DCT

1:23-cv-00486

Astellas Pharma Inc v. Ascent Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00486, D. Del., 05/03/2023
  • Venue Allegations: Venue is alleged to be proper as Defendant regularly transacts business in Delaware, derives substantial revenue from sales in the state, and has previously availed itself of the legal protections of Delaware courts.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for a generic version of the overactive bladder drug Myrbetriq® constitutes an act of infringement of a patent covering a specific modified-release formulation.
  • Technical Context: The lawsuit concerns pharmaceutical formulations designed for modified or sustained release of an active drug ingredient, a technology crucial for controlling dosing, improving patient compliance, and managing therapeutic effects over time.
  • Key Procedural History: This action was triggered by Defendant Ascent’s submission of an ANDA with a Paragraph IV certification, a formal assertion to the FDA that its proposed generic product does not infringe Plaintiff Astellas's listed patent or that the patent is invalid. The '780 Patent is listed in the FDA's "Orange Book" as covering Myrbetriq®, and the complaint notes its pediatric exclusivity extends its effective term to March 28, 2030.

Case Timeline

Date Event
2008-09-30 '780 Patent Priority Date
2012-06-28 FDA approves New Drug Application for Myrbetriq®
2013-06-20 FDA issues notice regarding bioequivalence guidance for mirabegron
2020-11-24 U.S. Patent No. 10,842,780 is issued
2023-03-22 Ascent sends Notice Letter to Astellas regarding ANDA filing
2023-05-03 Complaint for Patent Infringement filed

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

U.S. Patent No. 10,842,780 - "Pharmaceutical Composition for Modified Release"

Issued: November 24, 2020

The Invention Explained

  • Problem Addressed: The patent’s background section describes a clinical trial for the active ingredient, mirabegron, which revealed that its pharmacokinetic properties—specifically the maximum concentration (Cmax) and total exposure (AUC)—varied significantly depending on whether the patient had recently eaten. This "food effect" could lead to inconsistent therapeutic outcomes (ʼ780 Patent, col. 1:50-61).
  • The Patented Solution: The invention is a modified-release pharmaceutical composition designed to mitigate this food effect. It combines the active ingredient (mirabegron) with two key excipients: (1) a "hydrogel-forming polymer" that controls the drug's release over time, and (2) a highly water-soluble "additive" that ensures water can penetrate the tablet to activate the hydrogel. By making the formulation's release the rate-limiting step for absorption, the invention seeks to provide a more consistent drug concentration in the blood, regardless of food intake (ʼ780 Patent, col. 2:20-30, 48-59; Abstract).
  • Technical Importance: This formulation technology aimed to provide patients and clinicians with a more predictable and reliable oral dosage form, reducing pharmacokinetic variability and potentially improving the safety and efficacy profile of the drug (ʼ780 Patent, col. 2:26-30).

Key Claims at a Glance

  • The complaint asserts "one or more claims" of the '780 Patent (Compl. ¶35). Independent claim 1 is representative:
    • A pharmaceutical composition comprising 10 mg to 200 mg of mirabegron or its salt.
    • The composition is a sustained release hydrogel-forming formulation.
    • The formulation contains a hydrogel-forming polymer with an average molecular weight of 100,000 to 8,000,000, selected from a specific list (e.g., polyethylene oxide, HPMC).
    • The formulation also contains an additive with a specific water solubility (at least 0.1 g/mL), selected from a specific list (e.g., polyethylene glycol, D-mannitol).
    • The composition exhibits a specific drug dissolution rate when tested under defined conditions (USP paddle method, 200 rpm): 39% or less drug released after 1.5 hours, and at least 75% released after 7 hours.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Ascent’s proposed generic mirabegron extended-release tablets (25 mg and 50 mg strengths), for which it filed Abbreviated New Drug Application (ANDA) No. 218172 with the FDA (Compl. ¶6).

Functionality and Market Context

The complaint alleges that Ascent’s ANDA Product contains the same active ingredient as Myrbetriq® and is intended for the same therapeutic use: treatment of overactive bladder (Compl. ¶17, ¶33). To gain FDA approval, the generic product must be bioequivalent to the branded Myrbetriq® tablets (Compl. ¶33). The complaint alleges that in order to meet the dissolution requirements for bioequivalence, Ascent's product must use a hydrogel formulation equivalent to that covered by the ’780 Patent (Compl. ¶39). The complaint includes a depiction of the chemical structure for mirabegron, the active ingredient in both the branded and accused generic products (Compl. ¶16).

IV. Analysis of Infringement Allegations

'780 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
a pharmaceutical composition, 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 Ascent's ANDA Product contains either 25 mg or 50 mg of the active ingredient mirabegron in extended-release tablets. ¶38 col. 1:33-40; col. 20:20-24
in a sustained release hydrogel-forming formulation comprising a hydrogel-forming polymer having an average molecular weight of 100,000 to 8,000,000...wherein the hydrogel-forming polymer is at least one compound selected from the group consisting of polyethylene oxide, hydroxypropyl methylcellulose... Ascent’s ANDA Product is alleged to contain a "hydrogel-forming polymer" that is covered by the claims of the '780 Patent. ¶40, ¶41 col. 20:26-34
and an additive having a water solubility of at least 0.1 g/mL at 20±5° C., wherein the additive is at least one selected from the group consisting of polyethylene glycol, polyvinylpyrrolidone... Ascent’s ANDA Product is alleged to contain an "additive" that meets the claim limitations. ¶40, ¶41 col. 20:25-26, 35-43
wherein a drug dissolution rate from the pharmaceutical composition is 39% or less after 1.5 hours, and at least 75% after 7 hours, as measured in accordance with United States Pharmacopoeia... at a paddle rotation speed of 200 rpm Ascent's ANDA Product is alleged to have a dissolution profile that meets this limitation, based on the requirement that it be bioequivalent to Myrbetriq® tablets. The complaint references the FDA's "Mirabegron Bioequivalence Guidance" as support for this allegation. The complaint includes a table summarizing the FDA's dissolution testing requirements for mirabegron ANDA filers, which forms part of the basis for the infringement allegation (Compl. ¶30). ¶39, ¶41 col. 20:44-51

Identified Points of Contention

  • Technical Questions: A primary question is whether Ascent’s ANDA product, in fact, meets the specific quantitative limitations of Claim 1. The complaint alleges infringement based on the regulatory requirement of bioequivalence (Compl. ¶39), but the court will require evidence that the accused product's formulation and performance characteristics (e.g., polymer molecular weight, additive solubility, dissolution rate at 200 rpm) actually fall within the claimed ranges. The complaint does not provide specific details on the composition of Ascent's formulation beyond alleging it contains a "hydrogel-forming polymer and an additive" (Compl. ¶40).
  • Scope Questions: The case may turn on whether meeting the FDA’s criteria for bioequivalence necessarily equates to infringing the specific limitations of the patent. The patent claims a specific dissolution profile under a specific test condition (200 rpm paddle speed), and a key question will be whether the FDA's bioequivalence guidance (which, as presented in the complaint, specifies a 100 rpm basket method) mandates a result that also infringes the patent's different testing-condition limitation.

V. Key Claim Terms for Construction

The complaint provides limited detail for claim construction analysis, as it relies on a theory of necessary equivalence rather than mapping specific product features to claim terms.

  • "a drug dissolution rate from the pharmaceutical composition is 39% or less after 1.5 hours, and at least 75% after 7 hours, as measured in accordance with United States Pharmacopoeia in 900 mL of a USP buffer having a pH of 6.8 at a paddle rotation speed of 200 rpm"
    • Context and Importance: This limitation defines the functional performance of the invention. Infringement will hinge on whether Ascent's product exhibits this exact dissolution profile under these exact testing conditions. Practitioners may focus on this term because the complaint's infringement theory links it to FDA bioequivalence standards, which may use different testing parameters (Compl. ¶30).
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A party might argue that the claim should be understood functionally to cover any formulation that solves the "food effect" problem, as this is the stated goal of the invention (ʼ780 Patent, col. 2:26-30).
      • Evidence for a Narrower Interpretation: The claim language is highly specific, reciting a test method (USP paddle), medium (USP buffer pH 6.8), volume (900 mL), and speed (200 rpm). A party would argue these parameters are strict limitations and any deviation, such as the 100 rpm basket method mentioned in the FDA guidance table (Compl. ¶30), falls outside the claim scope. The patent's own examples and stability tests also reference these specific conditions (ʼ780 Patent, col. 14:55-62; col. 15:16-22).

VI. Other Allegations

Indirect Infringement

The complaint alleges both contributory and induced infringement. The claim for induced infringement is based on allegations that Ascent has knowledge of the '780 Patent and intends for its product to be used in an infringing manner upon FDA approval (Compl. ¶54, ¶57). The claim for contributory infringement alleges that Ascent's ANDA product is a material component of the patented invention and has no substantial non-infringing uses (Compl. ¶46).

Willful Infringement

While not pleaded as a separate count, the complaint requests a declaration that the case is "exceptional" under 35 U.S.C. § 285, which is the statutory basis for awarding enhanced damages and attorney fees (Compl. p. 12, ¶F). This request is supported by the allegation that Ascent knew of the '780 Patent at the time it filed its ANDA (Compl. ¶54).

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

  • A central issue will be one of evidentiary proof: Can Astellas demonstrate that Ascent's specific formulation—the details of which are contained within its confidential ANDA filing—actually uses the types of polymers and additives recited in the claims and, critically, exhibits the precise dissolution profile under the exact testing conditions required by Claim 1?
  • The case will also present a key legal and factual question: Does meeting the FDA's regulatory standard for "bioequivalence" to Myrbetriq® necessarily and automatically mean that a generic product infringes the specific, quantitative limitations of the '780 Patent's claims, particularly where the testing parameters cited in the patent and the FDA guidance appear to differ?