DCT

1:23-cv-00187

Theravance Biopharma R&D IP LLC v. Lupin Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00187, D. Del., 02/17/2023
  • Venue Allegations: Venue is alleged to be proper as Defendants Lupin Inc. and Lupin Pharmaceuticals are incorporated in Delaware, and Lupin Ltd. is a foreign corporation subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiffs allege that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the YUPELRI® inhalation solution constitutes an act of infringement of five patents related to the compound revefenacin, its crystalline forms, and its methods of use for treating Chronic Obstructive Pulmonary Disease (COPD).
  • Technical Context: The technology concerns specific crystalline forms of a pharmaceutical compound (revefenacin) and methods for its use in treating COPD, particularly in patient subgroups with specific respiratory characteristics.
  • Key Procedural History: This Hatch-Waxman litigation was initiated within 45 days of Plaintiffs’ receipt of Defendants’ January 5, 2023 notice letter, which contained a Paragraph IV certification asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed by the proposed generic product.

Case Timeline

Date Event
2009-07-15 Priority Date for ’451, ’028, ’081, ’289 Patents
2013-09-24 U.S. Patent No. 8,541,451 Issues
2017-09-19 U.S. Patent No. 9,765,028 Issues
2018-08-30 Priority Date for ’531 Patent
2020-02-04 U.S. Patent No. 10,550,081 Issues
2021-05-18 U.S. Patent No. 11,008,289 Issues
2022-11-01 U.S. Patent No. 11,484,531 Issues
2023-01-05 Lupin Notice Letter Sent
2023-02-17 Complaint Filed

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

U.S. Patent No. 8,541,451 - “Crystalline Freebase Forms of a Biphenyl Compound”

The Invention Explained

  • Problem Addressed: For therapeutic agents delivered by inhalation, it is technically advantageous to have a crystalline form that is not hygroscopic (does not readily absorb moisture) and has a high melting point, which allows the material to be micronized into fine particles without significant decomposition (’289 Patent, col. 2:39-44).
  • The Patented Solution: The invention provides novel crystalline freebase forms of the biphenyl compound known as revefenacin. The specification describes specific polymorphs, designated as Form III and Form IV, which are characterized by distinct powder x-ray diffraction (PXRD) patterns and are stated to have useful properties, including higher melting points than previously known forms (’289 Patent, Abstract; col. 2:44-48).
  • Technical Importance: The specific crystalline structure of an active pharmaceutical ingredient can significantly impact its stability, manufacturability, and bioavailability, making the discovery of stable, well-characterized polymorphs critical for developing a consistent and effective inhaled drug product (’289 Patent, col. 2:39-44).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims of the ’451 patent but does not identify any specific claims asserted (Compl. ¶80-81).

U.S. Patent No. 9,765,028 - “Crystalline Freebase Forms of a Biphenyl Compound”

The Invention Explained

  • Problem Addressed: As with the related ’451 patent, this patent addresses the need for stable crystalline forms of a therapeutic compound suitable for formulation and delivery via inhalation devices (’289 Patent, col. 2:39-44).
  • The Patented Solution: The invention, which shares a specification with the ’451 patent, discloses and claims specific crystalline polymorphs of revefenacin, including forms identified as Form III and Form IV, which possess distinct physical properties such as unique PXRD patterns and thermal characteristics (’289 Patent, Abstract; col. 2:44-48).
  • Technical Importance: The identification of these specific crystalline forms provides a basis for developing a reproducible manufacturing process and a stable pharmaceutical composition for treating pulmonary disorders like COPD (’289 Patent, col. 2:39-44).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims of the ’028 patent but does not identify any specific claims asserted (Compl. ¶88-89).

U.S. Patent No. 10,550,081 - “Crystalline Freebase Forms of a Biphenyl Compound”

Technology Synopsis

The ’081 patent arises from the same family as the ’451 and ’028 patents and is directed to the same core technology: novel crystalline freebase forms of revefenacin, a compound useful for treating pulmonary disorders. The patent describes specific polymorphs with properties suitable for pharmaceutical development, particularly for inhaled therapies (’081 Patent, Abstract; col. 2:39-44).

Asserted Claims

The complaint alleges infringement of one or more claims without specifying them (Compl. ¶95-96).

Accused Features

The accused features are the processes used to prepare Lupin’s ANDA product and the resulting product itself, which allegedly contains revefenacin in a patented crystalline form (Compl. ¶66, 74).

U.S. Patent No. 11,008,289 - “Crystalline Freebase Forms of a Biphenyl Compound”

Technology Synopsis

Continuing the same inventive line as the patents above, the ’289 patent discloses and claims specific crystalline freebase forms of revefenacin. It identifies polymorphs (Form III and Form IV) with distinct and advantageous physical characteristics, such as higher melting points, that are important for creating stable and effective inhaled pharmaceutical products (’289 Patent, Abstract; col. 2:39-44).

Asserted Claims

The complaint alleges infringement of one or more claims without specifying them (Compl. ¶102-103).

Accused Features

Infringement is alleged based on Lupin’s proposed generic revefenacin product, which is alleged to be or to contain one of the claimed crystalline forms (Compl. ¶66, 74).

U.S. Patent No. 11,484,531 - “Methods for Treating Chronic Obstructive Pulmonary Disease”

Technology Synopsis

This patent addresses the problem that COPD patients with low peak inspiratory flow rate (PIFR) may not be able to use dry powder inhalers effectively. The patented solution is a method of treatment that involves first selecting a specific sub-population of COPD patients—those with both a PIFR less than about 60 L/min and a percent predicted forced expiratory volume in one second (FEV1) less than about 50 percent—and then administering a specific dose of revefenacin to that patient using a nebulizer (’531 Patent, Abstract; Compl. ¶113).

Asserted Claims

The complaint asserts independent claim 1 (Compl. ¶113).

Accused Features

The accused features are the acts of using Lupin's proposed generic product in accordance with its proposed labeling, which Plaintiffs allege will instruct and encourage healthcare providers to perform the patented method of selecting and treating the specified patient population (Compl. ¶111-112, 117).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendants' proposed generic version of YUPELRI® (revefenacin) inhalation solution, which is the subject of ANDA No. 218088 (the "Lupin ANDA Product") (Compl. ¶1, 16).

Functionality and Market Context

  • The Lupin ANDA Product contains the active ingredient revefenacin, a long-acting muscarinic antagonist, and is intended for the maintenance treatment of patients with COPD (Compl. ¶49, 66, 69). The complaint alleges that the product is administered once daily via a nebulizer (Compl. ¶49).
  • Defendants assert in their ANDA that the Lupin ANDA Product is bioequivalent to YUPELRI® and are seeking approval for the same indication (Compl. ¶67-68).

IV. Analysis of Infringement Allegations

U.S. Patent No. 8,541,451 Infringement Allegations

The complaint does not provide a claim chart or identify specific asserted claims for the ’451 patent. The infringement theory is based on Lupin’s submission of an ANDA for a product containing revefenacin, the same active ingredient described in the patent (Compl. ¶66). The filing of the ANDA is alleged to be a technical act of infringement under 35 U.S.C. § 271(e)(2)(A), and the future commercial manufacture and sale of the product is alleged to constitute infringement under 35 U.S.C. § 271(a) (Compl. ¶80-81).

  • Identified Points of Contention:
    • Technical Questions: A central technical question will be whether the revefenacin in Lupin's ANDA Product actually exists in a crystalline form that meets the specific diffraction peak limitations and other physical characteristics required by the asserted claims of the ’451 patent. The complaint does not provide specific evidence on the crystalline form of Lupin's product.

U.S. Patent No. 9,765,028 Infringement Allegations

The complaint does not provide a claim chart or identify specific asserted claims for the ’028 patent. The infringement theory mirrors that for the ’451 patent, alleging that Lupin’s ANDA filing and its proposed future commercial activities for its generic revefenacin product will infringe one or more claims of the ’028 patent, which covers specific crystalline forms of that compound (Compl. ¶88-89).

  • Identified Points of Contention:
    • Technical Questions: As with the ’451 patent, the core of the dispute will likely involve factual questions of proof. What evidence demonstrates that the process used to manufacture Lupin's product results in, or that the final product itself contains, a crystalline form of revefenacin falling within the scope of the asserted claims of the ’028 patent?

No probative visual evidence provided in complaint.

V. Key Claim Terms for Construction

The complaint does not identify specific asserted claims for the ’451 patent or the ’028 patent, precluding an analysis of key claim terms for construction at this stage.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon approval, Lupin will actively induce infringement of the ’531 patent (Compl. ¶110). This allegation is based on the assertion that Lupin’s FDA-approved package insert will direct and encourage healthcare providers and patients to perform the patented method of selecting specific COPD patients and administering the Lupin ANDA product with a nebulizer (Compl. ¶111-112, 117). The complaint also makes general allegations of inducement and contributory infringement for all patents-in-suit (Compl. ¶71, 73).
  • Willful Infringement: The complaint alleges that Lupin had knowledge of all five patents-in-suit when it submitted its ANDA (Compl. ¶70, 84, 91, 98, 105). It further alleges that Lupin’s infringement "has been, and continues to be, deliberate," which may form the basis for a claim of willful infringement (Compl. ¶84, 91, 98, 105).

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

  • A central issue for the four composition of matter patents (’451, ’028, ’081, ’289) will be one of evidentiary proof: what evidence will establish that the active ingredient in Defendants' proposed generic product is, in fact, the specific crystalline polymorph required by the patent claims?
  • For the method-of-use patent (’531), a key legal and factual question will be one of induced infringement: does the language of Defendants’ proposed product label specifically encourage, recommend, or promote the performance of all steps of the claimed method, including the crucial step of selecting patients based on the dual criteria of low PIFR and low percent predicted FEV1?
  • A cross-cutting issue will be one of claim scope: for the composition patents, the litigation may focus on the interpretation of the claim language defining the polymorphs by their PXRD peaks (e.g., the significance of the "±0.1" notation), and for the method patent, on the construction of terms like "about 60 L/min" and "about 50 percent."