DCT

3:24-cv-04264

Intra Cellular Therapies Inc v. Aurobindo Pharma Ltd

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Key Events
Amended Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:24-cv-04264, D.N.J., 11/03/2025
  • Venue Allegations: Venue is alleged as proper in the District of New Jersey because Zydus Pharmaceuticals (USA) Inc. is a New Jersey corporation with its principal place of business in the district, and its parent company, Zydus Lifesciences Ltd., is subject to personal jurisdiction there.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA, seeking to market a generic version of Plaintiff's CAPLYTA® (lumateperone) product, constitutes an act of infringement of six U.S. patents.
  • Technical Context: The patents relate to pharmaceutical compounds and methods for treating central nervous system disorders such as schizophrenia, bipolar disorder, and sleep disorders.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendants’ (collectively "Zydus") submission of ANDA No. 218652. Zydus provided Plaintiff with notice letters on February 12, 2024, and December 18, 2024, which included Paragraph IV certifications asserting that the asserted patents are invalid, unenforceable, and/or not infringed by Zydus's proposed generic product. The present action is a consolidated case, combining several prior lawsuits filed by the Plaintiff against Zydus concerning the same ANDA but different sets of patents.

Case Timeline

Date Event
2008-05-27 RE '839 Patent Priority Date
2013-12-03 '227, '009, '951 Patents Priority Date
2018-05-01 U.S. Patent No. 9,956,227 Issued
2021-03-30 U.S. Patent No. 10,960,009 Issued
2021-06-08 U.S. Patent No. 11,026,951 Issued
2021-12-07 U.S. Reissue Patent No. RE48,839 Issued
2024-02-12 Zydus's First Notice Letter to Plaintiff
2024-03-28 Plaintiff files initial consolidated lawsuit against Zydus
2024-12-18 Zydus's Second Notice Letter to Plaintiff
2025-01-31 Plaintiff files lawsuit that is subject of current amendment
2025-09-09 U.S. Patent No. 12,409,176 Issued
2025-09-09 U.S. Patent No. 12,410,195 Issued
2025-11-03 First Amended Complaint Filed

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

U.S. Reissue Patent No. RE48,839 - "Methods and Compositions for Sleep Disorders and Other Disorders"

The Invention Explained

  • Problem Addressed: The patent background describes a need for novel compounds to treat central nervous system disorders associated with serotonin (5-HT2A) receptor modulation, such as anxiety, depression, psychosis, and sleep disorders (RE48839 Patent, col. 1:29-36).
  • The Patented Solution: The invention provides methods of using a class of compounds known as substituted heterocycle fused gamma-carbolines to treat these disorders. The core compound, lumateperone, is described as a novel therapeutic agent with potent 5-HT2A receptor antagonism and specific dopamine receptor modulating properties (RE48,839 Patent, col. 2:16-25). The patent claims a method of treating 5-HT2A-related disorders by administering a compound of a specific chemical structure (Formula I) in a dose that "selectively blocks the 5-HT2A receptor" (RE48,839 Patent, col. 9:66-10:14).
  • Technical Importance: The invention provided a therapeutic approach with a novel pharmacological profile, combining potent 5-HT2A antagonism with dopamine modulation, aiming to treat CNS disorders with potentially different efficacy or side-effect profiles compared to existing treatments (RE48,839 Patent, col. 2:16-25).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶ 43).
  • Claim 1 of the RE ’839 Patent contains the following essential elements:
    • A method for the treatment of one or more 5-HT2A-related disorders,
    • comprising administering to a patient a Compound of Formula I,
    • wherein the compound has a specific chemical structure with variable groups X and Y,
    • in a free or pharmaceutically acceptable salt form,
    • in a dose which selectively blocks the 5-HT2A receptor.
  • The complaint alleges infringement of "one or more claims" of the patent (Compl. ¶ 42).

U.S. Patent No. 9,956,227 - "Method for the Treatment of Residual Symptoms of Schizophrenia"

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of treating the "residual phase" of schizophrenia, which is characterized by negative symptoms (e.g., emotional withdrawal), cognitive dysfunction, and insomnia that persist even after the acute "active phase" symptoms (e.g., delusions, hallucinations) have subsided with treatment (’227 Patent, parent U.S. Patent No. 10,960,009, col. 1:50-66). The background notes an "urgent need" for therapies that treat these persistent residual symptoms.
  • The Patented Solution: The patent claims a method for treating these specific residual symptoms. The method involves administering an effective amount of a compound of Formula I (which covers lumateperone) to a patient after they have already been treated for the acute symptoms of schizophrenia. The treatment's success is defined by the patient showing significant improvement on a specific clinical metric, the "Prosocial PANSS Factor" (’227 Patent, col. 10:43-11:5).
  • Technical Importance: This invention targets a specific and difficult-to-treat stage of schizophrenia, aiming to improve social function and quality of life for patients whose acute psychosis is managed but who still suffer from debilitating residual symptoms (’227 Patent, parent U.S. Patent No. 10,960,009, col. 2:1-4).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶ 69).
  • Claim 1 of the ’227 Patent contains the following essential elements:
    • A method for the treatment of residual symptoms of schizophrenia as defined in the PANSS scale,
    • comprising administering to a patient, after treatment of a cute symptoms,
    • an effective amount of a compound of Formula I with a specific chemical structure,
    • in free or pharmaceutically acceptable salt form,
    • wherein the patient significantly improves on the Prosocial PANSS Factor change from baseline.
  • The complaint alleges infringement of "one or more claims" of the patent (Compl. ¶ 68).

U.S. Patent No. 10,960,009 - "Methods of Treating Schizophrenia and Depression"

  • Technology Synopsis: The patent claims a method for treating the negative symptoms of schizophrenia. The solution involves administering a specific compound of Formula I at a dose of 40 mg to 60 mg per day (’009 Patent, col. 39:13-29).
  • Asserted Claims: Independent claim 1 (Compl. ¶ 95).
  • Accused Features: The complaint alleges that the use of Zydus's ANDA Product according to its proposed label would involve administering 40 mg to 60 mg per day of the claimed compound to treat negative symptoms of schizophrenia (Compl. ¶ 96).

U.S. Patent No. 11,026,951 - "Methods of Treating Bipolar Disorder"

  • Technology Synopsis: The patent claims a method for treating bipolar disorder I and/or II. A key aspect of the claimed method is that the compound is used as a monotherapy, specified by the limitation "wherein said Compound is not used in combination with another antipsychotic agent" (’951 Patent, col. 40:20-22).
  • Asserted Claims: Independent claim 1 (Compl. ¶ 120).
  • Accused Features: Plaintiff alleges that the use of Zydus's product as directed by its label would involve administering the compound for bipolar disorder without combination with another antipsychotic agent (Compl. ¶ 121).

U.S. Patent No. 12,409,176 - "Methods of Treating Acute Depression"

  • Technology Synopsis: The patent claims a method for treating acute depression that is specifically a "depressive episode associated with bipolar disorder." The method requires once-daily oral administration of the compound in its tosylate salt form in a capsule or tablet (’176 Patent, parent U.S. Patent No. 11,980,617, col. 29:34-49).
  • Asserted Claims: Independent claim 1 (Compl. ¶ 145).
  • Accused Features: The complaint alleges that Zydus's proposed label would direct the use of its capsule product to treat acute depressive episodes associated with bipolar disorder (Compl. ¶ 146).

U.S. Patent No. 12,410,195 - "Pharmaceutical Compositions Comprising 4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline-8(7H)-yl)-1-(4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)phenyl)butan-1-one for Treating Conditions of the Central Nervous System and Cardiac Disorders"

  • Technology Synopsis: The patent claims a pharmaceutical composition comprising two distinct compounds: Formula I, a metabolite of lumateperone, and Formula II, lumateperone itself (’195 Patent, parent U.S. Patent No. 11,753,419, col. 27:1-32:10).
  • Asserted Claims: Independent claim 1 (Compl. ¶ 170).
  • Accused Features: The complaint alleges that Zydus's ANDA Product is a pharmaceutical composition that comprises both the compound of Formula I and the compound of Formula II (Compl. ¶ 171).

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 strengths (Compl. ¶¶ 1, 30). The act of infringement is the submission of ANDA No. 218652 to the FDA seeking approval to market this product (Compl. ¶¶ 1-2).

Functionality and Market Context

  • The Zydus ANDA Product contains lumateperone as its active pharmaceutical ingredient and is intended for the treatment of schizophrenia and depressive episodes associated with bipolar disorder (Compl. ¶¶ 29, 41, 67). By filing an ANDA with a Paragraph IV certification, Zydus is seeking to enter the market with a generic competitor to Plaintiff's branded drug, CAPLYTA®, prior to the expiration of the Patents-in-Suit (Compl. ¶¶ 31-33).

IV. Analysis of Infringement Allegations

RE '839 Patent 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 complaint alleges that Zydus's proposed product label would direct the product's use for treating one or more 5-HT2A-related disorders. ¶44 col. 2:32-36
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 Formula I compound, and the label directs its administration to patients. The complaint provides a chemical structure diagram of Formula I. (Compl. p. 10). ¶¶41, 44 col. 9:66-10:11
in a dose which selectively blocks the 5-HT2A receptor. The complaint alleges the use of Zydus's product as directed would involve administering a dose that meets this functional limitation. ¶44 col. 2:16-18

Identified Points of Contention

  • Scope Questions: A central question for claim construction may be the meaning of "selectively blocks the 5-HT2A receptor." This functional language could be a point of dispute regarding the degree of selectivity required and how it is measured, especially given lumateperone's known activity at other receptors.
  • Technical Questions: The infringement theory relies on Zydus's proposed label inducing an infringing use. The case may turn on whether the specific instructions and indications for use on Zydus's label will, in practice, lead physicians and patients to perform all steps of the claimed method.

'227 Patent 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... Zydus's proposed label would allegedly direct the treatment of residual symptoms of schizophrenia. ¶70 col. 10:45-46
comprising administering to a patient... after treatment of acute symptoms of schizophrenia with an antipsychotic agent, an effective amount of a compound of Formula I... The product contains lumateperone (a Formula I compound), and the complaint alleges its proposed label would instruct administration after a patient has been treated for acute symptoms. The complaint provides a chemical structure diagram of Formula I. (Compl. p. 14). ¶70 col. 10:48-11:2
wherein the patient significantly improves on the Prosocial PANSS Factor change from baseline. The complaint alleges that using the Zydus product in accordance with its label would result in this specific clinical outcome. ¶70 col. 11:3-5

Identified Points of Contention

  • Scope Questions: The definition of "residual symptoms of schizophrenia" will be critical. The claim ties this term to the PANSS scale, which may create a focal point for arguments about whether the indications on Zydus's label meet this specific definition.
  • Technical Questions: A key evidentiary question will be whether the use of the generic product as directed by its proposed label can be proven to necessarily result in the claimed outcome of a "significant[] improve[ment] on the Prosocial PANSS Factor." Proving that a particular clinical outcome will inevitably follow from instructions on a label is a common challenge in Hatch-Waxman litigation over method-of-treatment claims.

V. Key Claim Terms for Construction

  • The Term: "selectively blocks the 5-HT2A receptor" (from RE ’839 Patent, Claim 1)
    • Context and Importance: This functional limitation is central to defining the claimed method. Practitioners may focus on this term because its construction will determine the required pharmacological activity of an infringing product. The dispute may center on whether "selectively" implies a specific ratio of activity at the 5-HT2A receptor versus other receptors (e.g., dopamine D2, SERT) and whether Zydus's proposed product meets that standard.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent specification discloses that lumateperone has activity at multiple receptors, including dopamine D1/D2 and the serotonin transporter (SERT) (RE48,839 Patent, col. 2:16-25). This could support an interpretation where "selectively" does not mean exclusively, but rather designates the 5-HT2A receptor as a primary or potent target among others.
      • Evidence for a Narrower Interpretation: The specification highlights the "potent (Ki=0.5 nM) 5-HT2A receptor antagonism" as a key feature (RE48,839 Patent, col. 2:16-18). It also describes "differential dose-dependent effects, selectively targeting the 5-HT2A receptor at low doses" (RE48,839 Patent, col. 2:64-67). This language could support a narrower construction tied to a high degree of preference for the 5-HT2A receptor, particularly at the claimed therapeutic dosage.
  • The Term: "residual symptoms of schizophrenia" (from ’227 Patent, Claim 1)
    • Context and Importance: This term defines the specific condition being treated and thus the scope of the method claim. Practitioners may focus on this term because infringement will depend on whether Zydus's proposed label instructs treatment for this particular phase of the illness, as opposed to schizophrenia generally or its acute symptoms.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The background section of the patent family describes residual symptoms broadly to include "negative symptoms such as emotional withdrawal... and symptoms of general psychopathology including active social avoidance, anxiety, tension, and somatic concerns" (’227 Patent, parent U.S. Patent No. 10,960,009, col. 1:55-60). This could support a more general clinical understanding of the term.
      • Evidence for a Narrower Interpretation: The claim explicitly states "residual symptoms of schizophrenia as defined in the Positive and Negative Syndrome Scale (PANSS)" and further requires that the patient "significantly improves on the Prosocial PANSS Factor" (’227 Patent, col. 10:45-46, 11:3-5). This language may be used to argue that the term is strictly limited to the specific clinical parameters and scoring methodologies of the PANSS instrument itself, rather than a broader clinical diagnosis.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Zydus will actively induce infringement because its proposed product labeling will instruct physicians and patients to administer the generic drug in a manner that practices the steps of the patented methods (Compl. ¶¶ 50, 76). The complaint also pleads contributory infringement, alleging Zydus's product and its labeling are "especially made or adapted for use" in an infringing manner and are "not suitable for substantial noninfringing use" (Compl. ¶¶ 51, 77).
  • Willful Infringement: The complaint alleges that Zydus has acted with "full knowledge" of the Patents-in-Suit and without a reasonable basis for believing it would not be liable for infringement (Compl. ¶¶ 54, 80). This allegation is based on Zydus's knowledge of the patents through the Hatch-Waxman notice process and its continued pursuit of FDA approval for its generic product.

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

  • A core issue will be one of induced infringement: for the multiple method-of-treatment claims, can Plaintiff demonstrate that the language on Zydus's proposed product label will inevitably lead physicians to prescribe, and patients to use, the generic product in a way that practices every step of the claimed methods? This includes specific limitations such as treating "residual symptoms" after acute treatment ('227 Patent) or use as a "monotherapy" ('951 Patent).
  • A key technical question will be one of functional equivalence: Does the administration of Zydus's product, according to its proposed label, achieve the specific functional outcomes required by the claims, such as "selectively block[ing] the 5-HT2A receptor" (RE '839 Patent) or causing a "significant[] improve[ment] on the Prosocial PANSS Factor" ('227 Patent)?
  • A central question of direct infringement will arise for the composition claim in the '195 patent: does Zydus's ANDA product, as a factual matter, contain both the lumateperone metabolite (Formula I) and lumateperone itself (Formula II), as required by the claim?