DCT

1:22-cv-00114

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-00114, N.D.W. Va., 11/10/2022
  • Venue Allegations: Venue is alleged to be proper because Defendant Mylan Pharmaceuticals Inc. is incorporated in West Virginia, Defendant Viatris Inc. has an established place of business and allegedly committed acts of infringement in the district, and Defendant Mylan Laboratories Limited is a foreign corporation. The complaint also contains extensive alter ego allegations asserting the defendants operate as a single integrated enterprise.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the antipsychotic drug ABILIFY MAINTENA® constitutes an act of infringement of a patent covering methods for administering the drug to specific patient subpopulations.
  • Technical Context: The technology involves a long-acting injectable formulation of aripiprazole, an atypical antipsychotic, and methods for tailoring its dosage to patients with specific genetic metabolic profiles to enhance safety and efficacy.
  • Key Procedural History: This action arises under the Hatch-Waxman Act and follows several prior lawsuits filed by Plaintiffs against the same Defendants concerning the same ANDA but asserting different patents. This complaint was filed in response to Defendants' "Third Notice Letter," which provided a Paragraph IV certification against the patent-in-suit, U.S. Patent No. 11,400,087.

Case Timeline

Date Event
2013-09-24 '087 Patent Priority Date
2022-02-23 Defendants' First Notice Letter Regarding Other Patents
2022-04-08 First Suits Filed Against Defendants
2022-07-26 Defendants' Second Notice Letter Regarding Other Patents
2022-08-02 '087 Patent Issue Date
2022-08-26 Second Delaware Suit Filed Against Defendants
2022-09-09 Second West Virginia Suit Filed Against Defendants
2022-09-20 Third Delaware Suit Filed Against Defendants
2022-09-29 Defendants' Third Notice Letter Regarding '087 Patent
2022-10-17 Fourth Delaware Suit Filed Against Defendants
2022-11-10 Complaint Filing Date

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 describes that the antipsychotic drug aripiprazole is metabolized by two key liver enzymes, CYP2D6 and CYP3A4 ('087 Patent, col. 3:28-33). A patient’s ability to metabolize the drug varies significantly due to genetic factors (e.g., "poor metabolizers") or co-administration of other drugs that inhibit these enzymes ('087 Patent, col. 3:33-48; col. 4:46-52). This variability makes standard dosing of a long-acting injectable formulation risky, as an administered dose cannot be easily adjusted and may lead to sustained periods of over-exposure (and side effects) or under-exposure (and ineffective treatment) ('087 Patent, col. 4:29-45).
  • The Patented Solution: The invention provides a method of treatment that involves adjusting the starting dose of a long-acting injectable aripiprazole formulation for patients identified as having impaired enzyme function. For example, for a patient who is a "CYP2D6 poor metabolizer," the method teaches administering a starting dose that is about 75% of the dose recommended for a patient with normal enzyme function ('087 Patent, col. 5:23-30). This method aims to provide therapeutic drug levels safely and effectively in these specific patient populations.
  • Technical Importance: The claimed method enables a personalized medicine approach for a long-acting injectable drug, tailoring the dosage regimen to a patient's individual metabolic capacity to optimize the balance between therapeutic benefit and potential side effects ('087 Patent, col. 3:10-24).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" of the '087 patent (Compl. ¶80). The first independent claim is Claim 1.
  • The essential elements of independent Claim 1 are:
    • A method of treating schizophrenia or bipolar I disorder in a patient.
    • The method comprises intramuscularly administering a long-acting suspension of an "adjusted dose of aripiprazole of about 300 mg."
    • It further comprises "co-administering... an oral antipsychotic" after the first injection.
    • The injected dose is systemically released over "about one month."
    • The patient is a "CYP2D6 poor metabolizer."

III. The Accused Instrumentality

Product Identification

  • Product Identification: Defendants' generic aripiprazole for extended-release injectable suspension, available in 300 mg/vial and 400 mg/vial dosages, for which Defendants filed Abbreviated New Drug Application (ANDA) No. 216608 (Compl. ¶1, ¶72).

Functionality and Market Context

  • Functionality and Market Context: The accused product is a generic version of Otsuka's branded drug, ABILIFY MAINTENA®, and is intended for the treatment of schizophrenia and maintenance monotherapy of bipolar I disorder (Compl. ¶1, ¶67). The complaint alleges that in the ANDA, Defendants have represented to the FDA that their generic product is pharmaceutically and therapeutically equivalent to ABILIFY MAINTENA® (Compl. ¶78). The complaint also highlights the product's perceived commercial importance, citing a statement from Viatris that its "complex injectables franchise," including the generic version of ABILIFY MAINTENA®, "represents at least a $1 billion peak net sales opportunity" (Compl. ¶62).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint does not contain a detailed claim chart. The following summary is based on the narrative allegations.

'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... comprising: intramuscularly administering to the patient a long-acting suspension of an adjusted dose of aripiprazole of about 300 mg... Defendants are seeking FDA approval for a generic extended-release injectable aripiprazole suspension, including a 300 mg/vial dosage, which is represented as therapeutically equivalent to the branded product. ¶72, ¶78 col. 5:16-22
...and co-administering to the patient an oral antipsychotic after a first administration of said adjusted dose of the long-acting suspension, Defendants' proposed package insert for their generic product will allegedly recommend, suggest, or instruct healthcare professionals on how to use the product, including co-administration with an oral antipsychotic. ¶84 col. 8:12-29
...wherein the dose is systemically released over a period of about one month... Defendants' product is an "extended-release injectable suspension" intended to be administered monthly, as a generic equivalent to ABILIFY MAINTENA®. ¶1, ¶72 col. 5:39-41
...and the patient is a CYP2D6 poor metabolizer. The complaint alleges Defendants know their product will be prescribed to patients, including CYP2D6 poor metabolizers, and that their product label will induce infringement by instructing use that falls within the claim. ¶82, ¶84 col. 5:23-24
  • Identified Points of Contention:
    • Scope Questions: A central question for induced infringement will be whether the language of Defendants' proposed product label constitutes affirmative instruction or encouragement to perform the claimed method. The court will have to determine if the label directs physicians to administer the 300 mg dose specifically to patients identified as CYP2D6 poor metabolizers, or if it merely provides this dose as a general option, leaving the decision to the physician's independent judgment.
    • Technical Questions: The complaint does not provide the proposed product label, so a key factual question is what the label actually says. The infringement analysis will depend entirely on whether the instructions in that label, once produced in discovery, map onto the specific steps and patient population recited in the asserted claims.

V. Key Claim Terms for Construction

  • The Term: "adjusted dose"

  • Context and Importance: This term is at the heart of the invention, as the claims cover a method of using a modified, or "adjusted," dose for a specific patient population. The definition of this term will be critical for determining whether the 300 mg dose described in Defendants' product label constitutes an infringing "adjusted dose" as contemplated by the patent.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification describes the adjustment in relative terms, such as a dose that "provides no more than about 75%" of the amount for a normal patient, which may support an argument that any dose reduced for this sub-population qualifies as "adjusted" ('087 Patent, col. 5:49-54).
    • Evidence for a Narrower Interpretation: Claim 1 recites "an adjusted dose of aripiprazole of about 300 mg." A party could argue the claim itself defines the adjusted dose as being "about 300 mg," tying the term to a specific quantity that is a reduction from an implied standard dose (e.g., 400 mg) ('087 Patent, col. 5:16-22).

  • The Term: "CYP2D6 poor metabolizer"

  • Context and Importance: This term defines the specific patient to whom the claimed method applies. Its construction is crucial for establishing the scope of direct infringement that Defendants are accused of inducing. Practitioners may focus on this term because its definition will determine the size and characteristics of the patient pool covered by the patent.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent describes "poor metabolizers" functionally as patients who "have little or no CYP2D6 or CYP3A4 enzyme function" ('087 Patent, col. 3:38-40). This could support a construction based on general clinical assessment rather than a specific diagnostic test.
    • Evidence for a Narrower Interpretation: The specification discusses the term in the context of "phenotypic variability" and distinguishes these patients from "extensive metabolizers" ('087 Patent, col. 3:31-48). This could support an argument that the term requires an objective classification based on established, quantifiable criteria, such as a specific genetic test result.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b). The factual basis is that Defendants' proposed package insert will allegedly "recommend, suggest, encourage and/or instruct" healthcare professionals to use the generic product in a manner that directly infringes at least one claim of the '087 patent (Compl. ¶84). The complaint also makes a conclusory allegation of contributory infringement (Compl. ¶81).
  • Willful Infringement: The complaint alleges that "Defendants have actual knowledge of the '087 patent, as evidenced by Defendants' Third Notice Letter," which establishes pre-suit knowledge of the patent (Compl. ¶79). While the term "willful" is not used, this allegation provides the foundation for a potential future claim of willful infringement and is reflected in the request for a finding of an exceptional case under 35 U.S.C. § 285 (Compl. p. 25, ¶F).

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

  • A central question of inducement: The case will likely hinge on the specific text of the Defendants' proposed product label. Does the label contain language that rises to the level of actively encouraging or instructing physicians to administer the 300 mg dose of aripiprazole to the specific sub-population of "CYP2D6 poor metabolizers," thereby satisfying the intent standard for induced infringement?
  • A core issue of validity: The patent claims a method of treatment involving a specific dosage regimen for a known patient sub-population. A key question for the court will be whether this claimed method is nonobvious, or if it represents a dosage adjustment that would have been obvious to a person of ordinary skill in the art at the time of the invention, particularly in the context of a known drug and recognized metabolic pathways.
  • An evidentiary question of corporate liability: The complaint extensively details allegations that the multiple corporate defendants are alter egos and operate as a single enterprise. A significant procedural question will be whether the plaintiffs can present sufficient evidence to persuade the court to treat the defendants as a single entity for purposes of liability and venue.