DCT

1:23-cv-06667

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: 1:23-cv-06667, D.N.J., 08/21/2023
  • Venue Allegations: Plaintiffs allege venue is proper in the District of New Jersey because various U.S.-based defendants maintain a regular and established place of business in the district, and foreign-based defendants are subject to personal jurisdiction there. The complaint further alleges that the defendants committed acts of infringement in the district by preparing or assisting in the preparation of their Abbreviated New Drug Applications (ANDAs).
  • Core Dispute: Plaintiffs allege that Defendants' filing of ANDAs to seek FDA approval for generic versions of the COPD drug YUPELRI® (revefenacin) constitutes an act of infringement of a patent covering specific crystalline forms of the drug's active ingredient.
  • Technical Context: The technology concerns novel crystalline forms (polymorphs) of revefenacin, a long-acting muscarinic antagonist used to treat chronic obstructive pulmonary disease (COPD), designed to have improved physical properties for pharmaceutical manufacturing and delivery via inhalation.
  • Key Procedural History: This is a Hatch-Waxman action filed in response to multiple defendants submitting ANDAs with Paragraph IV certifications, asserting that U.S. Patent No. 11,691,948 is invalid, unenforceable, or will not be infringed by their proposed generic products. The complaint notes that the patent-in-suit was issued on July 4, 2023, and listed in the FDA's Orange Book on July 5, 2023. Plaintiffs also reference prior, consolidated litigation (1:23-cv-00926) against the same defendants concerning other patents related to YUPELRI®.

Case Timeline

Date Event
2009-07-15 ’948 Patent Priority Date
2023-01-05 Teva sends initial notice letter regarding its ANDA
2023-01-09 Eugia sends initial notice letter regarding its ANDA
2023-07-04 U.S. Patent No. 11,691,948 issues
2023-07-05 ’948 Patent listed in the FDA Orange Book for YUPELRI®
2023-07-31 Eugia sends second notice letter with Paragraph IV certification for the ’948 Patent
2023-08-21 Complaint Filed

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

U.S. Patent No. 11,691,948 - “Crystalline Freebase Forms of a Biphenyl Compound”

  • Patent Identification: U.S. Patent No. 11,691,948, issued July 4, 2023. (Compl. ¶145).

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of developing pharmaceutical agents for inhalation. For a drug to be manufactured effectively into a dry powder or nebulizer formulation, it is "highly desirable to have a crystalline form... that is neither hygroscopic nor deliquescent and which has a relatively high melting point," allowing it to be micronized into fine particles without decomposing. (’948 Patent, col. 1:37-42).
  • The Patented Solution: The invention provides novel crystalline forms of the active ingredient revefenacin, designated as Form III and Form IV. These specific solid-state forms are described as having "different and particularly useful properties, including higher melting points" compared to previously known forms, making them more suitable for pharmaceutical development. (’948 Patent, col. 1:45-49, Abstract). The forms are defined by their unique powder x-ray diffraction (PXRD) patterns, which serve as structural fingerprints. (’948 Patent, col. 2:50-65).
  • Technical Importance: By providing stable, high-melting-point crystalline forms, the invention enables the reliable manufacturing of revefenacin into consistent, fine-particle formulations required for effective delivery to the lungs for treating COPD. (’948 Patent, col. 4:40-50).

Key Claims at a Glance

The complaint alleges infringement of "one or more claims" without specifying which ones (Compl. ¶269). Independent claim 4 is representative of the core composition-of-matter invention.

  • Independent Claim 4:
    • A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester (revefenacin).
    • The crystalline freebase is characterized by a powder x-ray diffraction pattern with peaks at specific 2θ values (6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.1).
    • The crystalline freebase is further characterized by having five or more additional peaks from a specified list.
    • The crystalline freebase is dissolved in a solvent and then combined with the carrier.
    • The final pharmaceutical composition has a pH of about 5.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are the proposed generic versions of YUPELRI® (revefenacin) inhalation solution, for which the defendants have filed ANDAs with the FDA (e.g., Eugia ANDA No. 218128, Mankind ANDA No. 218089, Teva ANDA No. 217015). (Compl. ¶1).

Functionality and Market Context

  • The defendants' ANDA products are intended to be generic equivalents of YUPELRI®, a prescription medicine administered via a jet nebulizer for the "maintenance treatment of patients with chronic obstructive pulmonary disease ('COPD')." (Compl. ¶149, 165).
  • The complaint alleges that the active ingredient in the defendants' products is revefenacin, the same as in YUPELRI®, and that the defendants' ANDAs assert that their products are bioequivalent to YUPELRI®. (Compl. ¶162, 163). This litigation under the Hatch-Waxman Act is the statutory mechanism for resolving patent disputes before a generic drug enters the market. (Compl. ¶1).

IV. Analysis of Infringement Allegations

The complaint makes general allegations of infringement without providing detailed factual support or a claim chart. The following table summarizes the infringement theory based on the complaint's narrative allegations against the representative independent claim 4. No probative visual evidence provided in complaint.

’948 Patent Infringement Allegations

Claim Element (from Independent Claim 4) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a crystalline freebase of [revefenacin] The defendants' ANDA Products are pharmaceutical compositions that allegedly contain revefenacin, which is the "same active ingredient used in the compositions described and claimed" in the patent. ¶162 col. 2:50-58
characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.1 The complaint does not present PXRD data but implicitly alleges that the defendants' revefenacin meets this limitation by stating it is the "same active ingredient used in the compositions... claimed" in the patent. ¶162 col. 2:58-62
and further characterized by having five or more additional diffraction peaks at 2θ values selected from [a specified list] As with the primary peaks, the complaint makes a general allegation that the active ingredient is the one claimed in the patent, which would necessarily include this characteristic. ¶162 col. 2:62-3:2
and wherein the crystalline freebase is dissolved in a solvent and then combined with the pharmaceutically acceptable carrier The defendants' ANDA Products are described as an "inhalation solution," which the complaint alleges infringes claims covering compositions where the crystalline freebase is dissolved. ¶1, ¶162 col. 12:15-24
and wherein the pharmaceutical composition has a pH of about 5 The complaint does not provide a specific allegation regarding the pH of the defendants' products but alleges they are bioequivalent to YUPELRI®, which the patent teaches can be formulated to a pH of about 5. ¶163 col. 3:30-35

Identified Points of Contention

  • Scope Questions: The central issue is whether the revefenacin in the defendants' ANDA products is, in fact, the specific "crystalline freebase" (Form III or IV) claimed in the patent. The complaint's reliance on the "same active ingredient" allegation raises the question of whether defendants might use a different, non-infringing polymorph or an amorphous form of revefenacin.
  • Technical Questions: What evidence demonstrates that the defendants' manufacturing process or final product meets the claim limitations related to the PXRD peaks and the final solution pH? The complaint makes conclusory allegations of infringement without providing any analytical data (e.g., PXRD scans, pH measurements) for the accused products, which will be a primary focus of discovery and expert testimony. Further, a question arises as to how a claim reciting a crystalline solid is infringed by a final product that is a solution.

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: The definition of the patented crystalline structure is the cornerstone of the infringement case. The entire dispute hinges on whether the defendants' active pharmaceutical ingredient falls within the scope of this term. The defendants will likely seek to distinguish their product's physical form or challenge the validity of the claim over other known forms.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: Plaintiffs may argue that the use of "comprising" and the "±0.1" tolerance for peak positions indicate that the claim is not limited to an exact replica of the examples, but covers any crystalline form that substantially embodies the claimed PXRD fingerprint. (’948 Patent, col. 2:58-62).
    • Evidence for a Narrower Interpretation: Defendants may argue that the term should be limited to the specific polymorphs (Form III or Form IV) detailed in the specification's examples and figures. They could point to the detailed characterization data, including relative peak intensities and DSC thermograms, as context that narrows the meaning to just those specific forms. (’948 Patent, Fig. 1, Fig. 4, Example 1).

  • The Term: "dissolved in a solvent"

  • Context and Importance: This process-like limitation in a composition claim (e.g., Claim 4) is critical because the final accused product is a solution, not a solid. Practitioners may focus on this term to dispute whether infringement is determined by the starting materials or the final product's characteristics.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: Plaintiffs may argue that this term simply describes the necessary step to create the claimed "pharmaceutical composition" that is a solution, and that any generic revefenacin solution for inhalation must inherently be made by dissolving the active ingredient. (’948 Patent, col. 12:15-24).
    • Evidence for a Narrower Interpretation: Defendants could argue this is a strict process limitation that they do not meet if, for example, they use a different manufacturing technique that does not start with the claimed crystalline freebase. They may also raise the question of whether this limitation, describing an action rather than a structure, renders the composition claim indefinite.

VI. Other Allegations

  • Indirect Infringement: The complaint does not contain specific factual allegations supporting indirect infringement but includes prayers for relief seeking to enjoin defendants from "actively inducing or contributing to the infringement." (Compl. Prayer for Relief ¶(f), (q)). Such a claim would likely be based on the defendants' proposed product labeling instructing end-users on how to use the allegedly infringing product after it is approved.
  • Willful Infringement: The complaint alleges that infringement "has been, and continues to be, deliberate." (Compl. ¶273, 281, etc.). This allegation is based on the defendants having knowledge of the ’948 Patent, as evidenced by their sending of Paragraph IV certification notice letters to the plaintiffs. (Compl. ¶166, 184, etc.).

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

  • A central evidentiary question will be one of physical identity: What is the precise solid-state form of the revefenacin active ingredient used and produced by the defendants? The case will likely turn on competing crystallographic analyses to determine if the accused products meet the specific PXRD fingerprints required by the patent claims.
  • A key legal question will be one of claim scope: How will the court construe composition claims that include process-like limitations, such as requiring a specific "crystalline freebase" that is subsequently "dissolved" to form the final product? The interpretation of these limitations will be critical in determining whether an infringement can occur when the final accused product is a solution, not the claimed solid.
  • A third core issue will be one of proof: Can Plaintiffs meet their burden of proof given the complaint's current lack of specific factual evidence, such as PXRD data, demonstrating that the accused generic products contain the patented crystalline form? The outcome may depend heavily on facts developed during discovery.