DCT

1:24-cv-01068

Astellas Pharma Inc v. Lupin Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-01068, D. Del., 09/24/2024
  • Venue Allegations: Plaintiff alleges venue is proper because one defendant is incorporated in Delaware, both defendants conduct continuous business in the district, and defendants have not challenged venue in prior related litigation in the same court.
  • Core Dispute: Plaintiff alleges that Defendant’s generic mirabegron extended-release tablets infringe a patent claiming methods of treating overactive bladder with a formulation that reduces the pharmacokinetic "food effect."
  • Technical Context: The technology concerns advanced pharmaceutical formulations designed to ensure consistent drug absorption and clinical effect for patients, irrespective of whether the medication is taken with or without food.
  • Key Procedural History: This action follows a series of litigations between the parties concerning the same generic product and other patents in the same family. The complaint notes that Lupin filed its Abbreviated New Drug Application (ANDA) and sent notice letters to Astellas in 2016 and 2021, received final FDA approval in 2022, and commercially launched its products in 2024. The patent-in-suit issued on the same day the complaint was filed.

Case Timeline

Date Event
2010-03-29 ’189 Patent Priority Date
2016-08-25 Lupin submits ANDA to FDA
2020-11-24 Astellas files suit against Lupin on related U.S. Patent No. 10,842,780
2022-09-28 Lupin receives final FDA approval for its ANDA products
2023-07-28 Astellas files suit against Lupin on related U.S. Patent No. 11,707,451
2024-04-19 Lupin commercially launches its 25 mg ANDA product
2024-09-04 Lupin commercially launches its 50 mg ANDA product
2024-09-24 U.S. Patent No. 12,097,189 issues
2024-09-24 Complaint Filing Date

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

U.S. Patent No. 12,097,189 - "Pharmaceutical Composition for Modified Release"

  • Patent Identification: U.S. Patent No. 12,097,189, "Pharmaceutical Composition for Modified Release," issued September 24, 2024 (the "’189 Patent").

The Invention Explained

  • Problem Addressed: The patent's background section describes clinical trials of conventional, immediate-release formulations of the active ingredient, mirabegron, which revealed that "pharmacokinetic data unexpectedly varied according to the presence or absence of the intake of food" (’189 Patent, col. 1:50-54). Specifically, taking the drug with food resulted in a significant (67%) decrease in the maximum blood drug concentration (Cmax) compared to taking it in a fasted state, leading to unpredictable therapeutic effects (’189 Patent, col. 1:54-60).
  • The Patented Solution: The invention is a modified-release pharmaceutical composition designed to control the release rate of mirabegron to reduce or eliminate the "food effect" (’189 Patent, col. 2:20-29). By creating a formulation that provides "continuous drug release for 4 hours or more," the invention makes the formulation's release profile, rather than food-related physiological changes in the gut, the rate-limiting step for drug absorption, thereby ensuring more consistent pharmacokinetics (’189 Patent, col. 2:42-53).
  • Technical Importance: Developing formulations that mitigate food effects is significant in pharmacology as it enhances patient safety by avoiding dangerously high Cmax levels in a fasted state and ensures consistent efficacy by preventing sub-therapeutic levels in a fed state, improving patient compliance and overall treatment outcomes.

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the ’189 Patent (Compl. ¶63). Independent claims 1 and 16 are representative method of use claims.
  • Independent Claim 16 includes the following essential elements:
    • A method for treating overactive bladder with a reduced food effect.
    • Administering orally a tablet with 50 mg of mirabegron in a sustained release hydrogel-forming formulation.
    • The formulation comprises a carrier and provides continuous drug release for at least 4 hours.
    • The reduced food effect is defined as a difference in the rate of decrease of Cmax of 10% or more when compared to an immediate-release capsule formulation.
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

  • Lupin’s 25 mg and 50 mg mirabegron extended-release tablets, which are the subject of ANDA No. 209485 ("Lupin's ANDA Products") (Compl. ¶6).

Functionality and Market Context

  • The complaint alleges that Lupin's ANDA Products are generic versions of Astellas's Myrbetriq® tablets and are indicated for the treatment of overactive bladder (Compl. ¶3, ¶59). The complaint provides a chemical structure for the active ingredient mirabegron (Compl. ¶28). The products are described as "sustained release hydrogel-forming formulations" containing either 25 mg or 50 mg of mirabegron (Compl. ¶58).
  • The complaint alleges that because Lupin's products are required by the FDA to be bioequivalent to Myrbetriq®, and because Myrbetriq® itself exhibits the properties of continuous drug release and a reduced food effect, Lupin's products necessarily have these same properties (Compl. ¶56). The prescribing information for Lupin's products is alleged to be a substantive copy of the Myrbetriq® label, instructing oral use for treating overactive bladder (Compl. ¶57, ¶59).

IV. Analysis of Infringement Allegations

  • ’189 Patent Infringement Allegations
Claim Element (from Independent Claim 16) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating overactive bladder... comprising administering orally to a subject in need thereof a tablet... Lupin's product label instructs physicians and patients to administer the tablets orally for the treatment of overactive bladder. ¶59 col. 1:44-49
...comprising 50 mg of...(mirabegron)... Lupin markets and sells a 50 mg strength version of its extended-release mirabegron tablets. ¶6, ¶12 col. 2:40-42
...in a sustained release hydrogel-forming formulation... Lupin's ANDA Products are alleged to be sustained release hydrogel-forming formulations comprising polyethylene oxide and polyethylene glycol. ¶58 col. 9:49-54
...wherein the sustained release hydrogel-forming formulation...provides a continuous drug release for at least 4 hours after oral administration... Based on the bioequivalence requirement with Myrbetriq®, Lupin’s ANDA products are alleged to provide continuous drug release for at least 4 hours. ¶56 col. 2:48-53
...wherein the reduced food effect is compared to that after oral administration of an immediate release formulation...and is a difference in a rate of decrease of Cmax of 10% or more... Based on the properties of Myrbetriq®, which Lupin's product must be bioequivalent to, Lupin’s ANDA products are alleged to reduce the food effect by this claimed amount. ¶56 col. 3:23-28
  • Identified Points of Contention:
    • Scope Questions: A potential question is whether the term "sustained release hydrogel-forming formulation" as used in the patent can be construed in a way that excludes the specific formulation used in Lupin's product. The complaint attempts to preempt this by alleging Lupin's formulation contains specific polymers (polyethylene oxide and polyethylene glycol) that are described as components of such formulations in the patent (Compl. ¶58; ’189 Patent, col. 10:11-14).
    • Technical Questions: The infringement theory relies on an inference: because Lupin's product is bioequivalent to Myrbetriq®, it must share the claimed pharmacokinetic properties of Myrbetriq® (Compl. ¶56). A central technical question will be whether the evidence from Lupin's ANDA submission and other clinical data confirms that its product meets the specific, quantitative limitation of a "difference in a rate of decrease of Cmax of 10% or more" compared to an immediate-release formulation, as required by the claim.

V. Key Claim Terms for Construction

  • The Term: "reduced food effect... is a difference in a rate of decrease of Cmax of 10% or more"

    • Context and Importance: This term is the central feature of the invention and is explicitly defined within the claim itself. The entire infringement and validity analysis may hinge on whether the accused product meets this quantitative pharmacokinetic parameter when compared to the specified immediate-release formulation. Practitioners may focus on this term because it quantifies the invention's core contribution over the prior art.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification discusses the goal of reducing food effects in general terms, stating an object is to provide a composition with "no limitations on food intake" (’189 Patent, col. 2:27-29). A party might argue this context informs the numerical limitation.
      • Evidence for a Narrower Interpretation: The claim language provides its own lexicography by defining the "reduced food effect" with a specific numerical value ("10% or more"). The patent's summary section explicitly recites this limitation, indicating its centrality to the claimed invention (’189 Patent, col. 3:23-28).

  • The Term: "sustained release hydrogel-forming formulation"

    • Context and Importance: This term defines the required physical and functional characteristics of the drug delivery vehicle. The infringement analysis depends on whether Lupin's product falls within the technical scope of this term.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent lists a wide array of formulation types that could achieve modified release, suggesting the term is not limited to a single embodiment (’189 Patent, col. 4:62-65).
      • Evidence for a Narrower Interpretation: The specification provides detailed descriptions and examples of hydrogel-forming formulations, focusing on specific polymers like polyethylene oxide and hypromellose and their properties (’189 Patent, col. 10:1-65). A party could argue the term should be limited to formulations with similar characteristics to these disclosed embodiments.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement, stating that Lupin's product label and instructions encourage and direct healthcare professionals and patients to administer the tablets in a manner that directly infringes the patented method (Compl. ¶65). The complaint also alleges contributory infringement on the basis that Lupin's products are a material part of the invention and are not staple articles of commerce suitable for substantial non-infringing use (Compl. ¶66).
  • Willful Infringement: While the counts do not use the word "willful," the prayer for relief seeks "a trebling of damages for Lupin's willful infringement" (Compl. p. 17, ¶G). The complaint alleges that "At least by the filing date of this Complaint, Lupin will have actual knowledge of the '189 Patent," establishing a basis for potential post-suit willfulness (Compl. ¶68).

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

  • A core issue will be one of evidentiary proof: Does the evidence in Lupin's ANDA, including its bioequivalence studies, demonstrate that its product meets the specific, quantitative pharmacokinetic limitations recited in the claims, particularly the "difference in a rate of decrease of Cmax of 10% or more" compared to an immediate-release formulation? The case may turn on whether the properties of the reference drug can be imputed to the generic product for infringement purposes.
  • A second key question will be one of validity: While not detailed in the complaint, the central dispute in this Hatch-Waxman litigation will likely involve whether the claimed method of treatment was obvious. The court will need to determine if achieving the specific, claimed reduction in the "food effect" for mirabegron using known sustained-release technologies would have been obvious to a person of ordinary skill in the art at the time of the invention.