DCT
3:24-cv-10240
Intra Cellular Therapies Inc v. Zydus Pharma USA Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Intra-Cellular Therapies, Inc. (Delaware)
- Defendant: Zydus Pharmaceuticals (USA) Inc. (New Jersey) and Zydus Lifesciences Ltd. (India)
- Plaintiff’s Counsel: Walsh Pizzi O'Reilly Falanga LLP; Williams & Connolly LLP
- Case Identification: 3:24-cv-10240, D.N.J., 11/01/2024
- Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant Zydus Pharmaceuticals (USA) Inc. is a New Jersey corporation with its principal place of business in the state, and Defendant Zydus Lifesciences Ltd. is subject to personal jurisdiction there.
- Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of Plaintiff's drug CAPLYTA® (lumateperone) constitutes an act of infringement of three U.S. patents covering methods of use, pharmaceutical compositions, and specific formulations.
- Technical Context: The dispute centers on lumateperone, an atypical antipsychotic drug approved for treating schizophrenia and depressive episodes associated with bipolar disorder.
- Key Procedural History: The complaint notes that this lawsuit is one of several related and consolidated actions between the parties concerning Defendants' ANDA submission for generic lumateperone, with prior suits filed in March and August 2024 involving different patents.
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 |
| 2024-02-12 | Zydus sends Notice Letter to Plaintiff regarding ANDA filing |
| 2024-03-28 | Plaintiff files first related lawsuit against Zydus |
| 2024-08-29 | Plaintiff files second related lawsuit against Zydus |
| 2024-09-17 | ’155 Patent Issues |
| 2024-10-22 | ’792 Patent Issues |
| 2024-10-29 | ’043 Patent Issues |
| 2024-11-01 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 12,090,155 - "Methods"
The Invention Explained
- Problem Addressed: The patent's background section describes a need for safer and more effective treatments for Bipolar II Disorder, noting that it is often misdiagnosed and that existing antipsychotics can have significant side effects, including sedation, metabolic issues, or triggering of manic episodes (U.S. Patent No. 12,090,155, col. 3:24-4:4).
- The Patented Solution: The invention claims a method of treating depressive episodes associated with Bipolar II Disorder by administering lumateperone. The patent asserts that clinical trials showed lumateperone to be not only effective for this indication but also to have a favorable safety profile, avoiding common side effects like movement disorders (akathisia), metabolic issues, or suicidal ideation often associated with other treatments (’155 Patent, col. 4:34-46, col. 5:14-28).
- Technical Importance: The invention provides a targeted method of treatment for a specific patient population (Bipolar II) that was allegedly underserved by existing therapies, offering a potential for efficacy without certain debilitating side effects (’155 Patent, col. 4:26-31).
Key Claims at a Glance
- The complaint asserts independent claims 1 and 22 ('155 Patent, col. 14:50-59, col. 15:14-23; Compl. ¶¶38-39).
- Claim 1, asserted as an example, contains the following essential elements:
- A method for the treatment of a major depressive episode associated with Bipolar II Disorder.
- Comprising administering to a patient a therapeutically effective amount of lumateperone in mono-tosylate salt form.
- Wherein the method comprises once daily administration of a tablet or capsule.
- The tablet or capsule comprises about 60 mg of lumateperone mono-tosylate in combination or association with a pharmaceutically acceptable diluent or carrier.
U.S. Patent No. 12,122,792 - "Pharmaceutical Compositions Comprising 4-((6bR,10aS)-3-methyl...[etc.]...butan-1-one for Treating Conditions of the Central Nervous System and Cardiac Disorders"
The Invention Explained
- Problem Addressed: The patent background states there "remains a need for additional compounds having strong serotonin receptor, serotonin transporter (SERT), and/or dopamine D₂ receptor activities" for treating various central nervous system disorders (’792 Patent, col. 2:34-38).
- The Patented Solution: The invention is a specific chemical compound, identified as Formula I, which is a dimer of lumateperone. The patent discloses that this compound, a synthetic by-product, was "unexpectedly found to have potent affinity for, or activity at," a unique combination of neurological receptors, including serotonin transporters, dopamine receptors, sodium channels, and norepinephrine transporters, making it a candidate for treating neurological and psychiatric disorders (’792 Patent, col. 3:1-9, Abstract).
- Technical Importance: The invention identifies a novel chemical entity with a unique pharmacological profile, suggesting its potential utility in treating a range of complex neurological conditions beyond those addressed by its monomer precursor, lumateperone (’792 Patent, col. 1:21-2:2).
Key Claims at a Glance
- The complaint asserts independent claims 1 and 29 as examples (’792 Patent, col. 26:50-27:2, col. 29:1-9; Compl. ¶¶65-66).
- Claim 1, asserted as an example, contains the following essential elements:
- A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier in admixture with:
- (i) a compound of Formula I (the lumateperone dimer).
- (ii) a compound of Formula II (lumateperone).
U.S. Patent No. 12,128,043 - "Pharmaceutical Capsules Comprising Lumateperone Mono-Tosylate"
- Technology Synopsis: The patent addresses the need for a specific, stable, and effective oral dosage form of lumateperone. It claims a pharmaceutical capsule containing lumateperone mono-tosylate in a solid crystal form, combined with specific types of excipients, and which meets defined dissolution rate parameters, ensuring proper release of the active ingredient in the body (’043 Patent, col. 4:1-50:3).
- Asserted Claims: The complaint asserts independent claim 1 as an example (Compl. ¶92).
- Accused Features: The complaint alleges that Zydus's ANDA Product is a pharmaceutical capsule containing lumateperone mono-tosylate in solid crystal form, blended with the claimed types of diluents or carriers, and meets the claimed dissolution parameters (Compl. ¶93).
III. The Accused Instrumentality
Product Identification
- "Zydus's ANDA Product," a generic version of CAPLYTA® (lumateperone) capsules proposed for marketing in 10.5 mg, 21 mg, and 42 mg dosages (Compl. ¶¶1-2).
Functionality and Market Context
- The accused product is a pharmaceutical formulation containing lumateperone, intended for oral administration (Compl. ¶¶27, 36). As a generic version of CAPLYTA®, it is intended to be used for the same FDA-approved indications, which include the treatment of schizophrenia and depressive episodes associated with bipolar disorder (Compl. ¶¶26-27). The complaint alleges that Zydus's submission of ANDA No. 218652 seeks approval to commercially manufacture and sell this product prior to the expiration of the patents-in-suit (Compl. ¶2).
IV. Analysis of Infringement Allegations
U.S. Patent No. 12,090,155 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 proposed label for Zydus's ANDA Product would allegedly direct its use for treating a major depressive episode associated with Bipolar II Disorder. | ¶40 | col. 1:5-10 |
| ...comprising administering to a patient in need thereof, a therapeutically effective amount of lumateperone in mono-tosylate salt form... | Zydus's ANDA Product contains lumateperone, and its proposed label would direct administration of a therapeutically effective amount. | ¶¶36, 40 | col. 4:50-54 |
| ...wherein the method comprises once daily administration of a tablet or capsule... | Zydus's ANDA Product is a capsule, and its proposed label would allegedly direct once daily administration. | ¶¶27, 40 | col. 7:5-10 |
| ...comprising about 60 mg of lumateperone mono-tosylate in combination or association with a pharmaceutically acceptable diluent or carrier. | Zydus's ANDA Product is a capsule comprising a dosage equivalent to the claimed amount, in combination with a diluent or carrier. | ¶40 | col. 7:5-10 |
- Identified Points of Contention:
- Scope Questions: The case may turn on whether Zydus's proposed product labeling will be found to explicitly instruct or encourage physicians and patients to perform every step of the claimed method, particularly the treatment of the specific Bipolar II Disorder population as required by the claim.
- Technical Questions: A potential question is whether the dosage in Zydus's ANDA Product, which corresponds to 42 mg of lumateperone free base, falls within the scope of "about 60 mg of lumateperone mono-tosylate" as recited in the claim.
U.S. Patent No. 12,122,792 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: | Zydus's ANDA Product is alleged to be a pharmaceutical composition containing diluents and/or carriers. | ¶67 | col. 9:1-5 |
| (i) a compound of Formula I...in free base or pharmaceutically acceptable salt form; and | The complaint alleges on information and belief that Zydus's ANDA Product contains the dimer compound of Formula I, which is depicted in a chemical structure diagram. The diagram in the complaint illustrates the specific dimer compound of Formula I. | ¶¶65, 67 | col. 7:50-8:15 |
| (ii) a compound of Formula II...in free base or pharmaceutically acceptable salt form. | Zydus's ANDA Product contains lumateperone, the compound of Formula II. | ¶¶63, 67 | col. 8:20-35 |
- Identified Points of Contention:
- Scope Questions: A central question will be whether the presence of the Formula I dimer as a potential impurity or uncharacterized component in a generic drug product is sufficient to meet the claim limitation "comprising... a compound of Formula I," or if the claim requires its intentional inclusion as part of the "pharmaceutical composition."
- Technical Questions: The primary technical question is a factual one: what evidence exists that Zydus's ANDA Product actually contains the specific dimer compound of Formula I? The complaint pleads this on "information and belief," suggesting this will be a key area for discovery and proof.
V. Key Claim Terms for Construction
’155 Patent
- The Term: "about 60 mg of lumateperone mono-tosylate"
- Context and Importance: This term is critical because infringement depends on whether the dosage of the accused generic product falls within its scope. The branded product, CAPLYTA®, is marketed based on its free base amount (42 mg), which is equivalent to 60 mg of the tosylate salt. Practitioners may focus on this term to determine if Zydus's corresponding dosage meets this limitation.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The use of the word "about" suggests the patentee did not intend to be limited to exactly 60 mg. The specification consistently equates "42 mg" of the free base with the tosylate salt form, and the clinical trial data is based on this dose, which may support construing "about 60 mg" of the salt to encompass the amount equivalent to 42 mg of the free base (’155 Patent, col. 9:60-61).
- Evidence for a Narrower Interpretation: A defendant could argue that "about" still implies a narrow numerical range and does not cover any amount that is merely bioequivalent. The patent does not provide an explicit numerical range for "about," raising the question of how much deviation from "60 mg" is permissible.
’792 Patent
- The Term: "a compound of Formula I"
- Context and Importance: The infringement allegation for the '792 patent hinges entirely on the presence of this specific dimer compound in the accused product. Practitioners may focus on this term because the compound is described in the patent as a synthetic by-product, and its alleged presence in Zydus's generic product is a core factual allegation made on information and belief.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim uses the open-ended term "comprising," which typically means the claimed composition must contain the listed elements but does not exclude others. The claim does not specify a minimum amount or purity level for the "compound of Formula I," which could support an argument that its presence in any detectable amount satisfies the limitation.
- Evidence for a Narrower Interpretation: The specification identifies Formula I as a "synthetic by-product in the synthesis of lumateperone" (’792 Patent, col. 3:6-8). A defendant may argue that this context implies the term should be construed to mean an intentionally included component of a composition, not an unintended, trace-level process impurity that is not part of the product's specification.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for all three patents-in-suit. The inducement allegations are based on the assertion that Zydus's proposed product labeling will instruct and encourage medical professionals and patients to use the generic product in an infringing manner (Compl. ¶¶47, 74, 99). The contributory infringement allegations are based on the assertion that Zydus knows its product is especially made or adapted for an infringing use and is not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶¶48, 75, 100).
- Willful Infringement: The complaint alleges willful infringement for all patents-in-suit, asserting that Zydus has acted with "full knowledge" of the patents and "without a reasonable basis for believing that it would not be liable for infringement" (Compl. ¶¶51, 78, 103). The basis for knowledge appears to be Zydus's own Notice Letter identifying the patents in its ANDA certification process (Compl. ¶2).
VII. Analyst’s Conclusion: Key Questions for the Case
This Hatch-Waxman litigation presents several distinct questions across the asserted patents that will be central to the dispute's resolution.
- A primary issue will be one of factual evidence: for the ’792 patent, can Plaintiff prove that the accused generic product contains the specific lumateperone dimer of "Formula I" as alleged? The outcome of this claim may depend entirely on chemical analysis conducted during discovery.
- A second core issue will be one of induced infringement: for the method claims of the ’155 patent, does Zydus's proposed product label contain instructions that are specific enough to direct prescribers and patients to perform every step of the claimed method of treating depressive episodes specifically associated with Bipolar II Disorder?
- A third key question will be one of claim scope and technical performance: for the formulation claims of the ’043 patent, does the accused product's composition and in vitro dissolution profile literally meet the quantitative limitations recited in the claims, including the percentage of active ingredient, the types of excipients, and the specific dissolution rates over time?