DCT

1:24-cv-00940

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-00940, D. Del., 08/13/2024
  • Venue Allegations: Plaintiff alleges venue is proper in Delaware based on Defendants' systematic and continuous business contacts within the state, sales of products including the accused products in Delaware, and a history of not challenging venue in prior Delaware lawsuits.
  • Core Dispute: Plaintiff alleges that Defendant’s generic mirabegron extended-release tablets, the subject of ANDA No. 209488, infringe a newly issued patent covering specific pharmaceutical formulations designed to control drug release.
  • Technical Context: The technology concerns extended-release oral drug formulations for treating overactive bladder, specifically engineered to reduce pharmacokinetic variability ("food effects") that can occur when a drug is taken with or without food.
  • Key Procedural History: The complaint notes prior litigation between the parties involving a related patent, U.S. Patent No. 10,842,780. In that case, Defendant allegedly stipulated that its generic product infringed all asserted claim limitations except for a specific drug dissolution rate profile. The current lawsuit, filed on the day the patent-in-suit issued, asserts that the accused product now meets an identical dissolution rate limitation, and follows Defendant's commercial launch of the generic product.

Case Timeline

Date Event
2008-09-30 '409 Patent - Earliest Priority Date
2016-09-06 Zydus's 2016 Notice Letter to Plaintiffs
2018-07-06 Zydus's 2018 Notice Letter to Plaintiffs
2020-11-24 Astellas files suit against Zydus on related '780 Patent
2021-03-03 Zydus's 2021 Notice Letter to Plaintiffs
2022-09-29 Zydus receives final FDA approval for its ANDA
2024-04-19 Zydus commercially launches its ANDA Products
2024-08-13 U.S. Patent No. 12,059,409 issues
2024-08-13 Complaint filed

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

U.S. Patent No. 12,059,409 - "Pharmaceutical Composition for Modified Release"

  • Issued: August 13, 2024

The Invention Explained

  • Problem Addressed: The patent’s background section states that conventional formulations of the active ingredient, mirabegron, exhibit a significant "food effect," where pharmacokinetic data such as maximum concentration (Cmax) and total exposure (AUC) "unexpectedly varied according to the presence or absence of the intake of food" (ʼ409 Patent, col. 1:55-59). This variability could lead to unpredictable drug performance in patients (ʼ409 Patent, col. 1:65-col. 2:2).
  • The Patented Solution: The invention is a modified-release tablet that controls the drug's release over an extended period. It achieves this by combining the active ingredient with two specific types of excipients: a "hydrogel-forming polymer" (polyethylene oxide) that slows drug release and a highly water-soluble "additive" (polyethylene glycol) that ensures water penetrates the tablet to initiate the hydrogel formation (ʼ409 Patent, col. 2:3-8, col. 6:5-12). This design makes the tablet's dissolution the rate-limiting step of absorption, thereby reducing the impact of food in the gastrointestinal tract (ʼ409 Patent, col. 2:55-63).
  • Technical Importance: Developing formulations that mitigate food effects is critical for ensuring consistent and predictable therapeutic outcomes, which enhances patient safety and drug efficacy (ʼ409 Patent, col. 2:63-col. 3:5).

Key Claims at a Glance

  • The complaint asserts infringement of at least Claim 1 (Compl. ¶46).
  • The essential elements of independent Claim 1 are:
    • A tablet comprising 10 mg to 200 mg of mirabegron or its salt.
    • In a sustained release hydrogel-forming formulation.
    • The formulation comprises a hydrogel-forming polymer which is polyethylene oxide with an average molecular weight of 200,000 to 7,000,000.
    • The formulation also comprises an additive which is polyethylene glycol with a water solubility of at least 0.1 g/mL at 20±5 °C.
    • A drug dissolution rate from the tablet of 39% or less after 1.5 hours, and at least 75% after 7 hours, under specified USP test conditions.
  • The complaint does not explicitly reserve the right to assert other claims, but standard practice allows for amendment.

III. The Accused Instrumentality

Product Identification

  • Zydus's 25 mg and 50 mg mirabegron extended-release oral tablets, which are the subject of Abbreviated New Drug Application (ANDA) No. 209488 (Compl. ¶6).

Functionality and Market Context

  • The accused products are generic versions of Plaintiff's Myrbetriq® tablets and are indicated for the treatment of overactive bladder (Compl. ¶¶6, 26). The complaint identifies the active ingredient as mirabegron and provides its chemical structure (Compl. ¶25). The complaint alleges the products utilize a "sustained release hydrogel-forming formulation" that contains polyethylene oxide as a hydrogel-forming polymer and polyethylene glycol as an additive (Compl. ¶¶51-52).
  • The complaint alleges the products are marketed as "AB rated to 'Brand Equivalent: Myrbetriq®'" and were commercially launched on or about April 19, 2024 (Compl. ¶¶12, 34).

IV. Analysis of Infringement Allegations

'409 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A tablet comprising 10 mg to 200 mg of (R)-2-(2-aminothiazol-4-yl)-4'-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide, or a pharmaceutically acceptable salt thereof Zydus’s ANDA Products are tablets containing either 25 mg or 50 mg of mirabegron. ¶50 col. 22:18-22
in a sustained release hydrogel-forming formulation comprising a hydrogel-forming polymer having an average molecular weight of 200,000 to 7,000,000 Zydus’s ANDA Products are alleged to be sustained-release hydrogel-forming compositions containing polyethylene oxide with average molecular weights of 200,000 and 2,000,000. ¶¶48, 51, 53 col. 8:10-24
wherein the hydrogel-forming polymer is polyethylene oxide Zydus’s ANDA Products contain polyethylene oxide as a hydrogel-forming polymer. ¶¶51, 52 col. 8:1-3
and an additive having a water solubility of at least 0.1 g/mL at 20±5 °C. Zydus’s ANDA Products contain polyethylene glycol (PEG 6000 and PEG 8000), which the complaint alleges have the requisite water solubility, citing stipulations from a prior case. ¶¶49, 54 col. 10:26-35
wherein the additive is polyethylene glycol Zydus’s ANDA Products contain polyethylene glycol 6000 and polyethylene glycol 8000 as additives. ¶54 col. 10:40-43
wherein a drug dissolution rate from the tablet is 39% or less after 1.5 hours, and at least 75% after 7 hours, as measured in accordance with United States Pharmacopoeia... Samples from commercial batches of Zydus’s ANDA Products were allegedly tested and found to meet this specific dissolution limitation. ¶58 col. 6:40-50
  • Identified Points of Contention:
    • Evidentiary Question: The complaint's infringement theory relies heavily on stipulations from prior litigation for most claim elements (Compl. ¶¶48, 49). The central dispute in the prior litigation on the related '780 patent concerned an identical dissolution rate limitation (Compl. ¶32). The key question is whether Plaintiff's testing data, referenced as Exhibit I, will be sufficient to prove that Defendant’s commercially launched product factually meets the specific quantitative dissolution profile required by Claim 1 of the ’409 patent. The case may turn on a battle of experts regarding the methodology and reproducibility of this dissolution testing.
    • Legal Question: A secondary question may concern the legal effect of Defendant's stipulations in the '780 patent case. Practitioners will observe whether arguments of judicial estoppel or issue preclusion will be raised to prevent Defendant from re-litigating whether its product contains the claimed components (e.g., polyethylene oxide, polyethylene glycol) or has the stipulated properties (e.g., molecular weight).

V. Key Claim Terms for Construction

The specificity of the claim limitations and the extensive litigation history between the parties may reduce the number of terms requiring formal construction. However, the following term could be a focus.

  • The Term: "average molecular weight"
  • Context and Importance: Claim 1 requires the polyethylene oxide to have an "average molecular weight of 200,000 to 7,000,000." While the complaint alleges Zydus's product uses polymers squarely within this range (200,000 and 2,000,000), disputes can arise over the specific method used to calculate an "average" for a polymer distribution (e.g., weight-average vs. number-average molecular weight) (Compl. ¶53). Practitioners may focus on this term if Defendant seeks to distinguish its product from the claim scope or challenge the applicability of its prior litigation stipulations, which related to a broader molecular weight range in the '780 patent (Compl. ¶49).
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The term "average molecular weight" is used without a modifier (e.g., "weight-average"), which a party could argue allows for any standard industry method of calculation that results in a value within the claimed range.
    • Evidence for a Narrower Interpretation: The specification lists specific commercial examples of polyethylene oxide, such as "Polyox WSR-N-80 [average molecular weight: 200,000]" and "Polyox WSR-303 [average molecular weight: 7,000,000]," which directly correspond to the boundaries of the claimed range (ʼ409 Patent, col. 8:1-24). A party could argue that the term should be construed consistently with the properties of these specific cited examples.

VI. Other Allegations

  • Indirect Infringement: The complaint's allegations focus on direct infringement under 35 U.S.C. § 271(a) for the commercial sale of the accused product and § 271(e)(2) for the filing of the ANDA (Compl. ¶¶46, 57). The complaint does not contain specific factual allegations supporting indirect infringement.
  • Willful Infringement: Willfulness is alleged based on Defendant's continuation of infringing activities after the filing and service of the complaint (Compl. ¶59). The complaint posits that upon notice, Defendant will have actual knowledge of the '409 patent, and any continued infringement would be willful (Compl. ¶59).

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

  • A core issue will be one of evidentiary proof: Can Astellas present sufficient and credible scientific evidence, likely through expert testing and testimony, to demonstrate that Zydus's commercially available generic tablets meet the precise, quantitative drug dissolution rate limitation defined in Claim 1?
  • A key procedural question will be the preclusive effect of prior admissions: To what extent will Zydus's stipulations from the earlier litigation on the related '780 patent—concerning its product's fundamental composition and characteristics—bar it from contesting those same facts in this new case? The court's handling of this issue will significantly shape the scope of discovery and trial.