DCT

2:25-cv-03945

Pharmacosmos As v. Hetero Labs Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:25-cv-03945, D.N.J., 05/07/2025
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant Hetero USA maintains its principal place of business in New Jersey and prepared and submitted the accused Abbreviated New Drug Application (ANDA) from the state. Venue over the foreign-domiciled Hetero entities is alleged based on their control over Hetero USA and their purposeful availment of doing business in New Jersey.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an ANDA to market a generic version of Plaintiff's cancer therapy drug COSELA® (trilaciclib) infringes two U.S. patents covering a specific method of administering the drug in conjunction with chemotherapy and particular morphic forms of the drug compound itself.
  • Technical Context: The technology relates to adjunct therapies in oncology designed to mitigate the harmful side effects of chemotherapy, specifically myelosuppression (damage to bone marrow and immune cells), thereby improving the efficacy of combination chemo-immunotherapy regimens.
  • Key Procedural History: This Hatch-Waxman action was initiated following Plaintiff’s receipt on March 27, 2025, of a Paragraph IV Notice Letter from Defendant, which provided notice of the filing of ANDA No. 220282 seeking approval to market a generic version of trilaciclib prior to the expiration of the patents-in-suit.

Case Timeline

Date Event
2016-12-05 U.S. Patent No. 11,529,352 Priority Date
2020-06-15 U.S. Patent No. 12,168,666 Priority Date
2021-02-12 FDA Approval of COSELA® (NDA No. 214200)
2022-12-20 U.S. Patent No. 11,529,352 Issues
2024-12-17 U.S. Patent No. 12,168,666 Issues
2025-03-25 Hetero's Paragraph IV Notice Letter Sent
2025-03-27 Pharmacosmos Receives Paragraph IV Notice Letter
2025-05-07 Complaint Filed

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

U.S. Patent No. 11,529,352 - "Preservation of Immune Response During Chemotherapy Regimens"

  • Patent Identification: U.S. Patent No. 11,529,352, "Preservation of Immune Response During Chemotherapy Regimens", issued December 20, 2022.

The Invention Explained

  • Problem Addressed: The patent’s background section describes a conflict in combination cancer therapies: while combining chemotherapy with immune checkpoint inhibitors can be effective, the chemotherapy itself often damages the very immune cells (such as T-lymphocytes) that the checkpoint inhibitors are meant to activate, thereby diminishing the overall therapeutic efficacy ( Compl. ¶39; ’352 Patent, col. 1:11-17).
  • The Patented Solution: The invention proposes a specifically-timed administration of a selective, fast-acting, short half-life Cyclin-Dependent Kinase 4/6 (CDK4/6) inhibitor. By administering this inhibitor shortly before each dose of chemotherapy, it temporarily arrests the patient's immune and hematopoietic cells in a phase of the cell cycle where they are less susceptible to damage from the cytotoxic chemotherapy. This preserves the immune system's integrity, allowing it to respond more robustly when stimulated by the immune checkpoint inhibitor portion of the regimen (’352 Patent, Abstract; col. 2:20-24; col. 4:1-14).
  • Technical Importance: This method provides a way to uncouple the cell-killing effects of chemotherapy on cancer cells from its damaging effects on immune cells, potentially enhancing the synergy between chemotherapy and immunotherapy treatments (Compl. ¶39).

Key Claims at a Glance

  • The complaint asserts infringement of Claim 1, an independent method claim (Compl. ¶70).
  • The essential elements of Claim 1 are:
    • A method of treating cancer in a human with a therapeutic regimen comprising an "induction phase" and a "maintenance phase."
    • The induction phase comprises administering: (i) a specific CDK4/6 inhibitor (trilaciclib), (ii) a chemotherapeutic agent cytotoxic to immune cells, and (iii) an immune checkpoint inhibitor.
    • A timing limitation wherein the CDK4/6 inhibitor is administered "only 24 hours or less prior to" the chemotherapeutic agent during the induction phase.
    • The maintenance phase comprises administering at least one dose of the immune checkpoint inhibitor and occurs after the induction phase has ceased.
  • The complaint alleges that the use of Hetero's product will infringe "one or more claims" of the ’352 patent, reserving the right to assert other claims (Compl. ¶69).

U.S. Patent No. 12,168,666 - "Morphic Forms of Trilaciclib And Methods of Manufacture Thereof" (Multi-Patent Capsule)

  • Patent Identification: U.S. Patent No. 12,168,666, "Morphic Forms of Trilaciclib And Methods of Manufacture Thereof", issued December 17, 2024.

Technology Synopsis

This patent addresses the technical challenge of producing the drug trilaciclib in a stable, highly purified, and manufacturable solid form. The invention discloses specific crystalline structures, or "morphic forms," of trilaciclib, such as a dihydrochloride dihydrate form designated "Pattern 1," which is described as having advantageous properties for formulation, particularly for the intravenous solutions required for administration (’666 Patent, col. 2:1-20, col. 2:44-53).

Asserted Claims

The complaint does not identify specific claims of the ’666 Patent, alleging generally that Hetero's product will infringe "one or more claims" (Compl. ¶89).

Accused Features

The infringement allegation is directed at the commercial manufacture and sale of Hetero's ANDA Product itself (Compl. ¶89-91). This suggests the drug product, as a composition of matter, is alleged to be or contain a claimed morphic form of trilaciclib.

III. The Accused Instrumentality

Product Identification

  • Hetero's ANDA Product is an injectable, intravenous generic version of Pharmacosmos' COSELA® (trilaciclib) (Compl. ¶1). The ANDA number is 220282 (Compl. ¶1).

Functionality and Market Context

  • The product is a generic trilaciclib formulation intended for use as a kinase inhibitor to "decrease the incidence of chemotherapy-induced myelosuppression in adult patients" undergoing certain chemotherapy regimens for small cell lung cancer (Compl. ¶39). The complaint alleges that Hetero's ANDA Product will be accompanied by labeling that is "substantially identical" to the prescribing information for COSELA®, which instructs its administration as a "30-minute intravenous infusion completed no more than 4 hours prior to the start of chemotherapy" (Compl. ¶40, ¶67). This proposed instruction is central to the allegations of induced infringement of the ’352 Patent.

IV. Analysis of Infringement Allegations

’352 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating a human having cancer comprising administering to the human a therapeutic regimen comprising a) an induction phase and b) a maintenance phase, Use of Hetero's ANDA product as directed by its proposed labeling will constitute a method of treating cancer, which the labeling allegedly divides into induction and maintenance phases based on the COSELA® regimen. ¶71, ¶41 col. 6:1-10
a) the induction phase comprising: i) administering to the human an effective amount of a selective Cyclin Dependent Kinase 4/6 (CDK4/6) inhibitor of structure: [image] or a pharmaceutically acceptable salt thereof, Hetero's product contains trilaciclib, which is the CDK4/6 inhibitor with the specified chemical structure. The complaint provides an image of the chemical structure for the selective Cyclin Dependent Kinase 4/6 (CDK4/6) inhibitor recited in the claim (Compl. ¶70). ¶50, ¶70 col. 7:55-65
ii) administering to the human an effective amount of a chemotherapeutic agent, The proposed labeling will direct co-administration with chemotherapeutic agents such as platinum/etoposide. ¶39, ¶67-68 col. 5:65-67
iii) administering to the human an effective amount of an immune checkpoint inhibitor, The proposed labeling will direct co-administration with an immune checkpoint inhibitor such as atezolizumab. ¶41, ¶67-68 col. 6:1-2
wherein, during the induction phase, the CDK4/6 inhibitor is only administered 24 hours or less prior to the administration of the chemotherapeutic agent... The COSELA® label, which Hetero's label allegedly mirrors, instructs administration "no more than 4 hours prior to the start of chemotherapy," satisfying the "24 hours or less prior" limitation. ¶40, ¶67 col. 6:2-5
...and wherein the chemotherapeutic agent is cytotoxic to immune effector cells; Standard chemotherapeutic agents used in the indicated regimens, such as etoposide and carboplatin, are alleged to be cytotoxic to immune cells. ¶70 col. 1:11-15
b) the maintenance phase comprising: i) administering to the human at least one dose of an effective amount of the immune checkpoint inhibitor, and wherein the maintenance phase is administered following the cessation of the induction phase. The proposed labeling will direct a maintenance phase consisting of administering the immune checkpoint inhibitor after the induction cycles are complete. ¶41, ¶67 col. 6:5-10

Identified Points of Contention

  • Scope Questions: A potential point of dispute may be the interpretation of "only administered... prior to." A defendant could argue that if the CDK4/6 inhibitor is alleged to have any therapeutic effect beyond myeloprotection, or if its administration window could be construed differently, this limitation might not be met.
  • Technical Questions: The infringement theory for the ’352 Patent is one of inducement, which depends entirely on the instructions in Hetero's proposed product labeling. The central evidentiary question will be whether Hetero’s final, FDA-approved label instructs users to perform every step of the claimed method. If Hetero successfully "carves out" the patented method of use from its label, it could present a defense to inducement.

V. Key Claim Terms for Construction

  • The Term: "induction phase" and "maintenance phase"

    • Context and Importance: These terms define the fundamental two-part structure of the claimed method. Their construction will determine what sequence and combination of administrative acts fall within the scope of the claim. Practitioners may focus on these terms because the infringement allegation relies on the COSELA® clinical study protocol, which delineates specific induction and maintenance cycles, potentially creating arguments about whether the claim terms are limited to that specific structure.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claim language itself describes the phases functionally: the induction phase involves the three-part combination therapy, while the maintenance phase involves administering the checkpoint inhibitor after the induction phase ceases. This functional definition may support a construction not strictly limited to a certain number of cycles (’352 Patent, col. 5:65-6:10).
      • Evidence for a Narrower Interpretation: The patent’s detailed description and figures describe specific embodiments with a set number of induction cycles (e.g., "up to 4 cycles") followed by a maintenance phase. A defendant may argue this context narrows the terms to regimens that closely mirror these examples (’352 Patent, FIG. 41; col. 30:50-54).

  • The Term: "chemotherapeutic agent is cytotoxic to immune effector cells"

    • Context and Importance: This limitation defines a required characteristic of the co-administered chemotherapy. The infringement case rests on the premise that the standard-of-care chemotherapies used with trilaciclib possess this property.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent’s background section broadly states that "chemotherapy itself can cause damage to various cell types of the immune system," suggesting this is a well-understood and general property of the class of agents, not a narrow technical requirement requiring a specific threshold of cytotoxicity (’352 Patent, col. 1:11-13).
      • Evidence for a Narrower Interpretation: A defendant could argue this term requires a specific, heightened level of cytotoxicity that is not met by all chemotherapeutic agents under all conditions, potentially raising a factual dispute about whether agents like carboplatin and etoposide always meet this definition in the context of the accused regimen.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement of infringement of the ’352 patent. The basis for this allegation is that Hetero’s ANDA Product Labeling, by being substantially identical to the COSELA® label, will necessarily instruct physicians to administer the drug in a manner that directly infringes the method claims (Compl. ¶75-77). The complaint also pleads contributory infringement, alleging that Hetero's product is especially made for infringing use and is not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶78).
  • Willful Infringement: The complaint alleges that Hetero has acted with full knowledge of the patents-in-suit, stemming from its Paragraph IV certification, and without a reasonable basis for believing it would not be liable for infringement (Compl. ¶81, ¶92). This alleged knowledge, combined with the act of filing the ANDA, forms the basis for the willfulness claim.

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

  • A core issue will be one of induced infringement: does Hetero's final, FDA-approved product label contain instructions that will inevitably lead physicians to practice every limitation of the asserted method claim of the ’352 patent? The outcome may depend on whether Hetero can successfully "carve out" the patented method of use from its label.
  • A key question for the ’666 patent will be one of composition: does Hetero's ANDA product, as manufactured, contain the specific crystalline morphic form of trilaciclib claimed in the ’666 patent? This will be a purely technical and evidentiary question requiring detailed product analysis.
  • A central validity question, though not detailed in the complaint, will likely be obviousness: can a defendant demonstrate with clear and convincing evidence that combining a known CDK4/6 inhibitor with a known chemo-immunotherapy regimen according to the claimed timing protocol would have been obvious to a person of ordinary skill in the art to achieve the claimed benefits?