DCT

1:24-cv-01069

Astellas Pharma Inc v. Zydus Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-01069, D. Del., 09/24/2024
  • Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware because Defendants transact business in the state, derive substantial revenue from product sales in Delaware, and have not challenged venue in prior related litigations in the same district.
  • Core Dispute: Plaintiff alleges that Defendant’s generic mirabegron extended-release tablets, marketed for overactive bladder, infringe a patent related to a pharmaceutical formulation designed to reduce the "food effect"—the variation in drug absorption when taken with or without food.
  • Technical Context: The technology concerns modified-release oral drug formulations that provide a consistent pharmacokinetic profile, a key feature for improving therapeutic efficacy and patient compliance for chronic conditions like overactive bladder.
  • Key Procedural History: The parties are engaged in other ongoing patent litigations in the same court concerning different patents covering the same brand-name drug (Myrbetriq®). The current lawsuit involves a patent that issued on the same day the complaint was filed and was therefore not included in the prior suits.

Case Timeline

Date Event
2010-03-29 U.S. Patent No. 12,097,189 Priority Date
2012-06-28 FDA approves Astellas's New Drug Application for Myrbetriq®
2016-09-06 Zydus sends first Notice Letter regarding its ANDA filing
2020-11-24 Astellas files suit against Zydus asserting the ’780 Patent
2022-09-29 Zydus receives final FDA approval for its generic mirabegron ANDA
2023-07-28 Astellas files suit against Zydus asserting the ’451 Patent
2024-04-19 Zydus commercially launches its generic mirabegron products
2024-09-24 U.S. Patent No. 12097189 issues
2024-09-24 Complaint filed

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 how conventional, immediate-release formulations of the active ingredient mirabegron exhibit a significant "food effect." Specifically, when the drug is taken with food, its maximum concentration (Cmax) and total absorption (AUC) in the bloodstream are substantially lower than when taken in a fasted state, which can lead to unpredictable therapeutic outcomes ( Compl. ¶49; ’189 Patent, col. 1:49-59).
  • The Patented Solution: The invention is a modified-release formulation that provides a continuous, sustained release of the drug for at least four hours after oral administration. By controlling the rate of drug release from the tablet, the formulation itself, rather than the presence of food in the gastrointestinal tract, becomes the rate-limiting step for absorption. This approach is designed to reduce the pharmacokinetic variability between fed and fasted states, ensuring more consistent drug delivery ( Compl. ¶37; ’189 Patent, col. 2:47-59).
  • Technical Importance: This technology allows for more consistent dosing and predictable therapeutic effects for a drug used to treat a chronic condition, which may improve patient outcomes and simplify dosing instructions (Compl. ¶37).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the ’189 Patent (Compl. ¶65). The lead independent claims appear to be Claims 1 and 16, which are directed to methods of treatment.
  • Independent Claim 1:
    • A method for treating overactive bladder with a reduced food effect.
    • The method comprises orally administering a tablet with 25 mg of mirabegron.
    • The mirabegron is in a "sustained release hydrogel-forming formulation."
    • The formulation comprises a carrier and provides "a continuous drug release for at least 4 hours after oral administration."
    • The "reduced food effect" is defined as a difference in the rate of Cmax decrease of 10% or more when compared to an immediate-release capsule formulation.
  • Independent Claim 16 is substantively identical to Claim 1 but recites a 50 mg tablet.

III. The Accused Instrumentality

Product Identification

  • The accused products are Zydus’s generic mirabegron extended-release oral tablets in 25 mg and 50 mg strengths, approved under Abbreviated New Drug Application (ANDA) No. 209488 (Compl. ¶8).

Functionality and Market Context

  • The accused products are generic versions of Astellas’s Myrbetriq® tablets and are indicated for the treatment of overactive bladder (Compl. ¶¶8, 32). The complaint provides the chemical structure of the active ingredient, mirabegron (Compl. p. 8). The complaint alleges, on information and belief, that the tablets are "sustained release hydrogel-forming formulations" containing polyethylene oxide and polyethylene glycol (Compl. ¶60). The central technical allegation is that, to gain FDA approval, Zydus had to demonstrate that its products are bioequivalent to Myrbetriq® tablets. The complaint alleges that this bioequivalence requirement means Zydus's products must necessarily share the patented functional properties, including providing continuous drug release for at least four hours and reducing the food effect as claimed (Compl. ¶¶58-59).
  • The products were commercially launched in the U.S. on or about April 19, 2024, as a lower-cost generic alternative to the brand-name Myrbetriq® product (Compl. ¶14).

IV. Analysis of Infringement Allegations

’189 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating overactive bladder... with a reduced food effect... Defendant’s product label instructs oral administration of the tablets for treating overactive bladder; the product allegedly provides a reduced food effect by virtue of its required bioequivalence to the Myrbetriq® reference drug. ¶58, ¶61 col. 2:23-28
...comprising administering orally... a tablet comprising 25 mg of... anilide... Defendant manufactures, markets, and sells 25 mg and 50 mg oral tablets containing mirabegron. ¶8, ¶62 col. 1:33-44
...in a sustained release hydrogel-forming formulation... The complaint alleges on information and belief that the accused products are sustained release hydrogel-forming formulations containing polyethylene oxide and polyethylene glycol. ¶60 col. 9:22-24
...which... provides a continuous drug release for at least 4 hours after oral administration... The complaint alleges that because the accused product is bioequivalent to Myrbetriq®, it likewise provides a continuous drug release for at least 4 hours. ¶58 col. 2:47-52
...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... The complaint alleges that because the accused product is bioequivalent to Myrbetriq®, which exhibits this property, the accused product must also meet this limitation. ¶50, ¶58 col. 3:24-28
  • Identified Points of Contention:
    • Scope Questions: The complaint’s infringement theory rests heavily on regulatory requirements, alleging that because Zydus’s products must be bioequivalent to Myrbetriq®, they must necessarily practice the claimed method. A central question for the court will be whether this inference is a sufficient factual basis for infringement, or if direct evidence of the accused product's specific formulation and in vivo performance is required to prove each claim limitation is met.
    • Technical Questions: A key factual dispute may arise over whether the accused product is, in fact, a "sustained release hydrogel-forming formulation" as claimed. The complaint makes this allegation "on information and belief" based on the product's inactive ingredients list (Compl. ¶60). The defendant may argue its formulation technology is different and falls outside the scope of this claim term.

V. Key Claim Terms for Construction

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

    • Context and Importance: This term defines the core technology of the claimed invention. The infringement analysis depends on whether Defendant's extended-release mechanism falls within the scope of this term.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent specification lists a wide variety of polymers that could be used in such a formulation, including polyethylene oxide, hypromellose, hydroxypropyl cellulose, and carboxyvinyl polymers, suggesting the term is not limited to a single chemical composition ( ’189 Patent, col. 10:14-22).
      • Evidence for a Narrower Interpretation: The detailed examples in the patent focus on formulations comprising specific combinations of polyethylene oxide (PEO) and polyethylene glycol (PEG) ( ’189 Patent, col. 33:40-50 (Example 1A)). A defendant could argue these examples limit the scope of the term to similar PEO/PEG-based systems.

  • The Term: "reduced food effect"

    • Context and Importance: This term describes the functional result of practicing the claimed method. The claim provides its own lexicography, defining the term as "a difference in a rate of decrease of Cmax of 10% or more" compared to an immediate-release capsule.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claim language itself provides a clear, quantitative definition, which may suggest that any formulation meeting this performance metric satisfies the limitation, regardless of the precise mechanism.
      • Evidence for a Narrower Interpretation: Parties may dispute the proper methodology for the comparison, such as the specific composition of the "immediate release formulation" used as the baseline, as described in the patent’s clinical test examples ( ’189 Patent, col. 43:10-44:46). The definition could be construed as being tied to the specific testing parameters disclosed in the patent.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement of infringement, stating that Defendant’s product label and instructions encourage and direct healthcare professionals and patients to orally administer the tablets for the treatment of overactive bladder, thereby practicing the patented method (Compl. ¶67). It also alleges contributory infringement on the basis that the accused tablets are a material part of the invention and are not a staple article suitable for substantial non-infringing use (Compl. ¶68).
  • Willful Infringement: The complaint alleges that Defendant will have actual knowledge of the ’189 Patent at least as of the filing date of the complaint, forming a basis for post-suit willful infringement (Compl. ¶70). The prayer for relief requests treble damages (Compl. p. 17, ¶G).

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

  • A core issue will be one of evidentiary sufficiency: can infringement of a method claim be established primarily through inference based on the accused product's regulatory status as a bioequivalent generic? The case may depend on whether Plaintiff can produce direct evidence confirming the accused product’s formulation and pharmacokinetic performance align with the specific limitations of the claims.
  • A key question will be one of technical and definitional scope: does the term "sustained release hydrogel-forming formulation" encompass the specific technology used in the accused generic product, or is the term limited by the patent's examples to a narrower class of PEO/PEG-based systems? The construction of this term will likely be a central point of contention.