DCT

2:21-cv-05034

Corcept Therap Inc v. Hikma Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:21-cv-05034, D.N.J., 03/12/21
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant maintains its U.S. headquarters in Berkeley Heights, NJ, conducts continuous business in the district, and the district will be a destination for the accused product.
  • Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff’s KORLYM® (mifepristone) drug product constitutes an act of infringement of four patents related to methods of administering mifepristone to treat Cushing's syndrome.
  • Technical Context: The patents relate to pharmaceutical dosing methods for mifepristone, a treatment for the rare endocrine disorder Cushing's syndrome, focusing on managing drug-drug interactions and optimizing drug absorption based on food intake.
  • Key Procedural History: This action was triggered by Defendant’s Paragraph IV Certification alleging that Plaintiff's patents are invalid, unenforceable, or will not be infringed by its proposed generic product. Plaintiff has previously litigated related patents against other generic manufacturers. U.S. Patent No. 10,195,214 was the subject of a Post-Grant Review (PGR) proceeding initiated by a third party, which concluded with a finding that the challenged claims were patentable.

Case Timeline

Date Event
2011-11-18 Priority Date for ’216 and ’801 Patents
2017-03-01 Priority Date for ’214 and ’800 Patents
2019-02-05 U.S. Patent No. 10,195,214 Issues
2019-12-10 U.S. Patent No. 10,500,216 Issues
2020-11-24 U.S. Patent No. 10,842,800 Issues
2020-11-24 U.S. Patent No. 10,842,801 Issues
2021-01-29 Defendant sends Paragraph IV Notice Letter to Plaintiff
2021-03-12 Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

No probative visual evidence provided in complaint.

U.S. Patent No. 10,195,214 - "Concomitant Administration of Glucocorticoid Receptor Modulators and CYP3A Inhibitors"

This patent, "the ’214 Patent," issued February 5, 2019 (Compl. ¶4).

The Invention Explained

  • Problem Addressed: The patent's background section describes the risk of adverse drug-drug interactions when two drugs are metabolized by the same liver enzyme system (Compl. Ex. A, ’214 Patent, col. 3:1-15). Specifically, administering a strong CYP3A enzyme inhibitor (such as the antifungal ketoconazole) with a drug that is metabolized by CYP3A (such as mifepristone) is expected to dangerously increase the concentration of the latter drug, potentially leading to toxicity (Compl. Ex. A, ’214 Patent, col. 3:16-24).
  • The Patented Solution: The invention is based on the discovery that mifepristone can be safely and effectively co-administered with a strong CYP3A inhibitor by reducing the dose of mifepristone (Compl. Ex. A, ’214 Patent, Abstract). This dose adjustment compensates for the metabolic inhibition, allowing patients to receive the therapeutic benefits of both drugs while mitigating the risk of toxicity from elevated mifepristone levels (Compl. Ex. A, ’214 Patent, col. 4:1-12).
  • Technical Importance: This method enables a combination therapy regimen for complex conditions like Cushing's syndrome that might otherwise be considered unsafe, thereby expanding treatment options for patients requiring multiple medications (Compl. Ex. A, ’214 Patent, col. 11:32-35).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims without specification; independent claim 1 is representative (Compl. ¶25).
  • Essential elements of Claim 1:
    • A method of treating Cushing's syndrome in a patient taking an original once-daily dose of 1200 mg or 900 mg of mifepristone.
    • The method comprises reducing the dose to an adjusted once-daily dose of 600 mg of mifepristone.
    • The method further comprises administering this adjusted dose of mifepristone along with a strong CYP3A inhibitor selected from a specified group of drugs (which includes ketoconazole).
  • The complaint does not explicitly reserve the right to assert dependent claims, though this is standard practice.

U.S. Patent No. 10,500,216 - "Optimizing Mifepristone Absorption"

This patent, "the ’216 Patent," issued December 10, 2019 (Compl. ¶5).

The Invention Explained

  • Problem Addressed: The patent's background describes the "food effect," a phenomenon where a drug's absorption into the bloodstream is unpredictable and can vary significantly depending on whether it is taken with food or in a fasted state (Compl. Ex. B, ’216 Patent, col. 1:12-18). For mifepristone, this variability can result in some patients receiving plasma concentrations that are too low to be effective (Compl. Ex. B, ’216 Patent, col. 1:37-42).
  • The Patented Solution: The invention provides a method to increase and regularize the absorption of mifepristone by administering it to a patient within a specific time window (e.g., 30 minutes or 1 hour) after the patient has consumed a meal (Compl. Ex. B, ’216 Patent, Abstract). This method increases both the peak plasma concentration (Cmax) and the total drug exposure (Area Under the Curve, or AUC), thereby enhancing the drug's therapeutic benefit (Compl. Ex. B, ’216 Patent, col. 2:5-12).
  • Technical Importance: This dosing instruction provides a simple way to overcome patient-to-patient variability in drug absorption, making the treatment's effect more predictable and potentially more effective at a given dose (Compl. Ex. B, ’216 Patent, col. 2:19-25).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims without specification; independent claim 1 is representative (Compl. ¶33).
  • Essential elements of Claim 1:
    • A method of improving mifepristone absorption in a patient with Cushing's Syndrome.
    • The method comprises administering an oral dose of 1200 mg per day of mifepristone for at least 7 days.
    • The dose is administered within 30 minutes after consuming a meal.
    • This administration results in an increase in AUC of at least 44% compared to administration in a fasted state.
  • The complaint does not explicitly reserve the right to assert dependent claims, though this is standard practice.

U.S. Patent No. 10,842,800 - "Concomitant Administration of Glucocorticoid Receptor Modulators and CYP3A Inhibitors"

This patent, "the ’800 Patent," issued November 24, 2020 (Compl. ¶6).

  • Technology Synopsis: Similar to the ’214 Patent, this patent addresses the drug-drug interaction between mifepristone and strong CYP3A inhibitors. The invention provides a method for controlling hyperglycemia in Cushing's syndrome patients by reducing a patient's mifepristone dose from 1200 mg/day to an adjusted dose of 900 mg/day when co-administered with a strong CYP3A inhibitor (Compl. Ex. C, ’800 Patent, Abstract; col. 67:31-48).
  • Asserted Claims: The complaint asserts "one or more claims"; independent claim 1 is representative (Compl. ¶41).
  • Accused Features: Infringement is alleged based on Defendant's ANDA filing and the contention that its proposed product label will encourage medical professionals and patients to practice the claimed dosing method (Compl. ¶¶ 41, 44).

U.S. Patent No. 10,842,801 - "Optimizing Mifepristone Absorption"

This patent, "the ’801 Patent," issued November 24, 2020 (Compl. ¶7).

  • Technology Synopsis: Similar to the ’216 Patent, this patent addresses the "food effect" on mifepristone absorption. The invention claims a method for improving absorption in Cushing's syndrome patients by administering a 900 mg daily dose of mifepristone within about 30 minutes after a meal, resulting in an AUC increase of at least 44% compared to administration in a fasted state (Compl. Ex. D, ’801 Patent, Abstract; col. 13:1-13).
  • Asserted Claims: The complaint asserts "one or more claims"; independent claim 1 is representative (Compl. ¶49).
  • Accused Features: Infringement is alleged based on Defendant's ANDA filing and the allegation that the proposed product labeling will instruct or encourage users to take the generic drug with food in a manner that infringes the claimed method (Compl. ¶¶ 49, 52).

III. The Accused Instrumentality

  • Product Identification: Defendant Hikma’s proposed generic 300 mg mifepristone drug product, for which it seeks FDA approval via ANDA No. 215242 ("Hikma's Proposed Product") (Compl. ¶1).
  • Functionality and Market Context: The proposed product is a generic version of Plaintiff Corcept's KORLYM®, which is an FDA-approved medication for treating hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing’s syndrome (Compl. ¶8). The act of infringement alleged in this Hatch-Waxman action is the filing of the ANDA itself, which seeks approval to market a generic version prior to the expiration of the patents-in-suit (Compl. ¶19). The complaint alleges that the proposed labeling for Hikma's product will instruct or encourage physicians and patients to use the product in a manner that directly infringes the patented methods of use (Compl. ¶¶ 28, 36, 44, 52).

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or sufficient detail to construct one. The infringement theory is based on the act of filing ANDA No. 215242 for a generic version of KORLYM® and the allegation that the proposed product label will instruct users in a manner that practices the claimed methods (Compl. ¶¶ 19, 25, 33, 41, 49).

  • Identified Points of Contention:
    • Scope Questions (’214 and ’800 Patents): A central question will be whether the language in Hikma’s proposed label constitutes an affirmative instruction or encouragement to perform the specific dose reductions recited in the claims (e.g., from 1200 mg to 900 mg, or from 1200/900 mg to 600 mg) when co-administered with a strong CYP3A inhibitor. The dispute may turn on whether a general warning about drug interactions and potential dose adjustments on the label can be proven to induce infringement of these highly specific, quantitative method steps.
    • Technical Questions (’216 and ’801 Patents): The analysis will raise the question of whether Hikma's label instructs patients to take mifepristone with a meal for the specific patented purpose of achieving increased bioavailability, and whether that instruction will necessarily result in the claimed quantitative outcome (an AUC increase of "at least 44%"). A potential defense could be that any instruction to take the drug with food is for tolerability rather than absorption, and that the 44% threshold is not a guaranteed outcome of following the label's instructions.

V. Key Claim Terms for Construction

The Term: "reducing the original once-daily dose... to an adjusted once-daily dose" (’214 Patent, Claim 1; ’800 Patent, Claim 1)

  • Context and Importance: This active method step is the core of the inventions claimed in the ’214 and ’800 patents. The infringement analysis for inducement will depend heavily on whether the instructions on Hikma's proposed label can be interpreted as directing a prescriber to perform this specific act of reduction between the claimed dosages.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification describes dose reduction as a general principle to ensure safety and provides various percentage-based examples, which may support an argument that any label instruction leading to a clinically meaningful dose reduction in this context falls within the claim's scope (Compl. Ex. A, ’214 Patent, col. 5:14-22).
    • Evidence for a Narrower Interpretation: The claims recite highly specific numerical starting points and endpoints for the dose reduction (e.g., "1200 mg... to an adjusted... dose of 900 milligrams"). This specificity may support a narrower construction where infringement requires inducing a reduction between these exact values, a scenario a generic label might not explicitly describe (Compl. Ex. C, ’800 Patent, col. 67:31-48).

The Term: "increase in AUC being at least 44%" (’216 Patent, Claim 1; ’801 Patent, Claim 1)

  • Context and Importance: This limitation defines the patented method not just by the act of taking the drug with a meal, but by the quantitative result of that act. Practitioners may focus on this term because it links the infringement analysis to a specific pharmacokinetic outcome, which may not be explicitly mentioned on a product label.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patents' detailed description and clinical data tables show that administering mifepristone with a meal consistently leads to significant AUC increases, with examples exceeding the 44% threshold (Compl. Ex. B, ’216 Patent, Table 1, showing a 65% increase). This may support an argument that an instruction to take the drug with food is an instruction to achieve this known and intended result.
    • Evidence for a Narrower Interpretation: The term recites a specific numerical floor ("at least 44%"). This language may support an argument that infringement only occurs if following the label's instructions necessarily and consistently produces this quantitative result in a typical patient, raising a question of whether this functional outcome is an enforceable limitation on a method of administration claim.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement for all four patents-in-suit. The basis for these allegations is that upon approval of its ANDA, Hikma will intentionally encourage direct infringement by physicians and patients through the instructions provided on its proposed product label and in related marketing materials (Compl. ¶¶ 28, 36, 44, 52). Contributory infringement is also alleged on the basis that the proposed product is designed for an infringing use and lacks a substantial non-infringing use (Compl. ¶¶ 29, 37, 45, 53).
  • Willful Infringement: The complaint does not contain a separate count for willful infringement. However, the allegations state that Defendant has knowledge of the patents-in-suit, at least as of the date it sent its Paragraph IV Notice Letter, which could support a future claim for post-suit willfulness (Compl. ¶20).

VII. Analyst’s Conclusion: Key Questions for the Case

  • A core issue will be one of induced infringement: can the general instructions and warnings anticipated on a generic drug label be proven to constitute specific intent to encourage infringement of Corcept's highly quantitative and specific method claims? The case will likely depend on whether Hikma's proposed label directs physicians and patients to perform the exact dose reductions or achieve the specific pharmacokinetic outcomes recited in the patents.
  • A second key question will be one of claim scope and enforceability: can Corcept prove that following the instructions on Hikma’s label will necessarily result in the claimed functional outcome (e.g., an AUC increase of "at least 44%")? This raises the evidentiary challenge of linking the language of a product insert to a specific, quantitative clinical result for purposes of infringement.