DCT

1:22-cv-01367

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-01367, D. Del., 10/17/2022
  • Venue Allegations: Venue is alleged to be proper in Delaware. The complaint asserts that Defendant Viatris Inc. is incorporated in Delaware, Defendant Mylan Laboratories Limited is a foreign entity that may be sued in any district, and Defendant Mylan Pharmaceuticals Inc., a West Virginia corporation, is subject to venue in Delaware under an alter ego theory of liability that imputes the Delaware residency of its parent, Viatris Inc.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the long-acting injectable antipsychotic ABILIFY MAINTENA® constitutes an act of infringement of a patent directed to methods of dosing specific patient populations.
  • Technical Context: The technology relates to personalized medicine, specifically adjusting the dosage of the antipsychotic drug aripiprazole for patients with genetically impaired liver enzyme function to ensure safety and efficacy.
  • Key Procedural History: This lawsuit is part of a series of litigations between the parties concerning the same ANDA. The complaint states it was filed in response to Defendants' "Third Notice Letter," which provided a Paragraph IV certification against the patent-in-suit. Previous suits were filed in response to earlier notice letters concerning different patents related to the same drug product. Plaintiffs have requested that this action be consolidated with a prior Delaware action.

Case Timeline

Date Event
2013-02-28 FDA approves Otsuka's New Drug Application for ABILIFY MAINTENA®
2013-09-24 Earliest Priority Date for U.S. Patent No. 11,400,087
2022-02-23 Defendants send "First Notice Letter" regarding ANDA No. 216608
2022-07-26 Defendants send "Second Notice Letter"
2022-08-02 U.S. Patent No. 11,400,087 issues
2022-09-29 Defendants send "Third Notice Letter" regarding the ’087 patent
2022-10-17 Complaint 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

Issued August 2, 2022 (’087 Patent)

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of safely administering the antipsychotic drug aripiprazole, which is primarily metabolized by the CYP2D6 and CYP3A4 liver enzymes (’087 Patent, col. 3:25-30). Some patients, known as "poor metabolizers," have genetically impaired enzyme function, causing the drug to accumulate to potentially toxic levels if they receive a standard dose (’087 Patent, col. 3:38-49). This problem is exacerbated with long-acting injectable formulations, as a dose, once administered, cannot be easily adjusted or withdrawn (’087 Patent, col. 2:26-29).
  • The Patented Solution: The patent claims methods for treating schizophrenia or bipolar disorder in these specific patient populations. The core of the solution is administering a pre-emptively "adjusted dose" of a long-acting aripiprazole formulation that is lower than the standard dose recommended for patients with normal enzyme function (’087 Patent, col. 4:51-64). For example, the patent describes administering a dose that is 75% of the normal dose for a CYP2D6 poor metabolizer, thereby accounting for their reduced metabolic capacity from the outset (’087 Patent, col. 5:19-29).
  • Technical Importance: The invention provides a dosing regimen tailored to a patient's specific metabolic phenotype, enabling the use of a long-acting injectable drug in a sub-population that might otherwise be at risk for adverse effects from overexposure (’087 Patent, col. 3:10-24).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the ’087 Patent (Compl. ¶77). Independent claim 1 is representative:
  • Claim 1:
    • 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
    • and co-administering to the patient an oral antipsychotic after a first administration of said adjusted dose of the long-acting suspension,
    • wherein the dose is systemically released over a period of about one month
    • and the patient is a CYP2D6 poor metabolizer.
  • The complaint reserves the right to assert other claims, including dependent claims.

III. The Accused Instrumentality

Product Identification

Defendants' generic aripiprazole for extended-release injectable suspension, available in 300 mg/vial and 400 mg/vial dosages, as described in ANDA No. 216608 (Compl. ¶69).

Functionality and Market Context

The accused product is a generic version of Otsuka’s ABILIFY MAINTENA® and is intended to be pharmaceutically and therapeutically equivalent for the treatment of schizophrenia and bipolar I disorder (Compl. ¶¶64, 75). In this Hatch-Waxman context, the infringement allegation centers not on a currently marketed product, but on the future product that will be marketed if the FDA approves Defendants' ANDA (Compl. ¶1). The functional characteristics relevant to infringement are those that would be described in the proposed product labeling, which allegedly instructs medical professionals on how to administer the drug (Compl. ¶81).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint does not include a claim chart. The infringement theory is based on inducement, where the Defendants' proposed product label for their generic drug is alleged to instruct physicians to perform the patented method.

'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: Defendants’ ANDA seeks approval for a generic version of ABILIFY MAINTENA®, which is a drug used for treating schizophrenia and bipolar I disorder. ¶¶64, 69 col. 9:51-53
intramuscularly administering to the patient a long-acting suspension of an adjusted dose of aripiprazole of about 300 mg Defendants' ANDA is for an extended-release injectable suspension, including a 300 mg/vial dosage. The complaint alleges that the proposed product label will instruct physicians to administer this dose to the specified patient population, thereby constituting the claimed "adjusted dose." ¶¶69, 81 col. 9:54-56
and co-administering to the patient an oral antipsychotic after a first administration... The complaint alleges that the proposed package insert will instruct users on how to engage in an infringing use, which would include co-administration of an oral antipsychotic to achieve and maintain therapeutic levels. ¶81 col. 9:57-59
wherein the dose is systemically released over a period of about one month The accused product is an "extended-release injectable suspension," consistent with a monthly administration schedule. ¶69 col. 9:60-62
and the patient is a CYP2D6 poor metabolizer. The infringement allegation is predicated on the claim that Defendants' proposed label will instruct or encourage physicians to prescribe the 300 mg dose specifically for patients who are known CYP2D6 poor metabolizers. ¶¶79, 81 col. 9:62-63
  • Identified Points of Contention:
    • Scope Questions: The central dispute will likely concern the content of the Defendants' proposed product label. The key question is whether the label's instructions for using the 300 mg dosage form will "encourage, recommend, or promote" its administration to patients identified as "CYP2D6 poor metabolizers," as required to prove inducement of infringement.
    • Technical Questions: A factual question for the court will be a direct comparison of the proposed label's text with the method steps recited in the asserted claims. The analysis will focus on whether the label's language is a direct instruction to perform the claimed method or if it provides sufficient ambiguity for Defendants to argue they do not induce infringement of all claim elements.

V. Key Claim Terms for Construction

  • The Term: "adjusted dose"

    • Context and Importance: This term is central to the patent's novelty. The infringement case may depend on whether Defendants' standard 300 mg product, when prescribed to a poor metabolizer, is considered an "adjusted dose." Practitioners may focus on this term because Defendants could argue that their product label merely offers a 300 mg dosage option, not an "adjustment" from another dose, thereby attempting to design around the claim.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification defines the adjustment functionally, stating the goal is to administer a dose that is, for example, "about 75%" of the amount recommended for a patient with normal enzyme function (’087 Patent, col. 4:54-58). This supports a construction based on the resulting therapeutic effect and relative amount, rather than a specific numerical reduction.
      • Evidence for a Narrower Interpretation: The patent provides a specific example where a recommended 400 mg dose is reduced to 300 mg for a poor metabolizer (’087 Patent, col. 5:19-29). This could support an argument that "adjusted dose" requires a specific act of reduction from a higher standard dose, rather than simply selecting a lower dose from available options.

  • The Term: "patient is a CYP2D6 poor metabolizer"

    • Context and Importance: This limitation defines the specific patient population to which the claimed method applies. Infringement requires that the accused product's label instructs use in this particular group. The precision of this definition will be critical.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification describes these patients functionally as having "little or no CYP2D6... enzyme function" and a "substantially reduced ability to metabolize aripiprazole" (’087 Patent, col. 3:38-43). This language may support a more general, qualitative definition.
      • Evidence for a Narrower Interpretation: The patent also provides quantitative context, noting that such patients "may have about an about 63-112% increase in aripiprazole exposure (an average of about 80%)" (’087 Patent, col. 3:45-47). A party could argue this language requires a specific, measurable pharmacokinetic outcome to qualify a patient as a "poor metabolizer" under the claims.

VI. Other Allegations

  • Indirect Infringement: The complaint's central theory is induced infringement under 35 U.S.C. § 271(b). It alleges that Defendants, with knowledge of the ’087 Patent, will cause infringement by third parties (healthcare professionals) by providing a product with a package insert that instructs them to administer the generic drug in a manner that practices the patented method (Compl. ¶¶80-81). Knowledge of the patent is alleged based on Defendants' "Third Notice Letter" containing a Paragraph IV certification against the patent (Compl. ¶76).
  • Willful Infringement: The complaint does not use the term "willful," but it requests a finding that the case is "exceptional" and an award of attorney fees and costs, which is the remedy for willful infringement or other litigation misconduct (Compl., Prayer for Relief ¶F). The factual basis for this claim is the allegation that Defendants' infringement will continue despite having actual knowledge of the ’087 Patent.

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

  1. A central issue will be one of induced infringement: Does the precise language of the Defendants' proposed product label, submitted in its ANDA, actively instruct or encourage physicians to administer the 300 mg dose of generic aripiprazole specifically to the patient population defined as "CYP2D6 poor metabolizers," thereby meeting all limitations of the asserted method claims?

  2. The case may also turn on a question of definitional scope: Will the term "adjusted dose" be construed to mean any dose that is functionally appropriate for a poor metabolizer (such as selecting a 300 mg dose), or will it be limited to requiring a specific, articulated reduction from a higher, standard dose (e.g., from 400 mg down to 300 mg)? The outcome of this claim construction could determine whether Defendants' label falls within the scope of the claims.