DCT
3:24-cv-10237
Intra Cellular Therapies Inc v. Hetero USA Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Intra-Cellular Therapies, Inc. (Delaware)
- Defendant: Hetero USA, Inc., Hetero Labs Ltd. Unit-V, and Hetero Labs Ltd. (Delaware/India)
- Plaintiff’s Counsel: Walsh Pizzi O'Reilly Falanga LLP; Williams & Connolly LLP
- Case Identification: 3:24-cv-10237, D.N.J., 11/01/2024
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey based on Defendant Hetero USA, Inc. having a principal place of business in the state, and because the foreign defendants are subject to personal jurisdiction in the district.
- Core Dispute: Plaintiff alleges that Defendants' Abbreviated New Drug Application (ANDA) to market a generic version of the antipsychotic drug CAPLYTA® (lumateperone) constitutes an act of infringement of three U.S. patents covering methods of use, specific pharmaceutical compositions, and capsule formulations.
- Technical Context: The technology concerns lumateperone, an atypical antipsychotic drug used for treating schizophrenia and bipolar depression, focusing on specific treatment methods, impurity profiles, and drug delivery characteristics.
- Key Procedural History: This lawsuit follows prior patent infringement actions filed by the Plaintiff against the same Defendants in March and August 2024 concerning the same ANDA but asserting different patents. Those prior cases have been consolidated, indicating an ongoing, multi-patent dispute over the planned generic entry of lumateperone.
Case Timeline
| Date | Event |
|---|---|
| 2018-08-31 | U.S. Patent No. 12,128,043 Priority Date |
| 2019-07-07 | U.S. Patent No. 12,090,155 Priority Date |
| 2019-12-11 | U.S. Patent No. 12,122,792 Priority Date |
| 2024-02-20 | Hetero sends Notice Letter regarding ANDA filing |
| 2024-03-28 | Plaintiff files first related lawsuit against Hetero |
| 2024-08-29 | Plaintiff files second related lawsuit against Hetero |
| 2024-09-17 | U.S. Patent No. 12,090,155 issues |
| 2024-10-22 | U.S. Patent No. 12,122,792 issues |
| 2024-10-29 | U.S. Patent No. 12,128,043 issues |
| 2024-11-01 | Complaint filed in present action |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 12,090,155 - "Methods," issued September 17, 2024
The Invention Explained
- Problem Addressed: The patent’s background section describes the difficulty in treating Bipolar II Disorder, noting it is frequently misdiagnosed and that existing therapies, such as the antipsychotic quetiapine or selective serotonin reuptake inhibitors (SSRIs), can be ineffective or cause significant side effects like sedation, metabolic issues, or triggering manic episodes (US12090155B2, col. 3:9 - col. 4:34).
- The Patented Solution: The invention is a method for treating major depressive episodes associated with Bipolar II Disorder by administering lumateperone. The specification highlights clinical trial results suggesting lumateperone provides this therapeutic benefit without common adverse effects like akathisia, restlessness, or increased suicidal ideation, which are associated with other antipsychotics used in treating bipolar disorders (US 12,090,155 B2, col. 5:8-28).
- Technical Importance: The claimed method provides a therapeutic option for a specific and often difficult-to-treat patient population with a potentially more favorable safety profile than existing treatments (US 12,090,155 B2, col. 4:15-34).
Key Claims at a Glance
- The complaint asserts independent claims 1 and 22 (Compl. ¶¶41-42).
- The essential elements of independent claim 1 include:
- A method for treating a major depressive episode associated with Bipolar II Disorder.
- Administering a therapeutically effective amount of lumateperone in mono-tosylate salt form.
- The method comprises once-daily administration.
- The administration is via a tablet or capsule containing about 60 mg of lumateperone mono-tosylate.
- The formulation includes a pharmaceutically acceptable diluent or carrier.
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
The Invention Explained
- Problem Addressed: The patent discloses the existence of a particular synthetic by-product, identified as "Compound 1," that can be formed during the synthesis of lumateperone (US12122792B2, col. 3:1-10). While not framed as a problem to be solved, the existence of such process-related impurities is a central consideration in pharmaceutical manufacturing and characterization.
- The Patented Solution: The invention claims a pharmaceutical composition that is defined by the co-presence of both the lumateperone active ingredient (Formula II) and the specific dimer-like by-product (Formula I) (US 12,122,792 B2, col. 26:47-55). By claiming the drug product as a mixture containing a specific, named impurity, the patent protects a particular impurity profile that may result from a specific manufacturing process.
- Technical Importance: This patenting approach may create a barrier for generic manufacturers, whose alternative synthetic routes might not produce the specific by-product of Formula I, thereby potentially designing around the patent claims.
Key Claims at a Glance
- The complaint asserts independent claims 1 and 29 (Compl. ¶¶68-69).
- The essential elements of independent claim 1 include:
- A pharmaceutical composition with a pharmaceutically acceptable diluent or carrier.
- The composition is in admixture with a compound of Formula I (the dimer-like by-product).
- The composition is also in admixture with a compound of Formula II (lumateperone).
U.S. Patent No. 12,128,043 - "Pharmaceutical Capsules Comprising Lumateperone Mono-Tosylate," issued October 29, 2024
- Technology Synopsis: This patent claims a specific solid oral dosage form of lumateperone. The invention is defined by a combination of formulation parameters, including the active ingredient's salt and crystal form, its concentration within a blend, the presence of certain classes of excipients, and a specific "in vitro" dissolution profile in an acidic medium (US12128043B2, Abstract; col. 4:1-51).
- Asserted Claims: Independent claim 1 is asserted (Compl. ¶95).
- Accused Features: The complaint alleges that Hetero’s ANDA Product is a pharmaceutical capsule that meets each of the claimed formulation and performance characteristics, including the use of lumateperone mono-tosylate in solid crystal form, specific excipients, and the claimed dissolution rates (Compl. ¶96). The complaint includes a visual depicting the chemical structure of lumateperone, which is the active ingredient in the claimed capsule (Compl. ¶95).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is "Hetero's ANDA Product," a generic version of Plaintiff's CAPLYTA® (lumateperone) capsules intended for commercialization in 10.5 mg, 21 mg, and 42 mg dosage strengths (Compl. ¶¶1, 30). Under the Hatch-Waxman Act, the filing of ANDA No. 219142 itself constitutes a technical act of infringement (Compl. ¶46).
Functionality and Market Context
The product is designed to be a bioequivalent substitute for CAPLYTA®, an approved treatment for schizophrenia and bipolar depression (Compl. ¶¶29-30). The complaint alleges that Hetero's proposed product labeling will direct its use for indications covered by the patents-in-suit (Compl. ¶¶43, 67, 94). As a generic drug, the product is positioned to compete directly with the branded version upon receiving FDA approval, which Hetero is alleged to be seeking prior to the expiration of the patents-in-suit (Compl. ¶¶1, 32).
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 product label for Hetero's ANDA Product will allegedly instruct physicians and patients to use the drug for treating this specific condition. | ¶43 | col. 4:35-37 |
| ...comprising administering...a therapeutically effective amount of lumateperone in mono-tosylate salt form... | Hetero's ANDA Product contains lumateperone mono-tosylate in a therapeutically effective amount. | ¶43 | col. 5:35-43 |
| ...wherein the method comprises once daily administration of a tablet or capsule comprising about 60 mg of lumateperone mono-tosylate... | The proposed label will allegedly direct for once-daily administration of a capsule containing a dosage equivalent to about 60 mg of the mono-tosylate salt. | ¶43 | col. 6:55-65 |
| ...in combination or association with a pharmaceutically acceptable diluent or carrier. | Hetero's ANDA Product is a capsule formulation that necessarily contains pharmaceutically acceptable diluents and/or carriers. | ¶43 | col. 7:1-10 |
- Identified Points of Contention:
- Scope Questions: A central question will be whether the language in Hetero's proposed product labeling constitutes active inducement of the specific method recited in the claims. The analysis may focus on whether the label encourages, recommends, or promotes use for "a major depressive episode associated with Bipolar II Disorder," as opposed to other, non-infringing indications.
- Technical Questions: The complaint alleges infringement based on the contents of Hetero's ANDA and its proposed labeling (Compl. ¶43). The actual language of that label, once produced in discovery, will be a key piece of evidence for determining inducement.
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: | Hetero's ANDA Product is a pharmaceutical composition formulated with diluents and carriers. | ¶70 | col. 5:3-9 |
| (i) a compound of Formula I... | Hetero's ANDA Product is alleged to contain the specific dimer-like by-product depicted as Formula I. The complaint provides a visual of this chemical structure (Compl. ¶68). | ¶70 | col. 3:15-38 |
| (ii) a compound of Formula II... | Hetero's ANDA Product contains lumateperone, the compound depicted as Formula II. The complaint also provides a visual of this chemical structure (Compl. ¶68). | ¶70 | col. 7:25-47 |
- Identified Points of Contention:
- Scope Questions: The dispute may raise the question of whether minor variations of the Formula I structure, such as different stereoisomers that might be present in Hetero's product, fall within the scope of the claim term "a compound of Formula I."
- Technical Questions: A primary factual dispute will likely be whether Hetero's product, manufactured using its own proprietary process, actually contains the specific by-product of Formula I. This raises an evidentiary question that will depend on analytical chemistry data, such as chromatography and mass spectrometry, of Hetero's product samples.
V. Key Claim Terms for Construction
For the ’155 Patent:
- The Term: "a major depressive episode associated with Bipolar II Disorder"
- Context and Importance: This term defines the entire field of use for the claimed method. Its construction is critical because infringement depends on whether Hetero's product label induces this specific use. Practitioners may focus on this term to determine if the clinical diagnosis described in the patent aligns precisely with the indications for which the accused product will be marketed.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification discusses the features of Bipolar II Disorder in general terms, consistent with its standard clinical understanding, which may support a broader construction not strictly limited to the patent's examples (US 12,090,155 B2, col. 3:23-31).
- Evidence for a Narrower Interpretation: The detailed description heavily relies on a specific Phase 3 clinical trial to demonstrate efficacy. A party could argue the term should be narrowed to the specific patient population and diagnostic criteria used in that trial (US 12,090,155 B2, col. 11:5-18, "Major Inclusion Criteria").
For the ’792 Patent:
- The Term: "a compound of Formula I"
- Context and Importance: The presence of this specific by-product is a mandatory claim element. The case may turn on the factual question of whether this compound is present in the accused product. The term's construction is important because it defines the precise chemical structure that must be found for a finding of literal infringement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim recites the compound "in free base or pharmaceutically acceptable salt form," suggesting the claim is not limited to a single form of the by-product (US 12,122,792 B2, col. 26:52-54).
- Evidence for a Narrower Interpretation: The patent depicts Formula I with specific stereochemistry (US 12,122,792 B2, col. 3:15-38). A party could argue that the term is limited to that specific stereoisomer and would not cover other isomers of the same molecular formula that might be generated in a different manufacturing process.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for all three patents. Inducement is primarily based on allegations that Hetero's proposed product labeling will instruct and encourage medical professionals and patients to use the infringing product in an infringing manner (Compl. ¶¶50, 77, 102). Contributory infringement is based on allegations that Hetero's product is not a staple commodity and is especially made or adapted for an infringing use (Compl. ¶¶51, 78, 103).
- Willful Infringement: The complaint alleges that Hetero 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. ¶¶54, 81, 106). This assertion appears to be based on Hetero's knowledge of the patents through the statutory framework of the Hatch-Waxman Act.
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of evidentiary proof: Can Plaintiff demonstrate through analytical testing that Hetero's generic product, made via its own manufacturing process, necessarily contains the specific dimer-like by-product recited in the ’792 Patent and meets the precise formulation and dissolution profile required by the ’043 Patent?
- A key legal question will be one of induced infringement: Will the final, FDA-approved language on Hetero's product label be construed as actively encouraging the specific method of treating "a major depressive episode associated with Bipolar II Disorder," thereby inducing infringement of the ’155 Patent, or will it be framed broadly enough to allow for substantial non-infringing uses?
- The case also presents a strategic question regarding the timing and layering of patent assertions. The patents-in-suit were all issued in late 2024, years after Hetero's initial ANDA submission and after prior lawsuits on other patents were already underway. The resolution of the case may depend on how this late-stage assertion of newly-issued patents impacts the established litigation landscape and the potential timeline for generic market entry.