DCT

3:24-cv-04312

Intra Cellular Therapies Inc v. Alkem Laboratories Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:24-cv-04312, D.N.J., 03/28/2024
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant is a foreign corporation subject to personal jurisdiction in the district. The complaint alleges Defendant intends to market its generic product throughout the United States, including New Jersey, and derives substantial revenue from the state.
  • Core Dispute: Plaintiff alleges that Defendant's submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of Plaintiff's CAPLYTA® (lumateperone) drug product constitutes an act of infringement of nine U.S. patents.
  • Technical Context: The patents-in-suit relate to the antipsychotic compound lumateperone, including specific pharmaceutical compositions, methods of treating neuropsychiatric disorders such as schizophrenia and bipolar disorder, and a related chemical compound.
  • Key Procedural History: This is a Hatch-Waxman action filed under 35 U.S.C. § 271(e)(2), triggered by a Notice Letter from Defendant dated February 16, 2024, informing Plaintiff of its ANDA submission. The complaint states Defendant filed Paragraph IV certifications for seven of the nine asserted patents, alleging they are invalid, unenforceable, and/or not infringed by its proposed generic product.

Case Timeline

Date Event
2008-05-27 RE ’839 Patent Priority Date
2013-12-03 ’227, ’009, ’951 Patent Priority Date
2018-05-01 U.S. Patent No. 9,956,227 Issues
2018-08-31 ’345, ’084, ’842, ’348 Patent Priority Date
2019-12-11 ’419 Patent Priority Date
2020-06-30 U.S. Patent No. 10,695,345 Issues
2021-03-30 U.S. Patent No. 10,960,009 Issues
2021-06-08 U.S. Patent No. 11,026,951 Issues
2021-07-06 U.S. Patent No. 11,052,084 Issues
2021-12-07 U.S. Reissue Patent No. RE48,839 Issues
2023-07-04 U.S. Patent No. 11,690,842 Issues
2023-09-12 U.S. Patent No. 11,753,419 Issues
2023-11-07 U.S. Patent No. 11,806,348 Issues
2024-02-16 Defendant Alkem sends ANDA Notice Letter to Plaintiff
2024-03-28 Complaint Filing Date

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

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

  • Patent Identification: U.S. Reissue Patent No. RE48,839, "Methods and Compositions for Sleep Disorders and Other Disorders," issued December 7, 2021 (Compl. ¶33).

The Invention Explained

  • Problem Addressed: The patent addresses the need for treatments for various central nervous system disorders associated with 5-HT2A receptor modulation, such as anxiety, depression, psychosis, and sleep disorders (RE48,839 Patent, col. 3:32-41).
  • The Patented Solution: The invention claims a method of treating these disorders by administering a specific class of compounds, including lumateperone (identified as Formula I), which acts as a 5-HT2A receptor antagonist (RE48,839 Patent, col. 3:28-34). Asserted claim 1 specifically recites administering the compound "in a dose which selectively blocks the 5-HT2A receptor" (Compl. ¶41).
  • Technical Importance: The technology provides a therapeutic approach that targets a key serotonin receptor pathway implicated in a wide range of neuropsychiatric conditions (RE48,839 Patent, col. 3:28-34).

Key Claims at a Glance

  • The complaint asserts "one or more claims" and identifies independent claim 1 as an example (Compl. ¶40-41).
  • Essential elements of Claim 1:
    • A method for the treatment of one or more 5-HT2A-related disorders.
    • Comprising administering to a patient a Compound of Formula I.
    • In a free or pharmaceutically acceptable salt form.
    • In a dose which selectively blocks the 5-HT2A receptor.

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

  • Patent Identification: U.S. Patent No. 9,956,227, "Method for the Treatment of Residual Symptoms of Schizophrenia," issued May 1, 2018 (Compl. ¶59).

The Invention Explained

  • Problem Addressed: The patent addresses the unmet need for treating the residual symptoms of schizophrenia, such as negative symptoms (e.g., social withdrawal) and cognitive impairment, which often persist after the acute, positive symptoms (e.g., hallucinations) have been managed ('227 Patent, col. 1:44-67).
  • The Patented Solution: The invention is a method for treating these residual symptoms. The method involves administering lumateperone (Formula I) to a patient after their acute symptoms have already been treated with an antipsychotic agent. The method is further defined by the outcome, requiring that the patient "significantly improves on the Prosocial PANSS Factor change from baseline" ('227 Patent, col. 43:10-14).
  • Technical Importance: This technology targets a specific and challenging phase of schizophrenia management, aiming to improve social function and quality of life when patients are not in an acute psychotic state ('227 Patent, col. 2:1-3).

Key Claims at a Glance

  • The complaint asserts "one or more claims" and identifies independent claim 1 as an example (Compl. ¶65-66).
  • Essential elements of Claim 1:
    • 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 with an antipsychotic agent, an effective amount of a compound of Formula I.
    • In free or pharmaceutically acceptable salt form.
    • Wherein the patient significantly improves on the Prosocial PANSS Factor change from baseline.

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 (Compl. ¶84).
  • Technology Synopsis: The patent claims a method for treating the negative symptoms of schizophrenia by administering a specific daily dose of lumateperone (40 mg to 60 mg per day) ('009 Patent, col. 39:11-28). This differs from broader treatment claims by focusing on a specific symptom cluster and dosage range.
  • Asserted Claims: Independent claim 1 is asserted as an example (Compl. ¶91).
  • Accused Features: The use of Alkem's ANDA Product, as directed by its proposed label, to treat negative symptoms of schizophrenia by administering a daily dose of 40 mg to 60 mg (Compl. ¶92).

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 (Compl. ¶109).
  • Technology Synopsis: The patent claims a method for treating bipolar disorder I and/or bipolar II. The method specifies that the claimed compound (lumateperone) is administered as a monotherapy, i.e., "not used in combination with another antipsychotic agent" ('951 Patent, col. 39:9-24).
  • Asserted Claims: Independent claim 1 is asserted as an example (Compl. ¶117).
  • Accused Features: The use of Alkem's ANDA Product, as directed by its proposed label, to treat bipolar disorder without a concomitant antipsychotic agent (Compl. ¶118).

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 (Compl. ¶135).
  • Technology Synopsis: This patent claims a specific pharmaceutical composition. It covers a capsule for oral administration containing lumateperone mono-tosylate in a solid crystal form, blended with a specific set of excipients (mannitol, croscarmellose sodium, talc, magnesium stearate) within defined weight-percentage ranges ('345 Patent, col. 19:40-62).
  • Asserted Claims: Independent claim 1 is asserted as an example (Compl. ¶143).
  • Accused Features: Alkem's ANDA Product itself is accused of infringing, as it is alleged to be a pharmaceutical capsule comprising lumateperone mono-tosylate with the claimed excipients in the claimed amounts (Compl. ¶144).

U.S. Patent No. 11,052,084 - "Pharmaceutical Capsule Compositions Comprising Lumateperone Mono-Tosylate"

  • Patent Identification: U.S. Patent No. 11,052,084, "Pharmaceutical Capsule Compositions Comprising Lumateperone Mono-Tosylate," issued July 6, 2021 (Compl. ¶161).
  • Technology Synopsis: This patent is similar to the '345 Patent but adds a dosage limitation to the composition claim. It covers a capsule with the same specified excipients but further requires that the capsule comprise lumateperone mono-tosylate in an amount equivalent to 0.01 to 30 mg of lumateperone free base ('084 Patent, col. 19:39-65).
  • Asserted Claims: Independent claim 1 is asserted as an example (Compl. ¶169).
  • Accused Features: Alkem's 10.5 mg and 21 mg ANDA Products are accused of infringing, as they are alleged to contain the claimed composition within the specified dosage range (Compl. ¶170).

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 (Compl. ¶187).
  • Technology Synopsis: This patent builds on the composition claims of prior patents by adding a functional, performance-based limitation. It claims a capsule with the specified excipients that also meets a specific dissolution profile (e.g., dissolving to at least 85% after 15 minutes in a specific acidic solution) ('842 Patent, col. 19:34-20:5).
  • Asserted Claims: Independent claim 1 is asserted as an example (Compl. ¶195).
  • Accused Features: Alkem's ANDA Product is accused of infringing by both containing the claimed composition and possessing the claimed dissolution profile (Compl. ¶196).

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 (Compl. ¶213).
  • Technology Synopsis: This patent claims a method of treatment using the specific compositions claimed in sister patents. It covers a method for treating diseases mediated by the 5-HT2A receptor, SERT, and/or dopamine pathways by administering a pharmaceutical capsule comprising lumateperone mono-tosylate within specific dosage ranges (0.01 to 30 mg or 35 to 45 mg) and with the specified excipients ('348 Patent, col. 19:24-42).
  • Asserted Claims: Independent claim 1 is asserted as an example (Compl. ¶221).
  • Accused Features: The use of Alkem's ANDA Product is accused of infringing by treating the specified disorders through administration of a capsule with the claimed composition and dosage amounts (Compl. ¶222).

U.S. Patent No. 11,753,419 - "entitled with a detailed chemical name for a lumateperone dimer"

  • Patent Identification: U.S. Patent No. 11,753,419, entitled with a detailed chemical name for a lumateperone dimer, issued September 12, 2023 (Compl. ¶239).
  • Technology Synopsis: This patent claims a specific chemical compound, which appears to be a dimer of the active ingredient lumateperone ('419 Patent, claim 1). Such compounds may be present in a drug product as a manufacturing by-product or impurity.
  • Asserted Claims: Independent claim 1 is asserted as an example (Compl. ¶247).
  • Accused Features: Alkem's ANDA Product itself is accused of infringing by allegedly containing the claimed dimer compound (Compl. ¶248).

III. The Accused Instrumentality

Product Identification

Defendant's proposed generic lumateperone capsules in 10.5 mg, 21 mg, and 42 mg strengths, for which it submitted ANDA No. 219200 to the FDA ("Alkem's ANDA Product") (Compl. ¶2).

Functionality and Market Context

The accused product is a generic version of Plaintiff's CAPLYTA®, an approved treatment for schizophrenia and depressive episodes associated with bipolar I or II disorder (Compl. ¶23-24). The complaint alleges that upon approval, Alkem will manufacture and sell its ANDA Product for the same indications, in direct competition with Plaintiff's branded product (Compl. ¶6, ¶13). The complaint includes a chemical structure diagram depicting lumateperone, the active ingredient in the accused product (Compl. p. 9).

IV. Analysis of Infringement Allegations

RE48,839 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 use of Alkem's ANDA Product as directed by its proposed label would involve treating one or more 5-HT2A-related disorders. ¶42 col. 3:32-41
comprising administering to a patient in need thereof a Compound of Formula I... Alkem's ANDA Product contains lumateperone, which is a compound of Formula I. A visual in the complaint depicts this chemical structure. ¶39, ¶42; p. 9 col. 2:5-15
in free or pharmaceutically acceptable salt form, The lumateperone in Alkem's ANDA Product is in a free or pharmaceutically acceptable salt form. ¶42 col. 3:55-56
in a dose which selectively blocks the 5-HT2A receptor. The use of Alkem's ANDA Product as directed by its proposed label would involve administering a dose that selectively blocks the 5-HT2A receptor. ¶42 col. 2:1-3
  • Identified Points of Contention:
    • Scope Questions: The infringement analysis for this method claim will depend on the specific indications for use included in Defendant's proposed product labeling. A central question will be whether the label's directed uses fall within the scope of "5-HT2A-related disorders" as understood in the patent.
    • Technical Questions: A key technical question may be whether the doses specified in Defendant's proposed label in fact "selectively block" the 5-HT2A receptor. This functional language may require expert testimony to determine if the alleged infringing use meets this limitation, both literally and under the doctrine of equivalents.

'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 as defined in the Positive and Negative Syndrome Scale (PANSS) for Schizophrenia, The use of Alkem's ANDA Product as directed by its proposed label would involve treating residual symptoms of schizophrenia. ¶67 col. 2:32-34
comprising administering to a patient in need thereof, after treatment of acute symptoms of schizophrenia with an antipsychotic agent, The use of Alkem's ANDA Product as directed by its proposed label would involve administration after prior treatment with an antipsychotic agent. ¶67 col. 1:21-25
an effective amount of a compound of Formula I... Alkem's ANDA Product contains lumateperone, the compound of Formula I depicted in the complaint's visual. ¶64, ¶67; p. 13 col. 11:11-23
in free or pharmaceutically acceptable salt form; The lumateperone in Alkem's ANDA Product is in a free or pharmaceutically acceptable salt form. ¶67 col. 11:24-25
wherein the patient significantly improves on the Prosocial PANSS Factor change from baseline. The use of Alkem's ANDA Product as directed by its proposed label would result in the patient's significant improvement on the Prosocial PANSS Factor. ¶67 col. 14:1-14
  • Identified Points of Contention:
    • Scope Questions: A primary dispute may arise over the claim requirement for administration "after treatment of acute symptoms... with an antipsychotic agent." The infringement analysis will turn on whether Defendant's proposed label instructs or encourages this specific sequence of treatment, or if it is directed at a broader patient population.
    • Technical Questions: The "wherein the patient significantly improves" clause presents a significant point of contention. The parties may dispute whether this is a required element of the infringing method that Plaintiff must prove, or merely a statement of the intended result of practicing the method.

V. Key Claim Terms for Construction

  • RE '839 Patent, Claim 1

    • The Term: "selectively blocks the 5-HT2A receptor"
    • Context and Importance: This functional language is central to defining the claimed method. Practitioners may focus on this term because infringement requires not just administering the compound, but doing so in a way that achieves a specific pharmacological effect relative to other receptors. The definition will determine the scope of evidence needed to prove infringement.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification describes lumateperone as having "high selectivity for the serotonin transporter (SERT) relative to the heterocycle fused gamma-carboline containing 4-fluorophenylbutanone," which suggests selectivity is a relative concept (RE48,839 Patent, col. 3:62-67).
      • Evidence for a Narrower Interpretation: The specification also states the compound "selectively target[s] the 5-HT2A receptor at low doses, while progressively interacting with the D2 receptor at higher doses," which could be used to argue that "selectively" requires a dose low enough to avoid significant D2 receptor interaction (RE48,839 Patent, col. 4:63-67).

  • '227 Patent, Claim 1

    • The Term: "wherein the patient significantly improves on the Prosocial PANSS Factor change from baseline"
    • Context and Importance: The construction of this "wherein" clause is critical. If it is interpreted as a necessary limitation of the claim, Plaintiff would need to prove that the directed use of the generic product necessarily results in this specific clinical outcome. If it is interpreted as merely stating an intended purpose or result, infringement would be met by performing the preceding administration steps for that purpose.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation (Not a Limitation): Parties arguing this is not a separate limitation may point out that it describes the result of the preceding active steps, rather than an action taken by the administrator of the method.
      • Evidence for a Narrower Interpretation (Is a Limitation): The patent's prosecution history (not provided in the complaint) may be relevant. The specification also includes clinical data showing this specific outcome, which may be argued to define the scope of the invention (e.g., '227 Patent, Fig. 4).

VI. Other Allegations

  • Indirect Infringement: For all asserted method patents, the complaint alleges active inducement of infringement on the basis that Defendant's proposed product labeling will instruct physicians and patients to perform the patented methods (Compl. ¶48, ¶73, ¶98, ¶124, ¶228). For all patents, the complaint alleges contributory infringement on the basis that Defendant's ANDA Product is not a staple article of commerce and is especially made or adapted for infringing uses (Compl. ¶49, ¶74, ¶99, ¶125, ¶151, ¶177, ¶203, ¶229, ¶255).
  • Willful Infringement: The complaint alleges that Defendant 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, ¶77, ¶102, ¶128, ¶154, ¶180, ¶206, ¶232, ¶258). This allegation is based on Defendant's knowledge of the patents as evidenced by its ANDA submission and the February 16, 2024 Notice Letter.

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

  • A key evidentiary question will be one of compositional identity: does Alkem's ANDA Product contain the exact blend of excipients, in the specific weight percentages, exhibit the claimed dissolution profile, and contain the specific dimer compound as required by the various composition and compound patents ('345, '084, '842, '419)?
  • A central legal issue will be one of infringement by labeling: will Alkem's final, FDA-approved label instruct physicians and patients to perform the specific methods claimed, such as treating "residual symptoms" after other therapies ('227 Patent), treating "negative symptoms" at a specific 40-60 mg/day dose ('009 Patent), or treating bipolar disorder as a monotherapy ('951 Patent)?
  • A crucial issue will be one of claim construction: can functional "wherein" clauses, such as "wherein the patient significantly improves on the Prosocial PANSS Factor" ('227 Patent), be interpreted as affirmative limitations of the claimed method that Plaintiff must prove are met by the accused conduct, or are they merely statements of intended result?