblatt’s pre-institution testimony based on this post-institution testimony which unequivocally stated that one of ordinary skill would have no expectation as to whether 600 mg of mifepristone and ketoconazole would be safe. 2. Prior Art Range Precedence
Teva had asserted that the sole administration of mifepristone up to 1200 mg was an overlap in the range required by claim 1. This argument failed because the evidence of recorded only supported that the general working conditions for co-administration was shown to be 300 mg/day. As such, there was no overlap. Thus. The PTAB’s finding that the prior art ranges do not overlap was supported by substantial evidence.
Takeaways
- Make sure your expert is prepared.
- Obviousness based on the reasonable-expectation-of-success analysis must be tied to the scope of the claims.
- General working conditions in the prior art need to be analyzed with respect to the scope of the claims.
