DCT

3:25-cv-00578

Astellas Pharma Inc v. Hikma Pharma USA Inc

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:25-cv-00578, D.N.J., 01/16/2025
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because the defendant, Hikma, maintains a regular and established place of business in the state, is registered with state agencies, employs personnel in New Jersey, and has previously submitted to the court's jurisdiction in other matters.
  • Core Dispute: Plaintiffs allege that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market generic versions of the prostate cancer drug Xtandi® infringes patents related to a specific drug formulation and a method of combination therapy.
  • Technical Context: The technology concerns pharmaceutical formulations designed to improve the delivery and efficacy of enzalutamide, an androgen receptor inhibitor used for treating various forms of prostate cancer.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following a notice letter from Hikma, dated December 6, 2024, advising of its ANDA filing and asserting that claims of the '689 patent were invalid, unenforceable, or not infringed. Plaintiffs filed this suit within the 45-day statutory window. The complaint also notes related, pending litigation against other generic pharmaceutical manufacturers concerning the same drug product.

Case Timeline

Date Event
2012-09-11 Priority Date for U.S. Patent No. 11,839,689
2015-08-12 Priority Date for U.S. Patent No. 12,161,628
2020-08-04 FDA approves NDA for Xtandi® tablets (40 mg and 80 mg)
2023-11-16 FDA approves expanded indication for Xtandi® tablets
2023-12-12 U.S. Patent No. 11,839,689 issues
2024-12-06 Hikma sends notice letter to Plaintiffs regarding ANDA filing
2024-12-10 U.S. Patent No. 12,161,628 issues
2025-01-03 Hikma notified of the '628 patent
2025-01-16 Complaint filed

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

U.S. Patent No. 11,839,689 - FORMULATIONS OF ENZALUTAMIDE, issued December 12, 2023

The Invention Explained

  • Problem Addressed: The patent's background section explains that while enzalutamide is an effective agent for treating prostate cancer, its crystalline form has low aqueous solubility, which can limit its absorption by the body and overall bioavailability ('689 Patent, col. 1:15-18; col. 2:46-52).
  • The Patented Solution: The invention claims to solve this problem by creating a "solid dispersion" where enzalutamide is in an amorphous (non-crystalline) state, mixed with a "concentration-enhancing polymer" such as hydroxypropyl methylcellulose acetate succinate (HPMCAS) ('689 Patent, col. 1:25-31). This amorphous formulation is designed to dissolve more quickly and to a greater extent than the crystalline form, thereby improving the drug's solubility and absorption ('689 Patent, col. 1:46-52). The patent's Figure 1 visually contrasts the X-ray diffraction patterns of the amorphous dispersion against the bulk crystalline drug, showing the absence of sharp peaks characteristic of a crystalline structure.
  • Technical Importance: Developing formulations that improve the oral bioavailability of poorly soluble drugs is a critical and persistent challenge in the pharmaceutical industry, as it allows for more effective and reliable oral dosing.

Key Claims at a Glance

  • The complaint asserts infringement of at least Claim 1 ('689 Patent, col. 49:23-26).
  • Independent Claim 1 requires:
    • A pharmaceutical composition
    • comprising a solid dispersion
    • consisting essentially of amorphous enzalutamide
    • and hydroxypropyl methylcellulose acetate succinate (HPMCAS).
  • The complaint notes that dependent claims specify the formulation is a tablet and reserves the right to assert them (Compl. ¶41).

U.S. Patent No. 12,161,628 - COMBINATION THERAPY, issued December 10, 2024

The Invention Explained

  • Problem Addressed: The patent explains that enzalutamide is metabolized by certain enzymes in the body, particularly CYP3A4 ('628 Patent, col. 1:60-62). When enzalutamide is co-administered with a drug that is a "strong CYP3A4 inducer" (such as the antibiotic rifampin), the metabolism of enzalutamide is accelerated, leading to a significant decrease in its plasma concentration and potentially compromising its therapeutic effect ('628 Patent, col. 2:1-6).
  • The Patented Solution: The invention provides a specific method-of-use to counteract this drug-drug interaction. It discloses that increasing the daily dose of enzalutamide to 240 mg when co-administered with a strong CYP3A4 inducer can compensate for the increased metabolism, thereby maintaining a therapeutically effective concentration of the drug ('628 Patent, col. 2:7-13).
  • Technical Importance: Managing drug-drug interactions is crucial for patient safety and treatment efficacy, and this invention provides a specific dosing regimen to address a clinically significant interaction.

Key Claims at a Glance

  • The complaint asserts infringement of at least Claim 1 ('628 Patent, col. 14:8-11).
  • Independent Claim 1 requires:
    • A method of treating prostate cancer
    • in a patient to whom rifampin is administered
    • comprising co-administering to the patient a daily dose of 240 mg of enzalutamide.

III. The Accused Instrumentality

Product Identification

The accused products are Hikma's generic enzalutamide tablets in 40 mg and 80 mg dosages, for which Hikma seeks FDA approval via ANDA No. 218731 (Compl. ¶29).

Functionality and Market Context

The complaint alleges that Hikma's generic products are generic versions of Plaintiffs' Xtandi® tablets and are intended for the same therapeutic uses (Compl. ¶¶30-31). The complaint asserts these products will be used for the treatment of castration-resistant prostate cancer, metastatic castration-sensitive prostate cancer, and non-metastatic castration-sensitive prostate cancer (Compl. ¶31). The complaint includes a chemical structure diagram of enzalutamide, the active pharmaceutical ingredient in both the brand-name and accused generic products (Compl. ¶18).

IV. Analysis of Infringement Allegations

'11,839,689 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
a pharmaceutical composition comprising a solid dispersion Hikma's generic products are alleged to contain a pharmaceutical composition comprising a solid dispersion. ¶46 col. 2:36-41
consisting essentially of amorphous enzalutamide The solid dispersion in Hikma's product is alleged to consist essentially of amorphous enzalutamide. ¶46 col. 1:46-52
and hydroxypropyl methylcellulose acetate succinate” (“HPMCAS”) The solid dispersion in Hikma's product is alleged to contain HPMCAS. ¶46 col. 12:30-34

Identified Points of Contention

  • Scope Questions: The infringement analysis for the '689 patent may focus on the term "consisting essentially of." A primary question will be factual and legal: does Hikma's proposed formulation contain any unlisted components that materially affect the basic and novel properties (i.e., enhanced solubility and dissolution stability) of the claimed amorphous solid dispersion? The complaint alleges Hikma "copied" the claimed invention, which suggests a theory of direct compositional overlap (Compl. ¶44).
  • Technical Questions: A key factual question will be the precise composition of Hikma's ANDA product. Discovery will be required to determine if the enzalutamide is in the required "amorphous" state and if the excipients are limited to those that do not materially alter the invention's properties.

'12,161,628 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating prostate cancer in a patient to whom rifampin is administered The proposed labeling for Hikma's generic product will allegedly direct its use for treating prostate cancer in patients who may also be receiving rifampin, a known CYP3A4 inducer. ¶59 col. 2:27-34
comprising co-administering to the patient a daily dose of 240 mg of enzalutamide. The proposed labeling will allegedly instruct the co-administration of Hikma's product at a specific dose of 240 mg per day for patients who are concurrently receiving rifampin. ¶59 col. 2:7-13

Identified Points of Contention

  • Scope Questions: The dispute over the '628 patent will likely center on the requirements for induced infringement. The central question for the court will be whether the language in Hikma's proposed product label actively encourages, recommends, or promotes the claimed method, thus demonstrating a specific intent to induce infringement by physicians and patients.
  • Technical Questions: An evidentiary question will be the exact wording of Hikma's proposed label. Does the label merely provide information about a potential drug interaction with rifampin, or does it affirmatively instruct physicians to administer the specific 240 mg dose claimed in the patent as the prescribed response to that interaction?

V. Key Claim Terms for Construction

The Term: "consisting essentially of" ('689 Patent, Claim 1)

Context and Importance

This transitional phrase is critical for defining the scope of the composition claim. Its construction will determine whether additional, unlisted excipients in Hikma's generic formulation fall outside the claim's boundaries, thereby avoiding infringement. Practitioners may focus on this term because it permits the presence of unlisted ingredients so long as they do not materially affect the "basic and novel properties" of the invention—here, the enhanced dissolution and bioavailability of amorphous enzalutamide.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The patent specification describes that other excipients, such as fillers, disintegrants, and lubricants, can be added to the composition to create final dosage forms like tablets ('689 Patent, col. 19:50-20:4; col. 25:35-40). This may support an interpretation that the presence of such conventional excipients does not materially alter the core properties of the solid dispersion itself.
  • Evidence for a Narrower Interpretation: A defendant could argue that any component that affects the stability of the amorphous form or the rate of dissolution would be a material alteration. The patent emphasizes the specific pairing of amorphous enzalutamide and a concentration-enhancing polymer as the core of the solution, which might support limiting the scope to exclude additives that interfere with that specific synergy ('689 Patent, col. 2:36-41).

The Term: "co-administering" ('628 Patent, Claim 1)

Context and Importance

This term defines the required relationship between the administration of enzalutamide and rifampin. Its construction is central to the inducement allegation, as Hikma's product label must be found to encourage the specific activity of "co-administering" the drugs.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The patent specification explicitly defines the term broadly, stating that "Co-administration does not require that both agents be administered in a single pharmaceutical composition, in the same dosage form, by the same route of administration, or for the same length of time" ('628 Patent, col. 2:19-24). It requires only that the "pharmacological effects" of the two agents overlap. This language provides strong support for a broad construction.
  • Evidence for a Narrower Interpretation: A defendant might attempt to argue for a more constrained temporal requirement, but the patent's express definition presents a significant challenge to such an argument. Any narrowing interpretation would likely have to arise from arguments related to the prosecution history, which is not available in the complaint.

VI. Other Allegations

Indirect Infringement

The complaint alleges that Hikma will induce infringement of the '628 patent. The basis for this allegation is that Hikma's proposed product labeling will instruct and encourage physicians and patients to perform the claimed method of use—specifically, to co-administer a 240 mg daily dose of enzalutamide to prostate cancer patients who are also taking rifampin (Compl. ¶¶58-59, 63).

Willful Infringement

The complaint alleges willful infringement of both patents. For the '689 patent, willfulness is based on Hikma's alleged knowledge of the patent from its Orange Book listing and the notice letter it sent (Compl. ¶48). For the '628 patent, willfulness is based on alleged knowledge since at least January 3, 2025, when Astellas notified Hikma of the patent (Compl. ¶¶54, 64). Plaintiffs also characterize the case as "exceptional," alleging Hikma's invalidity and non-infringement positions are devoid of an objective good faith basis (Compl. ¶50).

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

  • A central question for the '689 patent will be factual and definitional: Does Hikma's proposed generic formulation contain unlisted ingredients, and if so, does the evidence show that those ingredients "materially affect" the core solubility and stability properties of the claimed solid dispersion? The case may turn on the interpretation of "consisting essentially of" in the context of pharmaceutical formulation science.
  • A key issue for the '628 patent will be one of induced infringement: Will the final, approved FDA label for Hikma's product contain language that specifically instructs and encourages physicians to practice the claimed method—co-administering a 240 mg daily dose of enzalutamide to patients taking rifampin—thereby establishing Hikma's specific intent to induce infringement?