Teva Pharmaceuticals USA Inc v. Corcept Therapeutics Inc

1. Case Identification

• Case #: PGR2019-00048
• Patent #: 10,195,214
• Filed: May 7, 2019
• Petitioner(s): Teva Pharmaceuticals USA, Inc.
• Patent Owner(s): Corcept Therapeutics, Inc.
• Challenged Claims: 1-13

2. Patent Overview

• Title: Concomitant Administration of Glucocorticoid Receptor Modulators and CYP3A Inhibitors
• Brief Description: The ’214 patent describes a method for treating Cushing's syndrome in patients already taking a high dose (900 or 1200 mg/day) of the glucocorticoid receptor modulator mifepristone. The method involves reducing the mifepristone dose to 600 mg/day and co-administering it with a strong CYP3A inhibitor, such as ketoconazole.

3. Grounds for Unpatentability

Ground 1: Obviousness over Korlym Label and Lee - Claims 1-13 are obvious over the Korlym Label in view of Lee.

• Prior Art Relied Upon: Korlym Label (2012 FDA-approved package insert for mifepristone) and Lee (Office of Clinical Pharmacology Review NDA 20687, 2012).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the combination of the Korlym Label and Lee disclosed all elements of the challenged claims except the specific 600 mg adjusted dose of mifepristone. The Korlym Label taught treating Cushing's syndrome with mifepristone (brand name Korlym) at doses of 300-1200 mg/day. It also explicitly noted that co-administration with strong CYP3A inhibitors (like ketoconazole) could increase mifepristone plasma concentrations, might require a dose reduction, and recommended a conservative limit of 300 mg/day when used with such inhibitors. The Lee reference, part of the FDA's approval package for Korlym, disclosed that this 300 mg limit was a precautionary measure, not based on safety data, and that the FDA had imposed a post-marketing requirement on the Patent Owner to conduct a drug-drug interaction (DDI) study to determine the appropriate dose.
  • Motivation to Combine: A person of ordinary skill in the art (POSA) would combine these references because they are inextricably linked as part of the Korlym FDA approval package. Lee explained the context and rationale for the dosing recommendations in the Korlym Label. A POSA seeking to safely co-administer these known drugs would be motivated to understand this context, which explicitly encouraged further study to determine an optimal dose above the conservative 300 mg limit.
  • Expectation of Success: A POSA would have had a reasonable expectation of success in arriving at the claimed method. The Korlym Label permitted mifepristone doses up to 1200 mg, establishing a known safety and efficacy profile at higher doses. Lee revealed that the 300 mg limit for co-administration was not a safety-based ceiling but a temporary placeholder pending a routine DDI study. Therefore, a POSA would reasonably expect that a dose higher than 300 mg, such as 600 mg, would be safe and effective, and that a standard DDI study would successfully identify this optimal range.

Ground 2: Obviousness over Korlym Label, Lee, and FDA Guidance - Claims 1-13 are obvious over the Korlym Label and Lee in view of the FDA Guidance.

• Prior Art Relied Upon: Korlym Label (2012 package insert), Lee (Office of Clinical Pharmacology Review NDA 20687, 2012), and FDA Guidance (2006 guidance document on drug interaction studies).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground built upon the disclosures of the Korlym Label and Lee by adding the FDA Guidance. Petitioner asserted this guidance provided the explicit "how-to" for the routine dose optimization required to arrive at the claimed invention. The FDA Guidance recommended that DDI studies be conducted for drugs metabolized by CYP3A (like mifepristone) to determine if dosage adjustments are needed. It specifically recommended using ketoconazole as the "index inhibitor" for such studies because it produces the largest possible interaction, thereby establishing a worst-case scenario.
  • Motivation to Combine: A POSA, knowing from the Korlym Label and Lee that a DDI study was required to optimize the mifepristone dose, would have been motivated to consult the FDA Guidance, which was the standard industry and regulatory blueprint for designing such studies. The guidance provided the direct motivation and methodology to perform the exact type of DDI study that the FDA required for Korlym.
  • Expectation of Success: The FDA Guidance provided a POSA with a clear, established, and predictable pathway for conducting the DDI study. By following this standard regulatory roadmap, a POSA would have a very high expectation of successfully quantifying the drug interaction and determining the precise, optimized dose (600 mg) for co-administration, confirming that arriving at the claimed invention was a matter of routine optimization, not invention.

4. Key Technical Contentions (Beyond Claim Construction)

• Rebuttal of "Teaching Away": Petitioner contended that the prior art did not teach away from the invention, contrary to the Patent Owner's arguments during prosecution. The 300 mg/day dose limitation in the Korlym Label was not a prohibition or a safety warning against higher doses. The Lee reference clarified it was a conservative, temporary starting point pending a DDI study that the FDA itself mandated. Therefore, the prior art, when read as a whole, affirmatively encouraged investigation to find the optimal dose, rather than discouraging it.
• Rebuttal of "Unexpected Results": Petitioner argued that the observed 28-38% increase in mifepristone exposure from co-administration was not an unexpected result. The petition asserted that for CYP3A-mediated interactions, the precise magnitude cannot be predicted a priori and must be determined empirically via a DDI study. The fact that the result was not a multi-fold increase (a "dramatic spike") was not surprising, but simply one possible outcome within a range of scientifically plausible results. Petitioner argued that equating this inherent unpredictability with patentable "unexpectedness" is legally incorrect, as the process to find the result was a well-known, routine optimization procedure.

5. Arguments Regarding Discretionary Denial

• Arguments against §325(d) Denial: Petitioner argued that this petition did not present the same or substantially the same prior art or arguments previously presented to the Office. Although the examiner considered the Korlym Label, he did so in combination with a different reference (Ulmann) and did not have the benefit of the Lee reference or the FDA Guidance. Petitioner asserted Lee was critical because it directly refuted the "teaching away" and "unexpected results" arguments on which the examiner appeared to have relied to allow the claims.
• Arguments against §314(a) Denial: Petitioner argued that discretionary denial would be inappropriate. This was the first petition filed against the ’214 patent, so serial petition factors did not apply. Furthermore, because trial had not yet been set in the co-pending district court litigation, instituting a Post-Grant Review (PGR) would be an efficient use of resources and consistent with the goal of the AIA to provide an effective alternative to district court litigation.

6. Relief Requested

• Petitioner requested institution of a Post-Grant Review and cancellation of claims 1-13 of Patent 10,195,214 as unpatentable under 35 U.S.C. §103.