DCT

3:24-cv-08856

Intra Cellular Therapies Inc v. Zydus Pharma USA Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:24-cv-08856, D.N.J., 08/29/2024
  • Venue Allegations: Venue is alleged to be proper as to Zydus Pharmaceuticals (USA) Inc. because it is a New Jersey corporation with its principal place of business in the district. Venue is alleged to be proper as to Zydus Lifesciences Ltd. on the basis that it is subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of Plaintiff's CAPLYTA® (lumateperone) drug constitutes an act of infringement of two recently issued patents.
  • Technical Context: The technology concerns pharmaceutical methods and compositions for lumateperone, an atypical antipsychotic used for the treatment of schizophrenia and bipolar depression.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, prompted by a notice letter from Zydus informing the Plaintiff of its ANDA filing and its certification that Plaintiff's patents are invalid, unenforceable, or not infringed. The complaint notes that this is a follow-on suit to prior litigation between the parties involving other patents covering CAPLYTA®.

Case Timeline

Date Event
2018-03-16 '617 Patent Priority Date
2018-12-14 '459 Patent Priority Date
2024-02-12 Zydus sends Notice Letter to Plaintiff
2024-03-28 Plaintiff files prior lawsuit against Zydus
2024-05-14 '617 Patent Issue Date
2024-08-27 '459 Patent Issue Date
2024-08-29 Complaint Filing Date

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

U.S. Patent No. 11,980,617 - "Methods of Treating Acute Depression and/or Acute Anxiety"

  • Patent Identification: U.S. Patent No. 11,980,617, "Methods of Treating Acute Depression and/or Acute Anxiety," issued May 14, 2024 (Compl. ¶30).

The Invention Explained

  • Problem Addressed: The patent identifies a need for rapid-acting antidepressants, noting that conventional treatments like SSRIs often take weeks to achieve full effect, which is suboptimal for patients in acute distress (’617 Patent, col. 3:7-18). While ketamine offers a rapid-acting alternative, it has significant side effects, requires non-oral administration, and carries a risk of abuse (’617 Patent, col. 3:36-44).
  • The Patented Solution: The invention is a method for the acute treatment of depression and/or anxiety by administering lumateperone. The patent posits that lumateperone provides a fast-acting antidepressant effect through a mechanism involving the enhancement of NMDA and AMPA currents, paralleling the fast-acting pathway of ketamine but without its adverse side effects, making it suitable for oral administration (’617 Patent, Abstract; col. 4:46-65).
  • Technical Importance: The invention claims to provide an orally-available treatment that can alleviate symptoms of acute depression within hours or days, addressing a significant unmet need in psychiatric care (’617 Patent, col. 4:38-41, 60-65).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶37).
  • The essential elements of claim 1 are:
    • A method of treating acute depression and/or acute anxiety,
    • comprising administering to a patient in need thereof,
    • a therapeutically effective amount of a Compound of Formula I (lumateperone) or its pharmaceutically acceptable salt.
  • The complaint alleges infringement of "one or more claims," reserving the right to assert others (Compl. ¶36).

U.S. Patent No. 12,070,459 - "Pharmaceutical Capsule Compositions Comprising Lumateperone Mono-Tosylate"

  • Patent Identification: U.S. Patent No. 12,070,459, "Pharmaceutical Capsule Compositions Comprising Lumateperone Mono-Tosylate," issued August 27, 2024 (Compl. ¶55).

The Invention Explained

  • Problem Addressed: The patent background describes the therapeutic profile of lumateperone but does not explicitly state a problem with its formulation (’459 Patent, col. 1:33-2:4). The technical challenge implicitly addressed is the creation of a stable, oral dosage form that achieves specific, desirable pharmacokinetic (PK) properties.
  • The Patented Solution: The invention is a specific pharmaceutical capsule composition containing lumateperone mono-tosylate in a solid crystal form. The claims define the composition by the amount of active ingredient, its percentage weight in a blend with specific excipients, and, critically, by the specific PK profile (e.g., Cmax, Tmax, and AUC) that results from administering a single capsule under fasting conditions (’459 Patent, Abstract; col. 18:1-32).
  • Technical Importance: Achieving a predictable and optimized pharmacokinetic profile is essential for the safety and efficacy of a drug, especially for psychiatric medications where the therapeutic window can be narrow.

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶62).
  • The essential elements of claim 1 are:
    • A pharmaceutical capsule for oral administration comprising lumateperone mono-tosylate in solid crystal form.
    • The capsule comprises "about 60 mg" of the active ingredient.
    • The capsule comprises a blend of 10% to 30% by weight of the active ingredient with one or more specified carriers.
    • Administration under fasting conditions provides a specified maximal plasma concentration (Cmax), time to maximal concentration (Tmax), and/or area under the curve (AUC).
  • The complaint alleges infringement of "one or more claims" (Compl. ¶64).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is "Zydus’s ANDA Product," which is a proposed generic version of CAPLYTA® (lumateperone) capsules in 10.5 mg, 21 mg, and 42 mg dosage strengths (Compl. ¶¶1, 26).

Functionality and Market Context

The Zydus ANDA Product contains lumateperone and is intended to be a generic substitute for Plaintiff's branded drug, CAPLYTA®, which is approved for treating schizophrenia and bipolar depression (Compl. ¶¶25, 26). The complaint alleges that Zydus's ANDA includes bioequivalence studies to demonstrate its product is a generic version of CAPLYTA® (Compl. ¶26). Zydus is seeking FDA approval to manufacture, use, and sell this product in the United States prior to the expiration of the patents-in-suit (Compl. ¶28). The chemical structure of the active ingredient, lumateperone, is depicted in the complaint as part of the recited claim language for both asserted patents (Compl. p. 9, p. 12).

IV. Analysis of Infringement Allegations

'617 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating acute depression and/or acute anxiety, The proposed labeling for Zydus's ANDA Product will direct its use for treating acute depression and/or acute anxiety. ¶38 col. 45:7-9
comprising administering to a patient in need thereof, a therapeutically effective amount of a Compound of Formula I...in free, or pharmaceutically acceptable salt form. Zydus's ANDA Product contains lumateperone (Compound of Formula I) and its proposed label will instruct administration of a therapeutically effective dose. ¶¶35, 38 col. 2:5-15

Identified Points of Contention

  • Scope Questions: A central dispute may be whether the indications for use on Zydus's proposed product label fall within the scope of the claim term "acute depression and/or acute anxiety." The infringement theory rests on the content of a label that is not yet public, and its interpretation will depend on the construction of "acute" as defined in the patent (’617 Patent, col. 35:36-44, col. 36:1-10).
  • Technical Questions: The factual question for the court will be whether the language of Zydus's proposed label actively instructs or encourages physicians and patients to perform the claimed method of treatment, which is a key element for induced infringement.

'459 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical capsule for oral administration, comprising lumateperone...in mono-tosylate salt form, wherein the lumateperone mono-tosylate is in solid crystal form... Zydus's ANDA Product is a pharmaceutical capsule for oral administration that contains lumateperone mono-tosylate in solid crystal form. ¶63 col. 18:1-12
wherein the capsule comprises the lumateperone mono-tosylate in an amount of about 60 mg...and wherein the capsule comprises a blend of 10 to 30% by weight of lumateperone... The Zydus ANDA Product is allegedly a pharmaceutical capsule that meets the formulation requirements of claim 1 related to the amount and weight percentage of the active ingredient. ¶63 col. 18:13-22
and wherein administration of an oral dose of a single capsule under fasting conditions provides a maximal plasma concentration...of 15-55 ng/mL, and/or a time to maximal plasma concentration...of 0.7 to 1.5 hours, and/or an area under the plasma concentration curve...of 51 to 135 hours-ng/mL. Administration of a single capsule of the Zydus ANDA Product under fasting conditions will allegedly result in the specific pharmacokinetic profile recited in the claim. ¶63 col. 18:23-32

Identified Points of Contention

  • Scope Questions: A primary dispute will likely concern the claim limitation "about 60 mg." Since the accused products are offered in 10.5 mg, 21 mg, and 42 mg dosages, the infringement analysis raises the question of whether any of these amounts can be considered "about 60 mg" (Compl. ¶¶26, 62).
  • Technical Questions: The infringement case hinges on evidence from Zydus's ANDA. A key factual question will be whether the bioequivalence data for any of Zydus's product strengths demonstrates the specific pharmacokinetic profile (Cmax, Tmax, and AUC) required by claim 1.

V. Key Claim Terms for Construction

'617 Patent Term

  • The Term: "acute depression"
  • Context and Importance: The infringement of claim 1 of the ’617 Patent is based on inducement, which will turn on whether Zydus's proposed label instructs the treatment of a condition that falls within the scope of "acute depression." Practitioners may focus on this term because the branded drug is approved for broader conditions like bipolar depression, and the case will depend on whether that approved use overlaps with the patent’s definition of "acute."
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent states that the term "may thus refer to the initial period of a major depressive episode, a short-duration depressive episode, or a recurrent brief depressive episode," directly linking it to established clinical diagnoses (’617 Patent, col. 35:40-44).
    • Evidence for a Narrower Interpretation: The patent qualifies the term by stating it refers to the "initial period of what may be a brief or a chronic episode of depression," which a defendant could argue limits the term to a specific temporal phase of the illness, potentially excluding general maintenance therapy (’617 Patent, col. 35:36-39).

'459 Patent Term

  • The Term: "about 60 mg"
  • Context and Importance: This term is critical because none of the accused products contain exactly 60 mg of the active ingredient; the highest dosage is 42 mg (Compl. ¶26). Plaintiff's infringement theory requires that at least the 42 mg product falls within the scope of "about 60 mg."
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The use of the word "about" inherently suggests a numerical range rather than an exact value. A plaintiff may argue it is intended to cover dosages that are pharmacokinetically equivalent or achieve the same therapeutic effect.
    • Evidence for a Narrower Interpretation: The patent includes dependent claims that recite other specific dosages, such as 40 mg (e.g., ’459 Patent, claim 27). A defendant may argue that the explicit claiming of other amounts implies that "about 60 mg" should be construed narrowly and does not encompass a dosage as different as 42 mg.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Zydus will actively induce infringement of both patents. For the ’617 Patent, inducement is based on the proposed product labeling allegedly instructing the claimed method of treating acute depression/anxiety (Compl. ¶44). For the ’459 Patent, inducement is based on the label instructing the use of the allegedly infringing formulation (Compl. ¶69). For both, the complaint alleges Zydus acts with knowledge of the patents and specific intent to infringe (Compl. ¶¶44, 69).
  • Willful Infringement: The complaint alleges willful infringement of both patents, asserting that Zydus acted with full knowledge of the patents and "without a reasonable basis for believing that it would not be liable for infringement" (Compl. ¶¶48, 73).

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

  • A core issue will be one of claim scope and label interpretation: for the ’617 patent, can the term "acute depression," as defined in the specification, be construed to read on the indications for use that will be described in Zydus's proposed product label for its generic version of a drug approved to treat bipolar depression and schizophrenia?
  • A key evidentiary question will be one of technical and definitional scope: for the ’459 patent, does the claim term "about 60 mg" encompass Zydus's 42 mg product, and will the undisclosed bioequivalence data in Zydus’s ANDA demonstrate that its product meets the specific pharmacokinetic limitations of the asserted claim?
  • Ultimately, the dispute will likely turn on the specific contents of Zydus's confidential ANDA filing—namely, the proposed label and the underlying bioequivalence data—which will serve as the primary evidence for the infringement analysis of both patents-in-suit.