DCT

3:25-cv-00898

Intra Cellular Therapies Inc v. Zydus Pharma USA Inc

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:25-cv-00898, D.N.J., 01/31/2025
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Zydus Pharmaceuticals (USA) Inc. is a New Jersey corporation with its principal place of business in the state, and Defendant Zydus Lifesciences Ltd. 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 the drug CAPLYTA® (lumateperone) constitutes an act of infringement of four U.S. patents covering methods of using the drug.
  • Technical Context: The technology relates to pharmaceutical methods of using a class of compounds known as heterocycle fused gamma-carbolines for treating central nervous system disorders, including schizophrenia, sleep disorders, and bipolar disorder.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, prompted by a "Second Notice Letter" from Zydus regarding its ANDA filing. The complaint notes that this is the latest in a series of lawsuits filed by the Plaintiff against the same Defendants concerning other patents related to the CAPLYTA® product, with prior cases having been consolidated.

Case Timeline

Date Event
2008-05-27 Earliest Priority Date (RE '’839' Patent)
2013-12-03 Earliest Priority Date ('’227', '’009', '’951' Patents)
2018-05-01 Issue Date (U.S. Patent No. 9,956,227)
2021-03-30 Issue Date (U.S. Patent No. 10,960,009)
2021-06-08 Issue Date (U.S. Patent No. 11,026,951)
2021-12-07 Issue Date (U.S. Reissue Patent No. RE48,839)
2024-02-12 Zydus's First Notice Letter to Plaintiff
2024-03-28 Plaintiff files first related lawsuit against Zydus
2024-08-29 Plaintiff files second related lawsuit against Zydus
2024-11-01 Plaintiff files third related lawsuit against Zydus
2024-12-18 Zydus's Second Notice Letter to Plaintiff
2025-01-31 Complaint Filing Date

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

U.S. Reissue Patent No. RE48,839

  • Patent Identification: RE48,839, “Methods and Compositions for Sleep Disorders and Other Disorders,” issued December 7, 2021.

The Invention Explained

  • Problem Addressed: The patent describes the need for improved treatments for sleep disorders, noting that existing medications like benzodiazepines can cause dependency and other hypnotics can produce undesirable side effects (RE ’839 Patent, col. 2:30-65).
  • The Patented Solution: The invention is a method of treating sleep and other disorders by administering a specific class of compounds (heterocycle fused gamma-carbolines) in a dose that "selectively blocks the 5-HT2A receptor" (RE ’839 Patent, col. 4:1-3). This selective antagonism is purported to improve sleep maintenance and normalize sleep architecture without the side effects associated with less selective drugs (RE ’839 Patent, Abstract; col. 1:49-65).
  • Technical Importance: This approach provided a therapeutic strategy for insomnia that targeted a specific serotonin receptor pathway implicated in sleep regulation, potentially avoiding the known drawbacks of other drug classes (RE ’839 Patent, col. 2:57-65).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶42).
  • The essential elements of claim 1 are:
    • A method for treating one or more 5-HT2A-related disorders.
    • The method comprises administering a specific compound of "Formula I" or its salt form.
    • The compound is administered in a dose that "selectively blocks the 5-HT2A receptor."
  • The complaint alleges infringement of "one or more claims" of the patent, reserving the right to assert others (Compl. ¶41).

U.S. Patent No. 9,956,227

  • Patent Identification: 9,956,227, “Method for the Treatment of Residual Symptoms of Schizophrenia,” issued May 1, 2018.

The Invention Explained

  • Problem Addressed: The patent's background section explains that while conventional antipsychotics are often effective against "positive" symptoms of schizophrenia (e.g., hallucinations), they are largely inadequate for treating the persistent "residual" or "negative" symptoms like social withdrawal, apathy, and cognitive deficits, which hinder patient recovery (’227 Patent, col. 1:53-65).
  • The Patented Solution: The invention claims a method for specifically treating these residual symptoms by administering a compound of "Formula I" to a patient after their acute symptoms have already been treated with an antipsychotic agent (’227 Patent, col. 2:40-44). The method's success is defined by a significant improvement on the "Prosocial PANSS Factor," a clinical scale for measuring social function (’227 Patent, col. 18:7-14).
  • Technical Importance: The invention claims a targeted second-line therapy for the debilitating negative and cognitive symptoms of schizophrenia that often prevent patients from social and occupational reintegration, addressing a significant unmet need in psychiatric care (’227 Patent, col. 1:60-2:2).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶68).
  • The essential elements of claim 1 are:
    • A method for treating residual symptoms of schizophrenia as defined in the PANSS scale.
    • The method comprises administering a compound of "Formula I" or its salt form.
    • Administration occurs "after treatment of acute symptoms of schizophrenia with an antipsychotic agent."
    • The treatment results in the patient "significantly improv[ing] on the Prosocial PANSS Factor change from baseline."
  • The complaint alleges infringement of "one or more claims," reserving the right to assert others (Compl. ¶67).

Multi-Patent Capsule: U.S. Patent No. 10,960,009

  • Patent Identification: 10,960,009, “Methods of Treating Schizophrenia and Depression,” issued March 30, 2021 (Compl. ¶86).
  • Technology Synopsis: This patent addresses the treatment of negative symptoms in schizophrenic patients, particularly those with co-morbid depression (’009 Patent, col. 1:43-2:2). The patented solution is a method of treating these negative symptoms by administering a specific compound of Formula I within a defined dosage range of 40 mg to 60 mg per day (’009 Patent, col. 18:31-41).
  • Asserted Claims: The complaint exemplifies independent claim 1 (Compl. ¶94).
  • Accused Features: The complaint alleges that Zydus’s proposed product label will direct the administration of lumateperone for treating negative symptoms of schizophrenia in a 40 mg to 60 mg daily dose (Compl. ¶95).

Multi-Patent Capsule: U.S. Patent No. 11,026,951

  • Patent Identification: 11,026,951, “Methods of Treating Bipolar Disorder,” issued June 8, 2021 (Compl. ¶112).
  • Technology Synopsis: This patent addresses the treatment of bipolar I and/or bipolar II disorders (’951 Patent, col. 2:1-4). The claimed invention is a method of treating these disorders by administering a specific compound of Formula I as a monotherapy, meaning it is "not used in combination with another antipsychotic agent" (’951 Patent, col. 9:25-34).
  • Asserted Claims: The complaint exemplifies independent claim 1 (Compl. ¶119).
  • Accused Features: The complaint alleges that Zydus’s proposed product label will direct the use of lumateperone for treating bipolar disorder without requiring combination with another antipsychotic agent (Compl. ¶120).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is "Zydus's ANDA Product," identified as a generic version of CAPLYTA® (lumateperone) capsules intended for marketing in 10.5 mg, 21 mg, and 42 mg strengths (Compl. ¶¶1, 29). The act of infringement cited under the Hatch-Waxman Act is Zydus's submission of Abbreviated New Drug Application No. 218652 to the FDA (Compl. ¶2).
  • Functionality and Market Context: The product contains the active pharmaceutical ingredient lumateperone, which is approved for the treatment of schizophrenia and depressive episodes associated with bipolar disorder (Compl. ¶28). The complaint alleges that Zydus seeks FDA approval to market this product as a generic equivalent to Plaintiff's branded CAPLYTA® before the expiration of the patents-in-suit (Compl. ¶¶1, 32). The infringement theory is based not on the product itself, but on the intended use for which Zydus is seeking approval, as would be described in its proposed product labeling (Compl. ¶¶41, 67, 93, 118). The complaint provides a chemical structure of a "Compound of Formula I," which it alleges includes lumateperone, as a key visual element for each asserted patent (Compl. ¶¶42, 68, 94, 119).

IV. Analysis of Infringement Allegations

RE48,839 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for the treatment of one or more 5-HT2A-related disorders... The proposed label for Zydus's ANDA Product will allegedly direct its use for treating 5-HT2A-related disorders. ¶43 col. 1:49-53
comprising administering to a patient in need thereof a Compound of Formula I... Zydus's ANDA Product contains lumateperone, which the complaint alleges is a Compound of Formula I. The complaint includes a diagram of Formula I's chemical structure (Compl. ¶42). ¶¶40, 43 col. 3:20-45
in a dose which selectively blocks the 5-HT2A receptor. The proposed label will allegedly direct administration in a dose that selectively blocks the 5-HT2A receptor. ¶43 col. 4:1-3

9,956,227 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for the treatment of residual symptoms of schizophrenia as defined in the Positive and Negative Syndrome Scale (PANSS) for Schizophrenia... Zydus's proposed label will allegedly direct the use of its product to treat residual symptoms of schizophrenia. ¶69 col. 1:17-25
comprising administering to a patient in need thereof, after treatment of acute symptoms of schizophrenia with an antipsychotic agent... The proposed label will allegedly instruct physicians to administer the product after a patient's acute schizophrenic symptoms have been treated. ¶69 col. 2:40-44
an effective amount of a compound of Formula I... Zydus's ANDA Product contains lumateperone, which the complaint alleges is a compound of Formula I. The complaint provides a chemical structure diagram for Formula I (Compl. ¶68). ¶¶66, 69 col. 3:17-48
wherein the patient significantly improves on the Prosocial PANSS Factor change from baseline. The complaint alleges that use as directed by the proposed label would involve treating residual symptoms, which would result in the claimed improvement. ¶69 col. 18:7-14
  • Identified Points of Contention:
    • Scope Questions: In this ANDA litigation, a central issue will be whether the specific instructions and indications in Zydus’s proposed product label will be found to encourage, recommend, or promote the specific methods recited in the claims. For the ’227 Patent, this raises the question of whether the label instructs administration specifically for "residual symptoms" after acute-phase treatment. For the ’951 Patent, the question is whether the label instructs use as a monotherapy.
    • Technical Questions: For the RE ’839 Patent, a key technical question will be how the term "selectively blocks" is defined and whether the dosages on the Zydus label meet that definition. For the ’227 Patent, the "wherein the patient significantly improves" clause raises the question of whether this is a required step of the method that Zydus induces, or merely a statement of intended result.

V. Key Claim Terms for Construction

For the RE '839 Patent

  • The Term: "a dose which selectively blocks the 5-HT2A receptor"
  • Context and Importance: This term defines the operative dosage of the claimed method. The infringement analysis will depend on whether the dosages included in Zydus's proposed labeling are construed as falling within the scope of a "selective" dose. Practitioners may focus on this term because its construction could determine whether standard therapeutic doses infringe, or if the claim is limited to a narrower, low-dose regimen with negligible activity at other receptors.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification states that at low doses, the compounds "may be used to selectively antagonize 5-HT2A receptors," which may suggest selectivity is a primary, rather than exclusive, effect at those doses (RE ’839 Patent, col. 4:1-3).
    • Evidence for a Narrower Interpretation: The patent's background distinguishes the invention from prior art drugs by noting their undesirable side effects, which are often linked to non-selective receptor activity (e.g., at dopamine receptors) (RE ’839 Patent, col. 2:30-65). This context could support an interpretation where "selectively" requires minimal or no clinically significant activity at other receptors.

For the '227 Patent

  • The Term: "residual symptoms of schizophrenia"
  • Context and Importance: This phrase is the subject of the claimed treatment method and is critical for determining the scope of infringement. The dispute will likely center on whether the indications on Zydus's proposed label are for treating schizophrenia generally or if they specifically describe or encourage treatment of the "residual" phase as defined by the patent.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification defines residual symptoms by referencing symptoms from the PANSS clinical scale and by describing them generally as negative symptoms, social withdrawal, and cognitive dysfunction (’227 Patent, col. 1:53-65). A party could argue that any label indication for treating these types of symptoms falls within the claim's scope.
    • Evidence for a Narrower Interpretation: The specification consistently frames "residual symptoms" as those that persist "after the active phase symptoms have subsided" and notes the claimed method occurs "after treatment of acute symptoms" (’227 Patent, col. 1:47-52, Claim 1). This explicit temporal and symptomatic sequence could support a narrower construction requiring the label to instruct this specific treatment context.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement of infringement across all asserted patents. The factual basis is the allegation that Zydus’s proposed product labeling will instruct physicians and patients to administer the ANDA product in a manner that directly infringes the claimed methods (Compl. ¶¶49, 75, 101, 126). The complaint also alleges contributory infringement, asserting that Zydus's product is not a staple article of commerce and is especially made for an infringing use, for which there is no substantial non-infringing use (Compl. ¶¶50, 76, 102, 127).
  • Willful Infringement: The complaint alleges that Zydus has acted with "full knowledge" of the patents-in-suit and "without a reasonable basis for believing that it would not be liable for infringement" (Compl. ¶¶53, 79, 105, 130). This allegation is based on Zydus's knowledge of the patents, evidenced by its Paragraph IV certifications and notice letters sent to the Plaintiff prior to the lawsuit (Compl. ¶¶6, 31, 39, 65).

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

  • A core issue will be one of label interpretation: will the court find that the language of Zydus’s proposed product label directly instructs or otherwise implicitly encourages physicians to perform the specific methods recited in the claims, such as treating "residual symptoms" after an acute phase ('227 Patent), using a "selective" dose ('RE '839 Patent), or administering the drug as a monotherapy ('951 Patent)?
  • A second central issue will be one of claim scope: can the term "a dose which selectively blocks the 5-HT2A receptor" (RE '839 Patent) be construed to encompass the dosages included on the Zydus label for general therapeutic use, or will the patent's own description limit the term to a narrower, low-dose range where off-target effects are negligible?
  • A key evidentiary question will be one of induced infringement: for method claims that recite a clinical outcome, such as the patient "significantly improv[ing] on the Prosocial PANSS Factor" ('227 Patent), what evidence beyond the label itself is required to establish that Zydus possessed the specific intent to cause this result, as opposed to merely intending the sale of its product for a general therapeutic indication?