DCT

3:24-cv-10234

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-10234, D.N.J., 11/01/2024
  • Venue Allegations: Venue is asserted on the basis that Defendant is a foreign corporation and subject to personal jurisdiction within the district.
  • Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (“ANDA”) seeking approval for a generic version of Plaintiff’s CAPLYTA® (lumateperone) drug product infringes three U.S. patents related to treatment methods and pharmaceutical compositions.
  • Technical Context: The technology concerns lumateperone, an atypical antipsychotic drug, and specific methods of its use for treating bipolar disorder, as well as particular pharmaceutical compositions containing the active ingredient.
  • Key Procedural History: This action arises under the Hatch-Waxman Act following Defendant’s submission of an ANDA with a Paragraph IV certification. The complaint notes this is the latest in a series of lawsuits filed by Plaintiff against Defendant concerning other patents related to the same CAPLYTA® drug product, with the prior cases having been consolidated.

Case Timeline

Date Event
2018-08-31 '043 Patent Priority Date
2019-07-07 '155 Patent Priority Date
2019-12-11 '792 Patent Priority Date
2024-02-16 Alkem's First Notice Letter to Plaintiff
2024-03-28 Plaintiff files first related lawsuit against Alkem
2024-08-02 Alkem's Second Notice Letter to Plaintiff
2024-08-29 Plaintiff files second related lawsuit against Alkem
2024-09-17 '155 Patent Issue Date
2024-10-22 '792 Patent Issue Date
2024-10-29 '043 Patent Issue Date
2024-11-01 Complaint Filing Date

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

U.S. Patent No. 12,090,155 - “Methods”

  • Patent Identification: U.S. Patent No. 12,090,155, “Methods,” issued September 17, 2024 (’155 Patent).
  • The Invention Explained:
    • Problem Addressed: The patent’s background section describes the challenges in treating bipolar disorder, noting that while many antipsychotics are approved for mania in Bipolar I Disorder, few are approved for Bipolar II Disorder, and existing options can cause significant side effects like sedation, metabolic issues, or suicidal thoughts (’155 Patent, col. 3:9-30). This creates a need for safer and more effective therapies specifically for Bipolar II Disorder (’155 Patent, col. 3:26-30).
    • The Patented Solution: The invention provides a method for treating Bipolar II Disorder by administering lumateperone. The detailed description highlights clinical trial data suggesting that lumateperone effectively treats depressive episodes in patients with Bipolar II disorder without triggering mania or causing common antipsychotic side effects such as akathisia or significant weight gain (’155 Patent, col. 5:7-29).
    • Technical Importance: The patented method claims a targeted therapeutic approach for Bipolar II Disorder, an indication with unmet medical needs, using a compound that may offer a more favorable safety profile than existing treatments (’155 Patent, col. 3:35-46).
  • Key Claims at a Glance:
    • The complaint asserts independent claims 1 and 22 (Compl. ¶39-40).
    • Claim 1 includes the following essential elements:
      • A method for treating a major depressive episode associated with Bipolar II Disorder.
      • The method comprises administering a therapeutically effective amount of lumateperone in mono-tosylate salt form.
      • Administration is once daily via a tablet or capsule.
      • The tablet or capsule comprises about 60 mg of lumateperone mono-tosylate with a pharmaceutically acceptable diluent or carrier.
    • Claim 22 includes the following essential elements:
      • A method for treating a depressive episode associated with Bipolar II Disorder.
      • The method comprises administering a therapeutically effective amount of lumateperone in mono-tosylate salt form.
      • Administration is once daily via a tablet or capsule.
      • The tablet or capsule comprises about 60 mg of lumateperone monotosylate with a pharmaceutically acceptable diluent or carrier.
    • The complaint alleges infringement of "one or more claims" of the ’155 Patent (Compl. ¶38).

U.S. Patent No. 12,122,792 - “Pharmaceutical Compositions Comprising 4-((6bR,10aS)-3-methyl...yl)phenyl)butan-1-one for Treating Conditions of the Central Nervous System and Cardiac Disorders”

  • Patent Identification: U.S. Patent No. 12,122,792, “Pharmaceutical Compositions Comprising 4-((6bR,10aS)-3-methyl...yl)phenyl)butan-1-one for Treating Conditions of the Central Nervous System and Cardiac Disorders,” issued October 22, 2024 (’792 Patent).
  • The Invention Explained:
    • Problem Addressed: The patent background acknowledges the existence of substituted heterocycle fused gamma-carbolines for treating CNS disorders but states that there "remains a need for additional compounds having strong serotonin receptor, serotonin transporter (SERT), and/or dopamine D₂ receptor activities" (’792 Patent, col. 2:35-40).
    • The Patented Solution: The patent claims a pharmaceutical composition that contains a mixture of two specific compounds. The first is a dimeric compound identified as "Formula I," and the second is lumateperone, identified as "Formula II" (’792 Patent, Abstract; col. 3:1-12). The invention thus claims a composition containing not just the primary active ingredient but also a specific related substance.
    • Technical Importance: This approach seeks to patent a specific compositional profile that may arise during the manufacturing of lumateperone, potentially covering the final drug product even if it contains certain specified impurities or by-products alongside the active ingredient (’792 Patent, col. 3:1-12).
  • Key Claims at a Glance:
    • The complaint asserts independent claims 1 and 29 (Compl. ¶66-67).
    • Claim 1 includes the following essential elements:
      • A pharmaceutical composition with a pharmaceutically acceptable diluent or carrier.
      • The composition contains an admixture of two compounds:
      • (i) a compound of Formula I (a lumateperone-related dimer) in free base or salt form.
      • (ii) a compound of Formula II (lumateperone) in free base or salt form.
    • Claim 29 includes the following essential elements:
      • A pharmaceutical composition comprising two compounds:
        1. a compound of Formula I in free base or salt form.
      • (ii) a compound of Formula II in toluenesulfonic acid addition salt form.
      • The weight ratio of the compound of Formula I to the compound of Formula II is in the range of 1:200 to 1:2000.
    • The complaint alleges infringement of "one or more claims" of the ’792 Patent (Compl. ¶65).

U.S. Patent No. 12,128,043 - “Pharmaceutical Capsules Comprising Lumateperone Mono-Tosylate”

  • Patent Identification: U.S. Patent No. 12,128,043, “Pharmaceutical Capsules Comprising Lumateperone Mono-Tosylate,” issued October 29, 2024 (’043 Patent).
  • Technology Synopsis: The patent is directed to specific pharmaceutical capsule formulations for oral administration. The invention claims a capsule containing lumateperone mono-tosylate in a solid crystal form, combined with specific categories of excipients, and which exhibits a defined dissolution profile in aqueous hydrochloric acid (’043 Patent, Abstract; col. 3:28-4:52).
  • Asserted Claims: The complaint asserts independent claim 1 (Compl. ¶93).
  • Accused Features: Plaintiff alleges that Defendant’s ANDA Product is a pharmaceutical capsule for oral administration comprising lumateperone mono-tosylate in solid crystal form, blended with specific diluents or carriers, and which meets the claimed dissolution parameters (Compl. ¶94).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendant Alkem’s generic lumateperone capsules, 10.5 mg, 21 mg, and 42 mg, for which it has filed ANDA No. 219200 seeking FDA approval ("Alkem’s ANDA Product") (Compl. ¶1-2).

Functionality and Market Context

  • The product is an oral capsule containing the active pharmaceutical ingredient lumateperone, a generic version of Plaintiff’s CAPLYTA® drug (Compl. ¶28). The complaint alleges that upon approval, the product will be manufactured, marketed, and sold for the treatment of schizophrenia and depressive episodes associated with bipolar disorder (Compl. ¶9, ¶26). The filing of the ANDA itself constitutes the act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶44, ¶71, ¶96). The complaint provides a chemical structure diagram for lumateperone, the active ingredient in the accused product (Compl. ¶93, p. 19).

IV. Analysis of Infringement Allegations

’155 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for the treatment of a major depressive episode associated with Bipolar II Disorder... The complaint alleges that the use of Alkem's ANDA Product as directed by its proposed label would involve treating this condition. ¶41 col. 4:35-36
...comprising administering to a patient in need thereof, a therapeutically effective amount of lumateperone in mono-tosylate salt form... Alkem's ANDA Product contains lumateperone, and its proposed label will allegedly direct its administration in a therapeutically effective amount. ¶37, ¶41 col. 5:36-39
...wherein the method comprises once daily administration of a tablet or capsule comprising about 60 mg of lumateperone mono-tosylate... Alkem's proposed label will allegedly instruct for the once-daily administration of a capsule comprising this amount. ¶41 col. 4:58-61
...in combination or association with a pharmaceutically acceptable diluent or carrier. Alkem's ANDA product is a capsule formulation that necessarily includes diluents or carriers. ¶41 col. 7:1-4
  • Identified Points of Contention:
    • Scope Questions: A central question for this method claim will be one of induced infringement. The dispute may turn on whether Alkem's proposed product labeling will specifically instruct or encourage medical professionals and patients to administer the drug for the treatment of "a major depressive episode associated with Bipolar II Disorder," as recited in the claim. The complaint alleges this based on "information and belief" (Compl. ¶41).
    • Technical Questions: The claim recites "about 60 mg of lumateperone mono-tosylate." A potential point of contention could be whether Defendant's 42 mg dosage (lumateperone free base) falls within the scope of "about 60 mg" of the salt form, an issue that may depend on evidence regarding bioequivalence and standard industry variance.

’792 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier in admixture with: Alkem's ANDA Product is alleged to be a pharmaceutical composition containing a diluent or carrier. ¶68 col. 5:3-6
(i) a compound of Formula I... in free base or pharmaceutically acceptable salt form; and The complaint alleges on "information and belief" that Alkem's ANDA Product contains the compound of Formula I. The complaint includes a diagram of the chemical structure for Formula I (Compl. ¶66, p. 14). ¶68 col. 3:1-12
(ii) a compound of Formula II... in free base or pharmaceutically acceptable salt form. Alkem's ANDA Product contains lumateperone (Formula II). The complaint includes a diagram of the chemical structure for Formula II (Compl. ¶66, p. 15). ¶64, ¶68 col. 3:1-12
  • Identified Points of Contention:
    • Scope Questions: The dispute will likely focus on a factual question of claim scope application: does Alkem’s final, manufactured ANDA Product actually contain the "compound of Formula I" as required by the claim?
    • Technical Questions: A key evidentiary question will be one of compositional identity. Plaintiff may need to present evidence, likely through chemical analysis of Defendant's product, demonstrating the presence of the Formula I compound. Defendant may argue that its manufacturing process is sufficiently pure to avoid or remove this compound, which the patent suggests is a by-product of lumateperone synthesis.

V. Key Claim Terms for Construction

  • The Term: "about 60 mg" (’155 Patent, Claim 1)
    • Context and Importance: This term defines the dosage amount in a method claim. The infringement analysis will depend on whether Defendant's product, which contains 42 mg of lumateperone free base, is considered to deliver "about 60 mg" of the mono-tosylate salt form. Practitioners may focus on this term to dispute whether the accused product's dosage falls within the claimed range.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The use of the word "about" itself suggests the patentee did not intend to be limited to the precise value of 60 mg. The specification provides direct support by stating, "lumateperone one 42 mg daily (administered orally as 60 mg of the tosylate salt) met the primary endpoint" (’155 Patent, col. 4:58-61), explicitly linking the accused dosage strength (in free base) to the claimed amount (in salt form).
      • Evidence for a Narrower Interpretation: A party seeking a narrower construction might argue that the term "about" should be limited by the precision of the number that follows it and the context of the pharmaceutical art, potentially attempting to exclude dosages that vary by more than a certain percentage. The patent, however, does not appear to provide explicit language that would support a narrower definition.
  • The Term: "a compound of Formula I" (’792 Patent, Claim 1)
    • Context and Importance: The presence of this specific compound is a required element of the claimed composition. Infringement of the '792 patent hinges entirely on whether Defendant's product contains this compound. While the chemical identity of Formula I is not ambiguous, its alleged presence in the accused product will be the central point of contention.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The term itself is not broad; it defines a specific chemical entity. A patentee would argue the claim is clear and covers any composition containing this exact molecule, regardless of amount (for claim 1) or within a specified ratio (for claim 29).
      • Evidence for a Narrower Interpretation: A defendant would likely not contest the definition of the compound but would argue that its product does not contain it. The dispute is therefore less about claim construction and more about the factual application of the construed claim to the accused product. The patent specification identifies the compound as a by-product, which a defendant might use to argue that a product manufactured under conditions of high purity would not be expected to contain it. (’792 Patent, col. 3:1-5).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement of infringement for all three patents. The basis for this allegation is Defendant’s proposed product labeling, which will allegedly instruct physicians and patients to use the generic product in an infringing manner (Compl. ¶48, ¶75, ¶100). The complaint also pleads contributory infringement, alleging the accused product is not a staple article of commerce and is not suitable for substantial noninfringing use (Compl. ¶49, ¶76, ¶101).
  • Willful Infringement: Willfulness is alleged for all three patents based on Defendant’s purported "full knowledge" of the patents and proceeding "without a reasonable basis for believing that it would not be liable for infringement" (Compl. ¶52, ¶79, ¶104). The complaint suggests this knowledge arises from Defendant’s notice letters and the ongoing, related patent litigation between the parties.

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

  • A core issue will be one of compositional identity: does Alkem’s ANDA product, as it will be commercially manufactured, contain the specific dimeric by-product ("compound of Formula I") required by the ’792 patent, or is this a trace substance that Defendant can demonstrate is absent from its final drug product?
  • A second central question will be one of induced infringement: for the ’155 patent’s method claims, does Alkem's proposed product label provide instructions that are specific enough to encourage physicians to prescribe, and patients to use, the drug for the claimed treatment of "Bipolar II Disorder"?
  • Finally, a key evidentiary question for the ’043 patent will be one of formulation equivalence: does the combination of excipients in Alkem's product and its resulting dissolution characteristics fall squarely within the specific quantitative and qualitative limitations recited in the asserted composition claim?