DCT

3:24-cv-04264

Intra Cellular Therapies Inc v. Aurobindo Pharma Ltd

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:24-cv-04264, D.N.J., 03/27/2024
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Aurobindo Pharma USA, Inc. has its principal place of business in the state, and Defendant Aurobindo Pharma Ltd. is subject to personal jurisdiction in the district through its own and its subsidiary's business activities.
  • 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) product constitutes an act of infringement of eight U.S. patents covering the drug's composition, methods of use, and specific treatment regimens.
  • Technical Context: The patents relate to lumateperone, an atypical antipsychotic drug approved for treating schizophrenia and bipolar depression, which acts on serotonin and dopamine pathways in the central nervous system.
  • Key Procedural History: This action was commenced under the Hatch-Waxman Act within 45 days of Plaintiff receiving a "Notice Letter" from Aurobindo, dated February 12, 2024. In the letter, Aurobindo provided Paragraph IV certifications alleging that the patents-in-suit are invalid, unenforceable, and/or will not be infringed by its proposed generic product.

Case Timeline

Date Event
2008-05-27 Earliest Priority Date for U.S. Patent RE48,839
2013-12-03 Earliest Priority Date for U.S. Patents 9,956,227; 10,960,009; 11,026,951
2018-05-01 Issue Date for U.S. Patent 9,956,227
2018-08-31 Earliest Priority Date for U.S. Patents 10,695,345; 11,690,842; 11,806,348
2019-12-11 Earliest Priority Date for U.S. Patent 11,753,419
2020-06-30 Issue Date for U.S. Patent 10,695,345
2021-03-30 Issue Date for U.S. Patent 10,960,009
2021-06-08 Issue Date for U.S. Patent 11,026,951
2021-12-07 Issue Date for U.S. Patent RE48,839
2023-07-04 Issue Date for U.S. Patent 11,690,842
2023-09-12 Issue Date for U.S. Patent 11,753,419
2023-11-07 Issue Date for U.S. Patent 11,806,348
2024-02-12 Aurobindo sends Notice Letter to Plaintiff regarding ANDA filing
2024-03-27 Complaint Filing Date

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

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

  • Issued: December 7, 2021

The Invention Explained

  • Problem Addressed: The patent addresses central nervous system disorders associated with serotonin 5-HT2A receptor modulation, such as anxiety, psychosis, schizophrenia, and sleep disorders (RE '839 Patent, col. 1:29-37).
  • The Patented Solution: The invention is a method of treating these 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, Claim 1). The specification describes these compounds as having dose-dependent effects, targeting the 5-HT2A receptor at lower doses while progressively interacting with dopamine receptors at higher doses, which allows for different therapeutic effects depending on the dosage (RE '839 Patent, col. 2:61-col. 3:3).
  • Technical Importance: This dose-selective approach suggests a way to treat certain disorders without the side effects associated with broader receptor activity, particularly the effects of modulating dopamine receptors which are implicated in antipsychotic medications.

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶41).
  • Claim 1 requires:
    • A method for the treatment of one or more 5-HT2A-related disorders,
    • comprising administering to a patient in need thereof a Compound of Formula I (or its salt form),
    • in a dose which selectively blocks the 5-HT2A receptor.
  • The complaint notes that the use of the accused product would infringe one or more claims of the RE ’839 patent (Compl. ¶40).

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

  • Issued: May 1, 2018

The Invention Explained

  • Problem Addressed: The patent addresses the "residual phase" of schizophrenia, which is characterized by negative symptoms (e.g., emotional withdrawal, apathy) and general psychopathology that are often not well-treated by many antipsychotic drugs available on the market (U.S. Patent 10,960,009, col. 1:56-col. 2:2).
  • The Patented Solution: The invention provides a method for treating these specific residual symptoms. The method comprises administering an effective amount of a compound of Formula I to a patient after the patient has already been treated for the acute, or positive, symptoms of schizophrenia. The treatment's efficacy is measured by a significant improvement on the Prosocial PANSS Factor, a specific clinical metric for social functioning (’227 Patent, Abstract; Claim 1).
  • Technical Importance: This method provides a targeted therapy for a difficult-to-treat phase of schizophrenia, aiming to improve social function and quality of life after acute psychosis has subsided.

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶67).
  • Claim 1 requires:
    • A method for the treatment of residual symptoms of schizophrenia as defined in the Positive and Negative Syndrome Scale (PANSS),
    • comprising administering to a patient, after treatment of acute symptoms of schizophrenia,
    • an effective amount of a compound of Formula I (or its salt form),
    • wherein the patient significantly improves on the Prosocial PANSS Factor change from baseline.
  • The complaint notes that the use of the accused product would infringe one or more claims of the ’227 patent (Compl. ¶66).

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

  • Patent Identification: U.S. Patent No. 10,960,009, "Methods of Treating Schizophrenia and Depression," issued March 30, 2021.
  • Technology Synopsis: This patent claims a method for treating the negative symptoms of schizophrenia. The claimed method involves administering a specific daily dose (40 mg to 60 mg) of a particular Formula I compound (’009 Patent, Claim 1).
  • Asserted Claims: The complaint asserts independent claim 1 (Compl. ¶93).
  • Accused Features: The complaint alleges that Aurobindo's proposed product label will direct the administration of lumateperone for treating negative symptoms of schizophrenia in the claimed 40 mg to 60 mg daily dosage range (Compl. ¶94).

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

  • Patent Identification: U.S. Patent No. 11,026,951, "Methods of Treating Bipolar Disorder," issued June 8, 2021.
  • Technology Synopsis: This patent claims a method for treating bipolar I and/or bipolar II disorder. The claimed method specifies that the Formula I compound is used as a monotherapy, meaning it is not used in combination with another antipsychotic agent (’951 Patent, Claim 1).
  • Asserted Claims: The complaint asserts independent claim 1 (Compl. ¶119).
  • Accused Features: The complaint alleges that Aurobindo's proposed label will direct the use of its product for treating bipolar disorder as a monotherapy (Compl. ¶120).

U.S. Patent No. 10,695,345 - "Pharmaceutical Capsule Compositions Comprising Lumateperone Mono-Tosylate"

  • Patent Identification: U.S. Patent No. 10,695,345, "Pharmaceutical Capsule Compositions Comprising Lumateperone Mono-Tosylate," issued June 30, 2020.
  • Technology Synopsis: This patent claims a specific pharmaceutical capsule formulation. The claim recites a blend of lumateperone mono-tosylate in solid crystal form with five specific excipients (mannitol, croscarmellose sodium, talc, magnesium stearate) within defined weight percentage ranges, filled into a gelatin capsule (’345 Patent, Claim 1).
  • Asserted Claims: The complaint asserts independent claim 1 (Compl. ¶145).
  • Accused Features: The complaint alleges on information and belief that Aurobindo's ANDA Product is a pharmaceutical capsule comprising lumateperone mono-tosylate in a blend with the specific excipients in the specific amounts recited in claim 1 (Compl. ¶146).

U.S. Patent No. 11,690,842 - "Pharmaceutical Capsule Compositions Comprising Lumateperone Mono-Tosylate"

  • Patent Identification: U.S. Patent No. 11,690,842, "Pharmaceutical Capsule Compositions Comprising Lumateperone Mono-Tosylate," issued July 4, 2023.
  • Technology Synopsis: This patent claims a pharmaceutical capsule with the same blend of ingredients as the ’345 Patent but adds a functional requirement. The claim requires that a single capsule dissolve in a specific acidic solution to a certain extent after set time intervals (e.g., at least 85% after 15 minutes) (’842 Patent, Claim 1).
  • Asserted Claims: The complaint asserts independent claim 1 (Compl. ¶171).
  • Accused Features: The complaint alleges that Aurobindo's ANDA product contains the claimed excipients and possesses the specific dissolution profile recited in claim 1 (Compl. ¶172).

U.S. Patent No. 11,806,348 - "Methods of Treatment Using Pharmaceutical Capsule Compositions Comprising Lumateperone Mono-Tosylate"

  • Patent Identification: U.S. Patent No. 11,806,348, "Methods of Treatment Using Pharmaceutical Capsule Compositions Comprising Lumateperone Mono-Tosylate," issued November 7, 2023.
  • Technology Synopsis: This patent claims a method of treatment for disorders mediated by certain neurological pathways (5-HT2A receptor, SERT, and/or dopamine D1/D2 receptors). The method requires administering the specific capsule formulation from the ’345 and ’842 patents, wherein the capsule contains an amount of lumateperone mono-tosylate equivalent to a specific range of the free base form (0.01 to 30 mg or 35 to 45 mg) (’348 Patent, Claim 1).
  • Asserted Claims: The complaint asserts independent claim 1 (Compl. ¶197).
  • Accused Features: The complaint alleges that Aurobindo's proposed label will direct treatment using a capsule that contains the claimed formulation and dosage amount (Compl. ¶198).

U.S. Patent No. 11,753,419 - "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)-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"

  • Patent Identification: U.S. Patent No. 11,753,419, "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)-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," issued September 12, 2023.
  • Technology Synopsis: This patent claims a specific compound of Formula I, which appears to be a dimer of the active moiety in lumateperone, and its use in treating CNS and cardiac disorders (’419 Patent, Abstract).
  • Asserted Claims: The complaint asserts independent claim 1 (Compl. ¶223).
  • Accused Features: The complaint alleges that Aurobindo's ANDA product contains the claimed Formula I compound in free or pharmaceutically acceptable salt form (Compl. ¶224). This suggests an allegation that the accused product contains this compound, potentially as a manufacturing impurity or byproduct.

III. The Accused Instrumentality

Product Identification

  • Aurobindo's Abbreviated New Drug Application ("ANDA") No. 219085 product ("Aurobindo's ANDA Product") (Compl. ¶2). The product is a generic version of CAPLYTA® (lumateperone) capsules, 42 mg (Compl. ¶¶1, 25).

Functionality and Market Context

  • The accused product is a generic drug containing lumateperone that, upon FDA approval, would be marketed for the same indications as CAPLYTA®, which includes the treatment of schizophrenia and bipolar depression in adults (Compl. ¶¶24, 25). The complaint alleges that Aurobindo's submission of its ANDA to the FDA seeks approval to manufacture and sell this generic product prior to the expiration of the Patents-in-Suit (Compl. ¶2). This act of filing an ANDA with a Paragraph IV certification is the statutory basis for the infringement action under the Hatch-Waxman Act (Compl. ¶¶16, 26, 44).

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 use of Aurobindo's product as directed by its proposed label would involve treating one or more 5-HT2A-related disorders. ¶42 col. 9:41-42
comprising administering to a patient in need thereof a Compound of Formula I... in free or pharmaceutically acceptable salt form, Aurobindo’s ANDA Product contains lumateperone, which the complaint identifies as a Formula I compound, in a salt form. The complaint provides a diagram of Formula I (Compl. ¶41). ¶39, ¶42 col. 9:43-47
in a dose which selectively blocks the 5-HT2A receptor. The use of Aurobindo’s product as directed by its proposed label would involve administering a dose that selectively blocks the 5-HT2A receptor. ¶42 col. 9:46-47
  • Identified Points of Contention:
    • Scope Questions: A central question will be the construction of the term "selectively blocks the 5-HT2A receptor." Does "selectively" refer to selectivity over other receptors (e.g., dopamine D2 receptors), or does it imply a specific low-dose range where 5-HT2A antagonism is the primary effect, as suggested by the patent's specification?
    • Technical Questions: What evidence does the complaint provide that the 42 mg dose in Aurobindo's proposed label meets the functional requirement of "selectively" blocking the 5-HT2A receptor as defined by the patent?

U.S. Patent No. 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, The use of Aurobindo’s ANDA Product as directed by its proposed label would involve treating residual symptoms of schizophrenia. ¶68 col. 29:39-42
comprising administering to a patient in need thereof, after treatment of acute symptoms of schizophrenia with an antipsychotic agent, The proposed label would direct administration of the product after treatment of acute symptoms of schizophrenia. ¶68 col. 29:42-45
an effective amount of a compound of Formula I... in free or pharmaceutically acceptable salt form; The product contains an effective amount of lumateperone, which the complaint identifies as a Formula I compound, in a salt form. The complaint includes a diagram of Formula I (Compl. ¶67). ¶65, ¶68 col. 29:45-51
wherein the patient significantly improves on the Prosocial PANSS Factor change from baseline. The complaint alleges that use according to the proposed label would involve the complete method recited in claim 1, which includes this efficacy outcome. ¶68 col. 29:52-54
  • Identified Points of Contention:
    • Scope Questions: Will Aurobindo’s proposed label for general schizophrenia treatment be construed as actively encouraging, teaching, or promoting the specific patented method of treating residual symptoms after acute symptoms have been addressed? This raises a core question of induced infringement.
    • Technical Questions: Does the clinical data supporting Aurobindo's ANDA demonstrate bioequivalence in a manner that would necessarily lead to the claimed "significant improve[ment] on the Prosocial PANSS Factor" when used for residual symptoms?

V. Key Claim Terms for Construction

The Term: "selectively blocks the 5-HT2A receptor" (from RE ’839 Patent, Claim 1)

  • Context and Importance: This term is a functional limitation that defines the core mechanism of the claimed method. The scope of "selectively" is critical to determining infringement, as it distinguishes the claimed method from broader antipsychotic treatments that may affect multiple receptors. Practitioners may focus on this term because infringement will depend on whether Aurobindo's proposed 42 mg dose and its resulting receptor activity profile fall within the construed scope of this term.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim language itself does not specify a degree of selectivity or a dosage, which may support an argument that the term only requires the compound to have a blocking effect on the 5-HT2A receptor that is distinguishable from its other effects (RE ’839 Patent, col. 9:46-47).
    • Evidence for a Narrower Interpretation: The specification describes "differential dose-dependent effects, selectively targeting the 5-HT2A receptor at low doses, while progressively interacting with the D2 receptor at higher doses" (RE ’839 Patent, col. 2:61-65). This language may support a construction that limits "selectively" to a specific low-dose range where 5-HT2A antagonism occurs with minimal D2 receptor interaction.

The Term: "residual symptoms of schizophrenia" (from ’227 Patent, Claim 1)

  • Context and Importance: This term defines the specific condition being treated and distinguishes it from the "acute symptoms" of schizophrenia. The infringement analysis for this method claim will hinge on whether Aurobindo's product label induces physicians to treat this particular patient population. Practitioners may focus on this term because the case could turn on whether a general schizophrenia label is sufficient to induce infringement of a claim directed to a specific phase of the illness.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party might argue that "residual symptoms" are simply a subset of the overall symptoms of schizophrenia, and thus a general label for schizophrenia inherently covers their treatment. The claim itself references the PANSS, a scale used for general schizophrenia assessment (’227 Patent, col. 29:40-42).
    • Evidence for a Narrower Interpretation: The claim explicitly requires administration "after treatment of acute symptoms," creating a temporal and clinical distinction (’227 Patent, col. 29:43-45). The background of related patents describes residual symptoms as a distinct phase of the illness characterized by negative symptoms like emotional withdrawal, which are often "not well-treated by many antipsychotic drugs" (U.S. Patent 10,960,009, col. 1:56-64). This could support a narrow construction that clearly separates the claimed method from the treatment of acute psychosis.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges that Aurobindo will actively induce infringement of the asserted method claims. This allegation is based on the contents of Aurobindo's proposed product labeling, which will allegedly instruct physicians and patients to administer the generic product in a manner that performs the steps of the patented methods (Compl. ¶¶48, 74, 100, 126, 152, 178, 204, 230). The complaint further alleges contributory infringement, stating the ANDA product is not a staple article and is especially made or adapted for infringing use (Compl. ¶¶49, 75, 101, 127, 153, 179, 205, 231).

Willful Infringement

  • The complaint alleges that Aurobindo 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. ¶¶52, 78, 104, 130, 156, 182, 208, 234). This allegation is predicated on Aurobindo's knowledge of the patents, which are listed in the FDA's Orange Book, and its act of filing a Paragraph IV certification against them.

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

  • A core issue will be one of induced infringement: Can Plaintiff demonstrate that Aurobindo's proposed product label for general indications like schizophrenia and bipolar disorder will actively encourage or instruct medical professionals to perform the specific, narrower methods claimed in the patents, such as treating only "residual symptoms" after an acute phase, or using the drug as a monotherapy for bipolar disorder?
  • A key evidentiary question will be one of formulation identity: For the patents claiming specific capsule compositions and dissolution profiles, the dispute will center on whether Aurobindo's confidential ANDA formulation literally contains the claimed blend of excipients in the claimed weight percentages and exhibits the claimed functional dissolution characteristics.
  • A central question of claim construction will be the scope of functional language, particularly what it means for a dose to "selectively block the 5-HT2A receptor." The resolution of this issue will determine whether Aurobindo's 42 mg dosage strength falls within the scope of the method claimed in the RE '839 patent.