DCT

1:24-cv-00150

Theravance Biopharma R&D IP LLC v. Eugia Pharma Specialities Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00150, D.N.J., 01/09/2024
  • Venue Allegations: Venue is alleged based on the U.S. Defendants having regular and established places of business in New Jersey, and for the foreign Defendants, on the basis that they are subject to personal jurisdiction in the district and have litigated prior related cases in the District of New Jersey without contesting venue.
  • Core Dispute: Plaintiffs allege that Defendants' submission of Abbreviated New Drug Applications (ANDAs) seeking FDA approval to market generic versions of the COPD drug YUPELRI® constitutes an act of infringement of a patent directed to specific crystalline forms of the active ingredient, revefenacin.
  • Technical Context: The technology concerns pharmaceutical polymorphism, specifically identifying stable crystalline structures of an active pharmaceutical ingredient, which is critical for ensuring consistent manufacturing, stability, and performance of a drug product, particularly for inhaled therapies.
  • Key Procedural History: This action is a follow-on suit to prior litigations between the parties concerning other patents listed in the FDA's Orange Book for YUPELRI®. The patent-in-suit was recently issued, and this complaint asserts it against the same ANDA filers involved in the consolidated prior actions. The complaint notes that Defendants have previously appeared in the District of New Jersey in related Hatch-Waxman cases and did not contest jurisdiction or venue.

Case Timeline

Date Event
2009-07-15 ’898 Patent Priority Date
2023-01-05 Mankind and Lupin Notice Letter Date
2023-01-09 Eugia Notice Letter Date
2023-01-13 Orbicular Notice Letter Date
2023-01-17 Cipla Notice Letter Date
2024-01-02 ’898 Patent Issue Date
2024-01-09 Complaint Filing Date

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

U.S. Patent No. 11,858,898, “Crystalline Freebase Forms of a Biphenyl Compound,” issued January 2, 2024

The Invention Explained

  • Problem Addressed: The patent addresses the need for a crystalline form of the active pharmaceutical ingredient revefenacin that possesses desirable physical properties for use in inhalation therapies. Specifically, it seeks a form that is not hygroscopic (does not readily absorb moisture) and has a high melting point, which allows the material to be processed into fine particles (micronized) for inhalation without significant decomposition (’898 Patent, col. 1:35-42).
  • The Patented Solution: The invention discloses new crystalline polymorphs of revefenacin, designated as Form III and Form IV. These novel forms are distinguished from prior art forms and from each other by their unique physical characteristics, most notably their powder X-ray diffraction (PXRD) patterns and thermal properties as measured by differential scanning calorimetry (DSC) (’898 Patent, Abstract; col. 1:42-49). The patent asserts these new forms possess useful properties, including higher melting points than previously known forms (’898 Patent, col. 1:45-46).
  • Technical Importance: For inhaled drugs, the physical form of the active ingredient is critical, as it impacts the drug's stability during storage, its manufacturability, and its aerodynamic performance upon administration, all of which are essential for consistent and effective therapy (’898 Patent, col. 1:30-35).

Key Claims at a Glance

  • The complaint asserts "one or more claims" of the ’898 patent (Compl. ¶192). Representative independent claims include:
    • Claim 1 (Method of Treatment): A method of treating chronic obstructive pulmonary disease (COPD) in a human patient by administering a pharmaceutical composition containing a crystalline freebase of revefenacin, where the crystalline freebase is characterized by a PXRD pattern with diffraction peaks at 2θ values of 6.6±0.1 and 20.2±0.1.
    • Claim 9 (Composition of Matter): A crystalline form of revefenacin characterized by a PXRD pattern with diffraction peaks at 2θ values of 11.4±0.1 and 11.6±0.1.
  • The complaint does not specify other claims but implicitly reserves the right to assert them.

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are the generic revefenacin inhalation solutions for which Defendants seek FDA approval via ANDA No. 218128 (Eugia), ANDA No. 218089 (Mankind), ANDA No. 218088 (Lupin), ANDA No. 217868 (Orbicular), and ANDA No. 217958 (Cipla) (Compl. ¶1).

Functionality and Market Context

The Defendants' ANDA products are proposed generic versions of Plaintiffs' YUPELRI® product (Compl. ¶¶ 20, 25, 32, 35, 40). The complaint alleges that the active ingredient in these products is revefenacin and that the products are intended for the same indication as YUPELRI®: the maintenance treatment of patients with COPD (Compl. ¶¶ 120, 123, 135, 138). The complaint further alleges that Defendants' ANDAs assert that their products are bioequivalent to YUPELRI® (Compl. ¶¶ 121, 136, 151, 168, 183).

IV. Analysis of Infringement Allegations

The complaint alleges infringement under 35 U.S.C. § 271(e)(2)(A), where the filing of an ANDA to market a drug claimed in a patent before its expiration is a statutory act of infringement. The core allegation is that the products described in the Defendants' ANDAs, if manufactured and sold, would infringe the ’898 patent. Figure 1 of the patent, attached as Exhibit A to the complaint, provides a powder X-ray diffraction (PXRD) pattern alleged to characterize the novel crystalline Form III of revefenacin (Compl., Ex. A, FIG. 1).

’898 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating chronic obstructive pulmonary disease in a human patient, the method comprising: administering a pharmaceutical composition... Defendants' ANDAs seek approval to market their products for the maintenance treatment of patients with COPD, which is the indication on the YUPELRI® label. ¶123 col. 32:46-50
...comprising a pharmaceutically acceptable carrier and a crystalline freebase of biphenyl-2-ylcarbamic acid... The active ingredient in the accused ANDA products is alleged to be revefenacin, the same active ingredient described and claimed in the patent. ¶120 col. 32:57-63
...wherein the crystalline freebase is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 20 values of 6.6±0.1 and 20.2±0.1. The complaint alleges that the active ingredient in the accused products is the same as that used in the claimed compositions, but provides no direct evidence, such as a PXRD pattern, that Defendants' API meets this specific structural limitation. ¶120 col. 32:63-65

Identified Points of Contention

  • Technical Question: The central factual dispute will be whether the revefenacin API used by each Defendant possesses the specific crystalline structure defined by the patent's claims. What evidence does each Defendant's ANDA contain regarding the polymorphic form of its revefenacin, and does that form exhibit the PXRD peaks or thermal properties required by claims such as claims 1, 9, or 12? The complaint's allegations on this point are inferential, making this a primary focus for discovery.
  • Scope Questions: The interpretation of the term "comprising" in the claims will be significant. A key question for the court may be whether the presence of the recited PXRD peaks is sufficient for a finding of infringement, or whether a Defendant could argue non-infringement by showing that the overall pattern of its API is different from the Form III or Form IV disclosed in the patent, despite the presence of some overlapping peaks.

V. Key Claim Terms for Construction

  • The Term: "crystalline freebase ... characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of..."
  • Context and Importance: This phrase is the core of the patent's composition and method claims, defining the invention by its specific physical structure. The construction of this term, particularly the word "comprising" and the significance of the recited peaks relative to the full PXRD pattern, will be dispositive for infringement. Practitioners may focus on this term because proof of infringement depends entirely on matching the Defendants' API to this definition.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The use of the open-ended term "comprising" suggests that the presence of the listed peaks is sufficient for infringement, regardless of whether other, unlisted peaks are also present ('898 Patent, col. 32:65). Plaintiffs may argue this means the claim is met so long as the required peaks are found in the accused product's PXRD pattern.
    • Evidence for a Narrower Interpretation: The specification repeatedly describes the new forms by referencing the figures, for example, stating that Form III is "characterized by a PXRD pattern in which the peak positions are substantially in accordance with those shown in FIG. 1" ('898 Patent, col. 8:25-28). Defendants may argue that this language requires a holistic comparison to the entire pattern in the figure, not just the presence of a few enumerated peaks, to meet the "characterized by" limitation.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement of infringement of method claims. The alleged factual basis is that Defendants' ANDA products will be sold with proposed labeling that instructs healthcare providers and patients to administer the drug for the treatment of COPD, thereby directing them to perform the patented method (Compl. ¶¶ 125, 127).
  • Willful Infringement: The complaint alleges that Defendants have actual knowledge of the ’898 patent, at least as of the filing of the lawsuit, and that their infringement "has been, and continues to be, deliberate" (Compl. ¶¶ 124, 195). This forms the basis for a claim of post-suit willfulness.

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

  • A central evidentiary question will be one of structural identity: What is the precise polymorphic form of the revefenacin API within each Defendant’s proposed generic product? Discovery and subsequent expert analysis of experimental data, particularly PXRD and DSC data, will be required to determine if the Defendants’ materials fall within the structural definitions of the asserted claims.
  • A key legal question will be one of definitional scope: How will the court construe the phrase "characterized by a powder x-ray diffraction pattern comprising..."? The outcome will likely turn on whether infringement requires only the presence of the enumerated peaks, or a more holistic similarity to the full diffraction patterns disclosed in the patent's specification and figures.