DCT

1:22-cv-01226

Otsuka Pharmaceutical Co Ltd v. Mylan Laboratories Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:22-cv-01226, D. Del., 09/20/2022
  • Venue Allegations: Venue is alleged to be proper based on Defendant Viatris Inc.’s incorporation in Delaware, Defendant Mylan Laboratories Limited’s status as a foreign corporation, and an alter-ego theory asserting that Defendant Mylan Pharmaceuticals Inc.’s corporate identity is subsumed by Viatris, thereby imputing Viatris’s Delaware residency to it.
  • Core Dispute: Plaintiffs allege that Defendants’ filing of an Abbreviated New Drug Application (ANDA) for a generic version of the antipsychotic drug ABILIFY MAINTENA® constitutes an act of infringement of a patent covering methods for administering the drug to patients with specific metabolic impairments.
  • Technical Context: The technology relates to personalized medicine, specifically the adjustment of dosing regimens for a long-acting injectable antipsychotic based on a patient's genetic profile affecting drug metabolism.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendants' filing of ANDA No. 216608 seeking FDA approval for a generic drug prior to the expiration of the patent-in-suit. The complaint notes that the same ANDA was the subject of prior lawsuits involving different patents. Plaintiff Otsuka has granted co-plaintiff Lundbeck an exclusive license to the patent-in-suit.

Case Timeline

Date Event
2013-02-28 FDA approves New Drug Application for ABILIFY MAINTENA®
2013-09-24 Earliest Priority Date for ’087 Patent
2022-02-23 Defendants file ANDA No. 216608 (on or before this date)
2022-08-02 ’087 Patent is issued
2022-09-20 Complaint is filed

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

U.S. Patent No. 11,400,087 - "Method of Providing Aripiprazole to Patients Having Impaired CYP2D6 or CYP3A4 Enzyme Function"

  • Patent Identification: U.S. Patent No. 11,400,087, "Method of Providing Aripiprazole to Patients Having Impaired CYP2D6 or CYP3A4 Enzyme Function," issued August 2, 2022.

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of administering the antipsychotic drug aripiprazole, particularly in a long-acting injectable form, to patients with varying metabolic rates ('087 Patent, col. 3:11-29). Aripiprazole is primarily metabolized by the CYP2D6 and CYP3A4 enzymes, but some patients are "poor metabolizers" with little to no enzyme function, while others may take co-medications that inhibit these enzymes ('087 Patent, col. 3:32-49; col. 4:1-4). For these patients, a standard dose of a long-acting formulation, which cannot be easily adjusted after injection, can lead to drug accumulation and potentially serious side effects ('087 Patent, col. 4:56-67).
  • The Patented Solution: The invention provides a method for initiating aripiprazole treatment in patients with impaired enzyme function by administering a reduced, or "adjusted," starting dose of a long-acting formulation ('087 Patent, Abstract). The specification describes calculating this adjusted dose as a percentage of the dose recommended for a patient with normal metabolism (e.g., 75% for a poor metabolizer) to achieve a safe and therapeutic plasma level over approximately one month ('087 Patent, col. 5:9-30). This method tailors the initial therapy to the patient's specific metabolic profile.
  • Technical Importance: The claimed method provides a systematic approach to personalized medicine for long-acting injectable antipsychotics, aiming to improve the safety and efficacy of treatment for genetically distinct patient subpopulations ('087 Patent, col. 3:20-33).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" without specifying them (Compl. ¶79). Independent claims 1 and 16 are representative of the patented methods.
  • Claim 1 (Independent): A method of treating schizophrenia or bipolar I disorder in a patient comprising:
    • intramuscularly administering to the patient a long-acting suspension of an adjusted dose of aripiprazole of about 300 mg;
    • co-administering to the patient an oral antipsychotic after the first administration;
    • wherein the dose is systemically released over about one month; and
    • the patient is a CYP2D6 poor metabolizer.
  • The complaint does not foreclose the possibility of asserting other independent or dependent claims.

III. The Accused Instrumentality

Product Identification

  • Defendants' proposed generic aripiprazole for extended-release injectable suspension in 300 mg/vial and 400 mg/vial strengths, which are the subject of ANDA No. 216608 (Compl. ¶1, ¶69).

Functionality and Market Context

  • The complaint alleges that Defendants' products are generic versions of Plaintiffs' ABILIFY MAINTENA® and are "pharmaceutically and therapeutically equivalent" (Compl. ¶2, ¶77). The act of infringement alleged under the Hatch-Waxman Act is the submission of the ANDA itself, which seeks FDA approval to market this generic product for the same indications as the branded drug before the expiration of the ’087 Patent (Compl. ¶1, ¶79). The complaint states the Defendants intend to market and sell the products throughout the United States upon approval (Compl. ¶74).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not include a claim chart. The infringement theory is based on inducement, alleging that the proposed package insert for Defendants' generic product will instruct healthcare professionals to perform the patented method (Compl. ¶83). The following chart summarizes this theory for representative Claim 1.

’087 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating schizophrenia or bipolar I disorder in a patient comprising: The proposed package insert for Defendants’ generic product, which is equivalent to ABILIFY MAINTENA®, will instruct its use for treating schizophrenia and bipolar I disorder. ¶64, ¶77 col. 9:43-44
intramuscularly administering to the patient a long-acting suspension of an adjusted dose of aripiprazole of about 300 mg The proposed package insert will instruct the intramuscular administration of a 300 mg dose, which constitutes an "adjusted dose" when prescribed for the specified patient type. ¶1, ¶69, ¶83 col. 9:56-58
and co-administering to the patient an oral antipsychotic after a first administration of said adjusted dose of the long-acting suspension The proposed package insert will instruct or recommend the co-administration of an oral antipsychotic during the initiation phase of treatment. ¶83 col. 9:59-62
wherein...the patient is a CYP2D6 poor metabolizer. The proposed package insert will instruct physicians to administer this specific dosage regimen to patients identified as CYP2D6 poor metabolizers. ¶83 col. 10:1-2
  • Identified Points of Contention:
    • Scope Questions: A primary issue will be whether the specific language of Defendants' proposed product label recommends or encourages performing every step of the claimed method. The dispute may center on whether the label explicitly instructs the administration of the "about 300 mg" dose as an adjusted dose specifically for a "CYP2D6 poor metabolizer," or if the dosage instructions are more general, leaving the connection to be inferred by the physician.
    • Evidentiary Questions: The case for induced infringement rests entirely on the content of the proposed label submitted with ANDA No. 216608. A central question will be what that label actually says and whether its instructions rise to the level of encouraging, recommending, or promoting the performance of the patented method as a whole.

V. Key Claim Terms for Construction

  • The Term: "adjusted dose"

    • Context and Importance: This term is the core of the invention, which is a method of adjusting a dose for specific patient types. Its construction will define what constitutes an infringing act of administration. Practitioners may focus on this term because its scope will determine whether the dosage information on the accused label falls within the claim.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The term's plain meaning could be argued to cover any dose that deviates from a standard or default dose for any reason.
      • Evidence for a Narrower Interpretation: The specification consistently defines the "adjusted dose" with reference to a "patient with normal CYP2D6 and CYP3A4 enzyme function" and provides specific, calculated reductions, such as "about 75% of the recommended initial dose" ('087 Patent, col. 5:25-27). This suggests "adjusted dose" is not just any different dose, but one that is specifically reduced according to the metabolic impairment described in the patent.

  • The Term: "CYP2D6 poor metabolizer"

    • Context and Importance: This term defines the patient population for Claim 1. The infringement analysis depends on whether the accused label instructs treatment for patients meeting this definition. The required level of clinical or genetic certainty to classify a patient as a "poor metabolizer" will be a key issue.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A party might argue the term covers any patient with a clinically significant reduction in CYP2D6 enzyme activity.
      • Evidence for a Narrower Interpretation: The specification states that such patients "have little or no CYP2D6...enzyme function" and that these traits are due to "phenotypic variability" ('087 Patent, col. 3:32-41). This language could support a narrower definition requiring a near-total lack of enzyme function, potentially confirmed by genetic testing.

VI. Other Allegations

  • Indirect Infringement: The complaint's central theory is induced infringement under 35 U.S.C. § 271(b). It alleges that Defendants know of the ’087 Patent and that their proposed package insert will "recommend, suggest, encourage and/or instruct" healthcare professionals and patients to use the generic product in a way that directly infringes the patent's method claims (Compl. ¶82-83, ¶98-99).
  • Willful Infringement: The complaint does not contain a formal count for willful infringement. However, it alleges that Defendants have "actual knowledge of the '087 patent" through its public listing in the FDA's Orange Book (Compl. ¶78, ¶94). It also requests a declaration that this is an "exceptional case" and seeks attorney fees, which is the remedy for willfulness or other litigation misconduct (Compl., Request for Relief, G). These allegations preserve the option to argue for enhanced damages later in the litigation.

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

  • A central issue will be one of induced infringement: does the precise text of the Defendants’ proposed generic drug label, as submitted to the FDA, contain instructions that actively encourage or recommend that physicians perform each and every step of the asserted method claims? The case will likely depend on whether the label creates a direct link between the patient type (e.g., "CYP2D6 poor metabolizer") and the specific "adjusted dose" claimed in the patent.
  • The outcome may also hinge on claim construction: can the term "adjusted dose", as used in the claims, be limited to the specific, calculated percentage reductions from a "normal" dose described in the patent's specification? A narrow construction would require Plaintiffs to show that the accused label instructs this specific calculation, while a broader construction might capture more generalized dosage guidance.