DCT

3:24-cv-04325

Intra Cellular Therapies Inc v. MSN Laboratories Private Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:24-cv-04325, D.N.J., 03/28/2024
  • Venue Allegations: Venue is alleged to be proper because Defendant is a foreign corporation, making it subject to suit in any judicial district where it is subject to personal jurisdiction.
  • Core Dispute: Plaintiff alleges that Defendant's Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's CAPLYTA® (lumateperone) capsules constitutes an act of infringement of nine U.S. patents covering the lumateperone compound, specific pharmaceutical formulations, and methods of use for treating certain central nervous system disorders.
  • Technical Context: The technology relates to pharmaceutical treatments for schizophrenia and bipolar depression, a significant market in neuropsychiatric medicine.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiff's receipt of a Paragraph IV Notice Letter from Defendant, which asserted that the patents-in-suit are invalid, unenforceable, or will not be infringed by Defendant's proposed generic product. Plaintiff has filed similar lawsuits against other generic drug manufacturers regarding the same product and patents.

Case Timeline

Date Event
2008-05-27 Priority Date for RE48,839 Patent
2013-12-03 Priority Date for U.S. Patent Nos. 9,956,227; 10,960,009; 11,026,951
2018-05-01 Issue Date for U.S. Patent No. 9,956,227
2018-08-31 Priority Date for U.S. Patent Nos. 10,695,345; 11,052,084; 11,690,842; 11,806,348
2019-12-11 Priority Date for U.S. Patent No. 11,753,419
2020-06-30 Issue Date for U.S. Patent No. 10,695,345
2021-03-30 Issue Date for U.S. Patent No. 10,960,009
2021-06-08 Issue Date for U.S. Patent No. 11,026,951
2021-07-06 Issue Date for U.S. Patent No. 11,052,084
2021-12-07 Issue Date for U.S. Reissue Patent No. RE48,839
2023-07-04 Issue Date for U.S. Patent No. 11,690,842
2023-09-12 Issue Date for U.S. Patent No. 11,753,419
2023-11-07 Issue Date for U.S. Patent No. 11,806,348
2024-02-16 MSN's Notice Letter sent to Plaintiff
2024-03-28 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. (Compl. ¶32).

The Invention Explained

  • Problem Addressed: The patent’s background describes a need for treatments for central nervous system disorders associated with 5-HT2A receptor modulation, such as anxiety, depression, psychosis, schizophrenia, and sleep disorders. (U.S. Pat. No. 8,598,119, col. 1:31-41).
  • The Patented Solution: The invention claims a method for treating these disorders by administering a specific class of compounds, represented by Formula I, which are characterized as having serotonin 5-HT2A receptor antagonist activity. (Compl. ¶40; U.S. Pat. No. 8,598,119, Abstract). The patent asserts that these compounds display dose-dependent effects, selectively targeting the 5-HT2A receptor at lower doses, which makes them useful for treating conditions like sleep disorders and agitation. (U.S. Pat. No. 8,598,119, col. 3:63-67). The complaint provides a chemical structure diagram of Formula I. (Compl. ¶40, p. 9).
  • Technical Importance: The invention provided a therapeutic approach for CNS disorders by targeting the 5-HT2A receptor, aiming to achieve therapeutic benefits for a range of conditions including psychosis and sleep disorders. (U.S. Pat. No. 8,598,119, col. 1:31-41).

Key Claims at a Glance

  • The complaint asserts independent claim 1. (Compl. ¶40).
  • Essential elements of claim 1 include:
    • 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,
    • wherein the compound has a specified chemical structure (wherein X is O, —NH or —N(CH3); and Y is —O— or —C(O)—), in 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 RE ’839 patent, which may include dependent claims. (Compl. ¶39).

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. (Compl. ¶58).

The Invention Explained

  • Problem Addressed: The patent’s background section explains that while many antipsychotic drugs can treat the "active" or "acute" phase symptoms of schizophrenia (e.g., delusions, hallucinations), the "residual" phase symptoms (e.g., emotional withdrawal, social avoidance) are often not well-treated by available medications. (U.S. Pat. No. 9,956,227, col. 2:58-64).
  • The Patented Solution: The invention is a method for treating these specific residual symptoms of schizophrenia. The method requires administering a compound of Formula I to a patient after the patient's acute symptoms have been treated with an antipsychotic agent. A key aspect of the claimed method is that it is directed to a patient population that "significantly improves on the Prosocial PANSS Factor change from baseline," a specific clinical measure of social function. (Compl. ¶66; U.S. Pat. No. 9,956,227, col. 18:40-47). The complaint includes a visual of the claimed Formula I chemical structure. (Compl. ¶66, p. 13).
  • Technical Importance: This invention provided a targeted therapeutic strategy for a difficult-to-treat aspect of schizophrenia, aiming to improve social functioning in patients after an acute psychotic episode has subsided. (U.S. Pat. No. 9,956,227, col. 18:8-14).

Key Claims at a Glance

  • The complaint asserts independent claim 1. (Compl. ¶66).
  • Essential elements of claim 1 include:
    • A method for the treatment of residual symptoms of schizophrenia as defined in the Positive and Negative Syndrome Scale (PANSS) for Schizophrenia,
    • comprising administering to a patient in need thereof, after treatment of acute symptoms of schizophrenia with an antipsychotic agent,
    • an effective amount of a compound of Formula I with a specified 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 ’227 patent, which may include dependent claims. (Compl. ¶65).

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. ¶84).
  • Technology Synopsis: This patent claims a method for treating the negative symptoms of schizophrenia. The method involves administering a specific daily dosage range (40 mg to 60 mg) of the Formula I compound lumateperone. (Compl. ¶92; U.S. Pat. No. 10,960,009, col. 1:45-56).
  • Asserted Claims: The complaint asserts independent claim 1. (Compl. ¶92).
  • Accused Features: The complaint alleges that the use of MSN’s ANDA Product as directed by its proposed label will involve administering 40 mg to 60 mg of the claimed compound per day to treat negative symptoms of schizophrenia. (Compl. ¶93).

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. ¶110).
  • Technology Synopsis: The patent claims a method for treating bipolar I and/or bipolar II disorder. The method comprises administering the Formula I compound lumateperone as a monotherapy, meaning it is not used in combination with another antipsychotic agent. (Compl. ¶118; U.S. Pat. No. 11,026,951, col. 1:45-53).
  • Asserted Claims: The complaint asserts independent claim 1. (Compl. ¶118).
  • Accused Features: It is alleged that MSN's proposed label will direct the use of its product to treat bipolar disorder without combination with another antipsychotic agent. (Compl. ¶119).

Multi-Patent Capsule: U.S. Patent No. 10,695,345

  • Patent Identification: 10,695,345, “Pharmaceutical Capsule Compositions Comprising Lumateperone Mono-Tosylate,” issued June 30, 2020. (Compl. ¶136).
  • Technology Synopsis: This patent claims a specific pharmaceutical capsule formulation. The claims recite lumateperone mono-tosylate in solid crystal form, blended with specific excipients (mannitol, croscarmellose sodium, talc, and magnesium stearate) within defined weight percentage ranges, filled into a gelatin capsule. (Compl. ¶144; U.S. Pat. No. 10,695,345, col. 4:56-65).
  • Asserted Claims: The complaint asserts independent claim 1. (Compl. ¶144).
  • Accused Features: The complaint alleges that MSN’s ANDA Product is a pharmaceutical capsule comprising lumateperone mono-tosylate in solid crystal form with the specific excipients in the claimed amounts. (Compl. ¶145).

Multi-Patent Capsule: U.S. Patent No. 11,052,084

  • Patent Identification: 11,052,084, “Pharmaceutical Capsule Compositions Comprising Lumateperone Mono-Tosylate,” issued July 6, 2021. (Compl. ¶162).
  • Technology Synopsis: This patent claims a pharmaceutical capsule formulation similar to the ’345 Patent. It adds a limitation specifying that the capsule comprises an amount of lumateperone mono-tosylate equivalent to 0.01 to 30 mg of lumateperone free base. (Compl. ¶170; U.S. Pat. No. 11,052,084, col. 20:1-3).
  • Asserted Claims: The complaint asserts independent claim 1. (Compl. ¶170).
  • Accused Features: The complaint alleges MSN's ANDA Product is a capsule comprising the claimed components and dosage amount. (Compl. ¶171).

Multi-Patent Capsule: U.S. Patent No. 11,690,842

  • Patent Identification: 11,690,842, “Pharmaceutical Capsule Compositions Comprising Lumateperone Mono-Tosylate,” issued July 4, 2023. (Compl. ¶188).
  • Technology Synopsis: This patent claims a pharmaceutical capsule formulation similar to the ’345 and ’084 Patents. It adds a functional limitation requiring the capsule to meet a specific dissolution profile in hydrochloric acid over time (e.g., at least 85% dissolved after 15 minutes). (Compl. ¶196; U.S. Pat. No. 11,690,842, col. 20:8-13).
  • Asserted Claims: The complaint asserts independent claim 1. (Compl. ¶196).
  • Accused Features: The complaint alleges MSN's ANDA Product comprises the claimed excipients and possesses the specific dissolution profile. (Compl. ¶197).

Multi-Patent Capsule: U.S. Patent No. 11,806,348

  • Patent Identification: 11,806,348, “Methods of Treatment Using Pharmaceutical Capsule Compositions Comprising Lumateperone Mono-Tosylate,” issued November 7, 2023. (Compl. ¶214).
  • Technology Synopsis: This patent claims a method of treating disorders mediated by specific neurological pathways (5-HT2A receptor, SERT, and/or dopamine D1/D2 receptors). The method requires administering the specific pharmaceutical capsule formulation claimed in related patents. (Compl. ¶222; U.S. Pat. No. 11,806,348, col. 19:35-46).
  • Asserted Claims: The complaint asserts independent claim 1. (Compl. ¶222).
  • Accused Features: The complaint alleges that the proposed label for MSN's ANDA Product will direct administration of the capsule to treat disorders mediated by the claimed pathways. (Compl. ¶223).

Multi-Patent Capsule: U.S. Patent No. 11,753,419

  • Patent Identification: 11,753,419, entitled with a long chemical name for treating CNS and cardiac disorders, issued September 12, 2023. (Compl. ¶240).
  • Technology Synopsis: This patent claims a specific chemical compound of Formula I, which appears to be a dimer or related substance of lumateperone, either in free base or salt form. (Compl. ¶248; U.S. Pat. No. 11,753,419, Abstract).
  • Asserted Claims: The complaint asserts independent claim 1. (Compl. ¶248).
  • Accused Features: The complaint alleges upon information and belief that MSN's ANDA Product contains the claimed Formula I compound. (Compl. ¶249).

III. The Accused Instrumentality

  • Product Identification: Defendant MSN's ANDA Product, identified as a generic version of CAPLYTA® (lumateperone) capsules in 10.5 mg, 21 mg, and 42 mg dosage strengths, submitted to the FDA under ANDA No. 219248. (Compl. ¶¶ 1, 2).
  • Functionality and Market Context: The accused product contains the active pharmaceutical ingredient lumateperone and is intended for the treatment of schizophrenia and depressive episodes associated with bipolar I or II disorder. (Compl. ¶¶ 23, 24, 38, 64). The complaint alleges that upon FDA approval, MSN will market and sell its ANDA Product in the United States as a generic alternative to Plaintiff's branded CAPLYTA® product. (Compl. ¶13).

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 labeling for MSN's ANDA Product will allegedly direct its use for treating schizophrenia and bipolar disorder, which are alleged to be 5-HT2A-related disorders. ¶41 col. 1:33-38
comprising administering to a patient in need thereof a Compound of Formula I...in free or pharmaceutically acceptable salt form, MSN's ANDA Product contains lumateperone, which the complaint alleges is a compound of Formula I, in a free or pharmaceutically acceptable salt form. ¶38, ¶41 col. 2:5-18
in a dose which selectively blocks the 5-HT2A receptor. The proposed labeling will allegedly direct administration of a dose that selectively blocks the 5-HT2A receptor. ¶41 col. 3:63-67
  • Identified Points of Contention:
    • Scope Questions: A central question may be the construction of the term "selectively blocks the 5-HT2A receptor." Given that lumateperone is known to have activity at other receptors (e.g., dopamine D2, SERT), the defendant may argue its product does not "selectively" block only the 5-HT2A receptor. The patent’s disclosure of dose-dependent effects may be critical to resolving this scope question. (U.S. Pat. No. 8,598,119, col. 3:63-67).

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 proposed labeling for MSN's ANDA Product allegedly directs its use for treating schizophrenia, which would involve treating patients with residual symptoms. ¶67 col. 2:58-64
comprising administering to a patient in need thereof, after treatment of acute symptoms of schizophrenia with an antipsychotic agent, an effective amount of a compound of Formula I... The product labeling allegedly directs administration of lumateperone, a claimed Formula I compound, after a patient has been treated for acute symptoms with another antipsychotic. ¶67 col. 4:12-16
wherein the patient significantly improves on the Prosocial PANSS Factor change from baseline. The complaint alleges that the proposed label will direct a use that would involve treating patients who experience this clinical outcome. ¶67 col. 18:40-47
  • Identified Points of Contention:
    • Technical/Legal Questions: The "wherein the patient significantly improves" clause recites a clinical outcome. A key legal question will be whether infringement of this method claim can be induced by a product label, as the defendant does not directly control the patient's physiological response. This raises potential arguments regarding both infringement and the validity of claiming a patient's reaction to treatment.

V. Key Claim Terms for Construction

  • The Term: "selectively blocks the 5-HT2A receptor" (from RE '839 patent, claim 1)

  • Context and Importance: Practitioners may focus on this term because the mechanism of action of lumateperone involves multiple receptor pathways, not just 5-HT2A. The definition of "selectively" will be critical to determining whether the administration of a multi-receptor antagonist like lumateperone falls within the claim scope.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent specification describes the compound as having dose-dependent effects, noting it "selectively target[s] the 5-HT2A receptor at low doses, while progressively interacting with the D2 receptor at higher doses." (U.S. Pat. No. 8,598,119, col. 3:63-67). This could support an interpretation where "selectively" does not mean exclusively, but rather refers to the primary mode of action at a given dose.
    • Evidence for a Narrower Interpretation: A defendant could argue that the plain meaning of "selectively" requires a high degree of preference for the 5-HT2A receptor over all other receptors, such as D2 and SERT, where lumateperone also has known activity. (U.S. Pat. No. 8,598,119, col. 3:16-24).

  • The Term: "wherein the patient significantly improves on the Prosocial PANSS Factor change from baseline" (from '227 patent, claim 1)

  • Context and Importance: This term's construction is central because it defines the patient population and treatment outcome. Infringement hinges on whether MSN's product label instructs or encourages administration to patients for whom this outcome is an intended result.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent specification includes clinical trial data and figures illustrating this specific improvement, suggesting the inventors viewed this as a key, identifiable feature of their method. (U.S. Pat. No. 9,956,227, Fig. 4). A plaintiff may argue this establishes the objective basis for the claim and that a label directing treatment for symptoms measured by the PANSS scale necessarily induces infringement.
    • Evidence for a Narrower Interpretation: A defendant may argue that this is an indefinite and subjective standard that depends on the physician's and patient's individual assessment, making it impossible to determine infringement. The patent does not appear to provide a specific numerical threshold for what constitutes a "significant" improvement in the claim language itself, which could be a focus of an indefiniteness challenge.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement of infringement, stating that MSN plans to and will actively encourage infringement through its proposed product labeling, which will instruct medical professionals and patients to use the ANDA Product in a manner that directly infringes the method claims. (Compl. ¶¶ 47, 73, 99, 125, 151, 177, 203, 229, 255). The complaint also alleges contributory infringement on the basis that MSN's product and labeling are especially made for an infringing use and are not suitable for substantial non-infringing use. (Compl. ¶¶ 48, 74, 100, 126, 152, 178, 204, 230, 256).
  • Willful Infringement: Willfulness is alleged based on MSN having full knowledge of the patents-in-suit, including through their listing in the FDA's Orange Book and through MSN's own Paragraph IV notice letter, and proceeding with its ANDA submission without a reasonable basis for believing it would not be liable for infringement. (Compl. ¶¶ 51, 77, 103, 129, 155, 181, 207, 233, 259).

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

  • A core issue will be one of claim scope for method claims: Can the term "selectively blocks," in the context of a drug known to have multi-receptor activity, be construed to read on the administration of lumateperone? Furthermore, how will the court treat the patient-outcome limitation ("wherein the patient significantly improves"), a recurring and contentious issue in pharmaceutical patent litigation?
  • A key evidentiary question will be one of factual correspondence: For the numerous composition patents, the dispute will likely center on detailed analytical evidence. What does testing of MSN’s ANDA product reveal about its precise blend of excipients, dosage amounts, and dissolution profiles, and do these characteristics fall within the patented ranges?
  • A third determinative question will concern the ’419 patent: Does MSN's product contain the specific dimeric compound claimed in the '419 patent? This will likely involve sophisticated chemical analysis to determine not only the presence but also the quantity of the substance, raising questions about whether trace amounts of an impurity can constitute infringement.