DCT

3:24-cv-04330

Intra Cellular Therapies Inc v. Zydus Pharma USA Inc

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:24-cv-04330, D.N.J., 03/28/2024
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant Zydus Pharmaceuticals (USA) Inc. is incorporated and has its principal place of business in New Jersey, and Defendant Zydus Lifesciences Ltd. is subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's CAPLYTA® (lumateperone) capsules constitutes an act of infringement of five U.S. patents covering pharmaceutical compositions, methods of treatment, and related compounds.
  • Technical Context: The technology concerns oral capsule formulations for lumateperone, an atypical antipsychotic drug approved for the treatment of schizophrenia and bipolar depression.
  • Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following a notification letter dated February 12, 2024, in which Zydus informed Intra-Cellular Therapies of its ANDA filing containing a Paragraph IV certification, asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed.

Case Timeline

Date Event
2018-08-31 Earliest Priority Date for ’345, ’084, ’842, and ’348 Patents
2019-12-11 Earliest Priority Date for ’419 Patent
2020-06-30 U.S. Patent No. 10,695,345 Issues
2021-07-06 U.S. Patent No. 11,052,084 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
2024-02-12 Zydus sends Notice Letter to Plaintiff regarding ANDA filing
2024-03-28 Complaint Filed

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

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

  • Issued: June 30, 2020.
  • The Invention Explained:
    • Problem Addressed: The patent background describes the therapeutic utility of lumateperone, a compound that modulates serotonin and dopamine receptors, for treating a variety of central nervous system disorders, including schizophrenia and bipolar depression (’345 Patent, col. 1:25-3:14). The implicit technical problem is the creation of a stable and effective solid oral dosage form for delivering this therapeutic agent.
    • The Patented Solution: The invention provides a specific pharmaceutical capsule formulation. The solution is not merely the active ingredient, but its combination in a specific salt form (mono-tosylate) and physical state (solid crystal form) with a defined blend of four inactive ingredients, or excipients, each present within a specified weight percentage range (’345 Patent, Abstract; col. 4:55-5:2). This precise recipe is designed to create a consistent and manufacturable oral capsule.
    • Technical Importance: For drugs treating chronic CNS conditions, a consistent, stable oral formulation with predictable drug release characteristics is critical to ensure reliable therapeutic effects and patient compliance (’345 Patent, col. 8:20-29).
  • Key Claims at a Glance:
    • The complaint asserts independent claim 1 (Compl. ¶41).
    • The essential elements of claim 1 are:
      • A pharmaceutical capsule for oral administration;
      • Comprising lumateperone in mono-tosylate salt form;
      • Wherein the lumateperone mono-tosylate is in solid crystal form;
      • Wherein the capsule comprises a blend with specific weight percentage ranges: 10-30% lumateperone mono-tosylate, 60-90% mannitol, 0.5-10% croscarmellose sodium, 0.1-1% talc, and 0.1-3% magnesium stearate;
      • Filled into a gelatin capsule.
    • The complaint states that infringement is of "one or more claims," which may suggest an intent to assert dependent claims later (Compl. ¶40).

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

  • Issued: July 6, 2021.
  • The Invention Explained:
    • Problem Addressed: Similar to the ’345 Patent, this patent addresses the need for a stable and effective oral dosage form for lumateperone for treating CNS disorders (’084 Patent, col. 1:25-3:14).
    • The Patented Solution: The invention claims a pharmaceutical capsule composition that is structurally very similar to that of the ’345 Patent, using the same active ingredient, salt form, crystal form, and blend of excipients in identical weight percentage ranges. The key distinction is an added limitation that links the formulation to a specific dosage strength, requiring that the amount of lumateperone mono-tosylate in the capsule is "equivalent to 0.01 to 30 mg of lumateperone free base" (’084 Patent, Claim 1).
    • Technical Importance: This patent further refines the claimed composition by tying the specific excipient ratios to a defined therapeutic dose of the active moiety (the "free base"), a critical parameter for establishing dose-proportionality and bioequivalence for different dosage strengths (’084 Patent, col. 4:50-54).
  • Key Claims at a Glance:
    • The complaint asserts independent claim 1 (Compl. ¶67).
    • The essential elements of claim 1 are identical to claim 1 of the ’345 Patent, with the addition of one final element:
      • Wherein the capsule comprises the lumateperone mono-tosylate in an amount equivalent to 0.01 to 30 mg of lumateperone free base.
    • The complaint reserves the right to assert "one or more claims" (Compl. ¶66).

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

  • Issued: July 4, 2023 (Compl. ¶85).
  • Technology Synopsis: This patent claims a pharmaceutical capsule containing lumateperone mono-tosylate in the same excipient blend as the '345 and '084 patents. The invention here adds a functional requirement related to performance: the capsule must dissolve in an acidic solution to a specified extent within defined time intervals (e.g., at least 85% after 15 minutes) ('842 Patent, Claim 1). This ensures a predictable rate of drug release from the formulation.
  • Asserted Claims: Independent claim 1 is asserted as an example (Compl. ¶93).
  • Accused Features: Zydus's ANDA Product is accused of being a pharmaceutical capsule with the recited excipients and possessing the claimed dissolution profile (Compl. ¶94).

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

  • Issued: November 7, 2023 (Compl. ¶111).
  • Technology Synopsis: This patent claims a method of treating specific CNS disorders (those mediated by the 5-HT2A receptor, SERT, and/or dopamine D1/D2 pathways). The claimed method comprises administering the specific lumateperone capsule composition detailed in the earlier-issued patents ('348 Patent, Claim 1). This patent connects the specific formulation to its intended therapeutic application.
  • Asserted Claims: Independent claim 1 is asserted as an example (Compl. ¶119).
  • Accused Features: The complaint alleges that the use of Zydus’s ANDA Product, as will be directed by its proposed labeling for treating schizophrenia and bipolar depression, will infringe the claimed method (Compl. ¶120).

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 (Compl. ¶137).
  • Technology Synopsis: This patent is directed to a specific chemical compound, identified as Formula I, which is a dimer of lumateperone ('419 Patent, Abstract; Claim 1). Such compounds can be manufacturing byproducts, impurities, or metabolites of an active pharmaceutical ingredient, and patents on them can provide an additional layer of protection.
  • Asserted Claims: Independent claim 1 is asserted as an example (Compl. ¶145).
  • Accused Features: Plaintiff alleges, on information and belief, that Zydus's ANDA Product contains the claimed Formula I compound (Compl. ¶146).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is "Zydus’s ANDA Product," which is the subject of ANDA No. 218652 submitted to the FDA (Compl. ¶2). It comprises generic lumateperone capsules in 10.5 mg, 21 mg, and 42 mg dosage strengths (Compl. ¶2).

Functionality and Market Context

  • The product is a generic version of Plaintiff's approved drug, CAPLYTA®, and is intended for the treatment of schizophrenia and depressive episodes associated with bipolar disorder (Compl. ¶24, ¶25). As a generic, it is required to be bioequivalent to CAPLYTA® (Compl. ¶25). The complaint alleges that the product's formulation is a pharmaceutical capsule containing lumateperone mono-tosylate in solid crystal form, blended with the specific excipients recited in the asserted patents (Compl. ¶42, ¶68). The complaint includes a diagram illustrating the chemical structure of lumateperone, the active ingredient in the accused product (Compl. ¶41, p. 9). Zydus is seeking FDA approval to commercially manufacture and sell this product in the U.S. prior to the expiration of the patents-in-suit (Compl. ¶2).

IV. Analysis of Infringement Allegations

10,695,345 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical capsule for oral administration, comprising lumateperone... in mono-tosylate salt form... Zydus's ANDA Product is alleged to be a pharmaceutical capsule for oral administration containing lumateperone mono-tosylate. ¶42 col. 3:36-37
wherein the lumateperone mono-tosylate is in solid crystal form; and The lumateperone mono-tosylate in the accused product is alleged to be in solid crystal form. ¶42 col. 4:1-4
wherein the capsule comprises a blend of 10 to 30% by weight of lumateperone mono-tosylate in solid crystal form, 60 to 90% by weight of mannitol, 0.5 to 10% by weight of croscarmellose sodium, 0.1 to 1% by weight of talc, and 0.1 to 3% by weight of magnesium stearate, The accused product is alleged to comprise a blend of the same active ingredient and excipients within the recited weight percentage ranges. ¶42 col. 5:5-12
filled into a gelatin capsule. The blend in the accused product is alleged to be filled into a gelatin capsule. ¶42 col. 5:23-24
  • Identified Points of Contention:
    • Scope Questions: A central question will be whether "solid crystal form" is limited to the specific polymorph described in the patent's specification via incorporation by reference, or if it can be read more broadly to cover any crystalline form of lumateperone mono-tosylate. The outcome could determine whether a different polymorph used by Zydus would fall outside the claim's literal scope.
    • Technical Questions: Since the allegations are made on "information and belief" pending discovery, the primary technical question is factual: does the chemical analysis of Zydus's ANDA product confirm that it contains the exact blend of five specified ingredients within the claimed weight-percentage ranges? Any deviation may require Plaintiff to argue infringement under the doctrine of equivalents.

11,052,084 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
[First four limitations are materially identical to the ’345 Patent] [Allegations are materially identical to those for the ’345 Patent] ¶68 col. 4:1-30
wherein the capsule comprises the lumateperone mono-tosylate in an amount equivalent to 0.01 to 30 mg of lumateperone free base. Zydus’s ANDA Product is alleged to contain an amount of lumateperone mono-tosylate corresponding to the claimed dosage of the active free base. ¶68 col. 4:50-54
  • Identified Points of Contention:
    • Scope Questions: In addition to the points raised for the ’345 Patent, analysis may focus on the term "equivalent." Does this term require strict stoichiometric equivalence between the salt form and the free base, or could it be interpreted to mean therapeutic or bio-equivalence, which might broaden the claim's scope?
    • Technical Questions: A key factual dispute will be whether Zydus's proposed low-dose capsules (e.g., 10.5 mg) contain an amount of the lumateperone mono-tosylate that calculates to a free base amount within the claimed 0.01 to 30 mg range.

V. Key Claim Terms for Construction

  • The Term: "solid crystal form" (asserted in claims of '345, '084, '842, and '348 patents)

  • Context and Importance: The physical form of an active pharmaceutical ingredient can significantly impact its stability, dissolution, and bioavailability. Infringement requires that Zydus's product contains the claimed "solid crystal form." If Zydus developed a stable amorphous version or a novel, non-infringing polymorph (a different crystal structure), it could design around these patents. Practitioners may focus on this term because the patents' specifications repeatedly point to a specific crystal form previously disclosed in another patent.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The claim language itself does not specify a particular polymorph (e.g., by referencing specific X-ray diffraction peaks). A party could argue this means the claim covers any and all crystalline forms of lumateperone mono-tosylate.
    • Evidence for a Narrower Interpretation: The specification of the ’345 Patent states that the lumateperone mono-tosylate is in a solid crystal form "e.g., having the physical and chemical properties as disclosed in U.S. Pat. No. 8,648,077, such as one or more of the XRPD spectrum... as disclosed therein" (’345 Patent, col. 4:4-8). A party would argue this language defines and limits the claimed "solid crystal form" to the specific polymorph characterized in the '077 patent.

  • The Term: "a blend of" (followed by weight percentages) (asserted in claims of '345, '084, '842, and '348 patents)

  • Context and Importance: This term is critical as it defines the quantitative relationship between the five components of the claimed composition. The case will require a factual determination of whether Zydus's formulation meets these precise percentage ranges. The construction of "blend" and how percentages are measured (e.g., accounting for moisture content) could be dispositive.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The term "blend" is not explicitly defined, suggesting its plain and ordinary meaning of a mixture. The specification describes a manufacturing process of "dry blending" the components, which supports a straightforward interpretation of mixing the listed ingredients (’345 Patent, col. 11:39-44).
    • Evidence for a Narrower Interpretation: A party could argue that the term should be limited by the examples provided in the specification, which disclose specific formulations and manufacturing processes (’345 Patent, col. 13:5-col. 14:15, Example 2). This may suggest that only compositions made through similar blending processes are covered, though this is generally a difficult argument to sustain for composition claims.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for all five patents. Inducement is primarily based on the allegation that Zydus’s proposed product labeling will instruct physicians and patients to use the ANDA product in an infringing manner (e.g., for the indications claimed in the '348 method patent) (Compl. ¶¶48, 74, 100, 126, 152). Contributory infringement is based on allegations that the Zydus product is not a staple article of commerce and is not suitable for a substantial non-infringing use (Compl. ¶¶49, 75, 101, 127, 153).
  • Willful Infringement: Willfulness is alleged based on Zydus having "full knowledge" of the patents-in-suit and proceeding "without a reasonable basis for believing that it would not be liable" (Compl. ¶¶52, 78, 104, 130, 156). This allegation of pre-suit knowledge is supported by Zydus’s submission of a Paragraph IV certification to the FDA, which is an explicit acknowledgment and challenge of the patents listed in the FDA's Orange Book for CAPLYTA®.

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

  • A primary issue will be evidentiary and factual: does the composition of Zydus’s ANDA Product, once revealed in discovery, fall within the specific weight percentage ranges for each excipient recited in the asserted composition claims, and does it utilize the specific "solid crystal form" of lumateperone mono-tosylate?
  • A key legal and factual question will concern induced infringement: will the proposed label for Zydus’s product instruct users to perform the patented method of treating specific CNS disorders as claimed in the ’348 patent, thereby making Zydus liable for inducing infringement by physicians and patients?
  • A critical technical question will be one of compositional identity: does Zydus's ANDA Product actually contain the specific dimeric compound of Formula I as claimed in the ’419 patent, which may exist as a manufacturing byproduct or impurity, and if so, is its presence sufficient to constitute infringement?