DCT

3:25-cv-15276

Jazz Pharma Ireland Ltd v. Invagen Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:25-cv-15276, D.N.J., 09/04/2025
  • Venue Allegations: Plaintiffs allege venue is proper in the District of New Jersey because multiple defendants maintain a regular and established place of business in the district, conduct continuous business activities there, and have previously consented to venue in the district in related litigation involving the same Abbreviated New Drug Applications (ANDAs). For foreign defendants, venue is alleged to be proper in any judicial district.
  • Core Dispute: Plaintiffs allege that Defendants' submission of ANDAs to the U.S. Food and Drug Administration (FDA) to market generic versions of the cancer drug Zepzelca® (lurbinectedin) constitutes an act of infringement of a patent covering a method for treating small cell lung cancer while managing drug-induced liver toxicity.
  • Technical Context: The technology concerns a specific dose-modification regimen for the chemotherapy agent lurbinectedin, designed to allow continued treatment for patients who experience severe liver-related side effects.
  • Key Procedural History: This action arises under the Hatch-Waxman Act following Defendants' submission of ANDAs with Paragraph IV certifications challenging the patent-in-suit. The complaint notes that the ANDAs were previously the subject of litigation concerning a different patent.

Case Timeline

Date Event
2019-11-21 ’806 Patent Priority Date
2020-06-15 FDA grants accelerated approval for Zepzelca® (lurbinectedin) NDA
2025-06-10 ’806 Patent Issues
2025-07-22 InvaGen sends Notice Letter regarding the ’806 Patent
2025-09-04 Complaint Filed

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

U.S. Patent No. 12,324,806 - Method of Treating SCLC and Managing Hepatotoxicity

  • Patent Identification: U.S. Patent No. 12,324,806 (“the ’806 Patent”), Method of Treating SCLC and Managing Hepatotoxicity, issued June 10, 2025.

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of treating small cell lung cancer (SCLC), an aggressive malignancy where patients often relapse after initial chemotherapy (’806 Patent, col. 1:20-44). While the drug lurbinectedin offers a second-line treatment option, it can cause significant adverse events, including hematological toxicity and hepatotoxicity (liver damage), which can force discontinuation of the therapy (’806 Patent, col. 4:5-9).
  • The Patented Solution: The patent discloses a method for managing hepatotoxicity to allow for continued treatment. The solution is a specific dose-adjustment protocol: if a patient experiences severe (≥ Grade 3) hepatotoxicity after a standard 3.2 mg/m² dose, subsequent treatment cycles should use a reduced dose of 2.6 mg/m². This reduced dose is only administered after the patient's liver function has recovered (≤ Grade 1 hepatotoxicity) and other key blood metrics (platelets, neutrophils) have returned to safe levels, and within a specified time window (’806 Patent, col. 108:5-col. 109:11; Abstract). This method allows for the continuation of an effective cancer therapy while mitigating a dose-limiting toxicity.
  • Technical Importance: This dose-modification strategy provides a defined protocol for physicians to safely continue treating SCLC patients with lurbinectedin who might otherwise have to abandon the therapy due to severe side effects, thereby balancing efficacy and safety (’806 Patent, col. 4:5-9).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims," with a focus on independent claim 1 (Compl. ¶177).
  • Independent Claim 1:
    • A method of treating metastatic small cell lung cancer (SCLC) in a patient with disease progression after platinum-based chemotherapy;
    • Said method comprising administering, within 35 days of receiving a dose of 3.2 mg/m² of lurbinectedin, a dose of 2.6 mg/m² of lurbinectedin;
    • To a patient having at the time of the 2.6 mg/m² dose administration: a) metastatic SCLC with disease progression after platinum-based chemotherapy, b) a platelet count of at least 100,000/mm³, c) an absolute neutrophil count of at least 1500 cells/mm³, and d) ≤ Grade 1 hepatotoxicity;
    • Wherein the patient previously experienced ≥ Grade 3 hepatotoxicity subsequent to receiving the 3.2 mg/m² dose.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are the generic "Lurbinectedin for injection, 4 mg/vial" products for which Defendants have filed ANDA Nos. 219605, 219515, 219582, 219731, and 219771 (Compl. ¶48, 135, 148, 154, 160, 166). The complaint identifies the chemical structure of lurbinectedin (Compl. ¶129).

Functionality and Market Context

  • The complaint alleges that Defendants seek FDA approval to market their generic lurbinectedin products for the same indication as Plaintiffs' branded product, Zepzelca®: the "treatment of adult patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy" (Compl. ¶137, 150, 156, 162, 168). The infringement allegation centers on the proposed labeling for these generic products. The complaint alleges these labels will contain instructions for use that "substantially copy the instructions for Zepzelca®" and will direct medical professionals to practice the patented method of dose reduction in response to hepatotoxicity (Compl. ¶179, 206, 232, 258, 284).

IV. Analysis of Infringement Allegations

U.S. Patent No. 12,324,806 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating metastatic small cell lung cancer (SCLC) in a patient with disease progression after platinum-based chemotherapy... The complaint alleges that the proposed labeling for Defendants' generic products will direct their use for the treatment of patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy. ¶179 col. 108:50-52
...said method comprising administering, within 35 days of receiving a dose of 3.2 mg/m² of lurbinectedin by intravenous infusion as a monotherapy, a dose of 2.6 mg/m² lurbinectedin by intravenous infusion as a monotherapy... The complaint alleges the proposed labeling will direct administering a reduced dose of 2.6 mg/m² lurbinectedin following a patient experiencing Grade ≥3 hepatotoxicity at the 3.2 mg/m² dose, and will direct this administration "within 35 days of receiving a 3.2 mg/m² dose of lurbinectedin." ¶179 col. 108:53-61
...to a patient having at the time of the administration of the dose of 2.6 mg/m² of lurbinectedin: a) metastatic SCLC..., b) a platelet count of at least 100,000/mm³, c) an absolute neutrophil count of at least 1500 cells/mm³, and d) ≤ Grade 1 hepatotoxicity; The complaint alleges the proposed labeling will instruct that the reduced dose of 2.6 mg/m² lurbinectedin be administered only when the patient has recovered to a state meeting these specific criteria, including a platelet count of at least 100,000/mm³, an absolute neutrophil count of at least 1500 cells/mm³, and Grade ≤1 hepatotoxicity. ¶179 col. 109:1-5
...wherein the patient previously experienced ≥ Grade 3 hepatotoxicity subsequent to receiving the dose of 3.2 mg/m² of lurbinectedin. The complaint alleges the proposed labeling will identify Grade ≥3 hepatotoxicity as an adverse reaction to treatment with the 3.2 mg/m² dose and will direct the dose reduction as the appropriate medical response to this specific event. ¶179 col. 109:6-11

Identified Points of Contention

  • Scope Questions: The central dispute will likely be whether the language of Defendants’ proposed labels actively induces infringement under 35 U.S.C. § 271(b). A question for the court may be whether the label merely informs physicians of a potential side effect and a possible dose modification, or if it specifically instructs, encourages, and recommends the full, multi-step method recited in claim 1, thereby creating liability for inducement.
  • Technical Questions: A key evidentiary question will be the degree to which Defendants’ proposed labels mirror the label for the branded drug, Zepzelca®. The complaint alleges the labels "substantially copy" the Zepzelca® instructions (Compl. ¶179). The extent of this copying will be a factual determination central to the question of whether the label directs physicians to perform the patented method.

V. Key Claim Terms for Construction

  • The Term: "≤ Grade 1 hepatotoxicity"

    • Context and Importance: This term defines a critical condition for the patient before the reduced dose can be administered. Its construction is important because if a defendant's proposed label defines the patient's recovery state using different or ambiguous criteria, it may support a non-infringement defense. Practitioners may focus on whether this term requires specific laboratory values or allows for more general clinical judgment.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent specification explicitly incorporates by reference the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0, which provides standardized definitions for toxicity grades ('806 Patent, col. 8:50-65). This may support an argument that the term should be given its broad, accepted meaning in the field of oncology.
      • Evidence for a Narrower Interpretation: The detailed description of the clinical trial (Example 8) provides specific criteria for re-treatment after adverse events, which could be used to argue for a narrower construction tied to the specific parameters measured in the trial, such as AST/ALT and bilirubin levels ('806 Patent, Table 13, col. 57).

  • The Term: "previously experienced ≥ Grade 3 hepatotoxicity"

    • Context and Importance: This phrase is the trigger for the entire claimed method. The definition of what constitutes "experiencing" this event—for instance, the duration, the specific diagnostic criteria, or whether a single elevated lab value is sufficient—will be central to determining the scope of the claim.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent's general discussion of dose modifications for adverse reactions suggests that any clinically recognized Grade 3 or 4 hepatotoxicity event, as defined by the incorporated NCI CTCAE standard, would satisfy this limitation ('806 Patent, col. 16:21-44).
      • Evidence for a Narrower Interpretation: The detailed descriptions of dose modifications for other toxicities, such as neutropenia and thrombocytopenia, are highly specific ('806 Patent, col. 17:1-col. 18:24). A party could argue that "hepatotoxicity" should be construed with similar specificity, limited to the types of events documented and managed in the patent's clinical trial examples.

VI. Other Allegations

  • Indirect Infringement: The core of the complaint is inducement of infringement under 35 U.S.C. § 271(b). Plaintiffs allege Defendants have knowledge of the ’806 Patent via its listing in the FDA's Orange Book and, in at least one case, a direct notice letter (Compl. ¶174, 138). They allege Defendants intend for infringement to occur by seeking FDA approval for a product with a proposed label that allegedly instructs and encourages medical professionals to perform every step of the patented method (Compl. ¶179, 183).
  • Willful Infringement: The complaint alleges that Defendants were aware of the ’806 Patent at the time of their ANDA submissions, or became aware shortly thereafter, and proceeded despite this knowledge (Compl. ¶174, 201, 227, 253, 279). It seeks a declaration that the case is "exceptional" under 35 U.S.C. § 285, which is the statutory basis for awarding attorney's fees and is often predicated on a finding of willful infringement (Compl. ¶185; Prayer for Relief ¶G).

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

  • A core issue will be one of inducement and label interpretation: does the specific language in the Defendants' proposed product labels actively instruct and encourage physicians to perform the complete, multi-step dose-reduction method of Claim 1, or does the label merely provide optional guidance for managing a potential side effect in a manner that falls short of directing the patented method?
  • A key evidentiary question will be one of factual equivalence: to what extent does the text of the proposed generic labels "substantially copy" the label of the branded drug, Zepzelca®? The degree of similarity will be a central fact in determining whether the label provides the specific instructions necessary to find inducement of the claimed method.
  • A secondary issue may be one of definitional scope: will the clinical criteria recited in the claim, such as "≥ Grade 3 hepatotoxicity," be construed according to the broad industry standards incorporated by reference in the patent, or will they be limited to the specific clinical endpoints and measurement techniques detailed in the patent's own clinical trial examples?