DCT

2:23-cv-03372

Astellas Pharma Inc v. Ascent Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:23-cv-03372, E.D.N.Y., 05/04/2023
  • Venue Allegations: Venue is alleged to be proper as the Defendant is a New York corporation with its principal place of business in Central Islip, New York, which is within the Eastern District of New York.
  • Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (ANDA) to market a generic version of the overactive bladder drug Myrbetriq® constitutes an act of infringement of a patent covering a modified-release pharmaceutical formulation.
  • Technical Context: The technology relates to pharmaceutical compositions designed to provide modified (extended) release of a drug, specifically to mitigate the "food effect," where the drug's absorption and efficacy vary depending on whether it is taken with food.
  • Key Procedural History: This is a Hatch-Waxman action initiated in response to Defendant’s ANDA filing (No. 218172) and its associated Paragraph IV certification. The certification asserts that Plaintiff's patent is invalid, unenforceable, or will not be infringed by the proposed generic product. Plaintiff was notified of the ANDA filing via a letter from Defendant dated March 22, 2023.

Case Timeline

Date Event
2008-09-30 '780 Patent Priority Date
2012-06-28 FDA approves NDA for Myrbetriq® tablets
2013-05-09 FDA updates Bioequivalence Guidance for mirabegron
2020-11-24 '780 Patent Issue Date
2023-03-22 Defendant sends notice letter regarding ANDA filing
2023-05-04 Complaint Filing Date

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

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

  • Patent Identification: 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 problem observed in clinical trials of conventional formulations of the active ingredient, mirabegron. Specifically, it notes that "pharmacokinetic data unexpectedly varied according to the presence or absence of the intake of food," a phenomenon known as the "food effect" ('780 Patent, col. 2:50-54). This variability can lead to inconsistent drug levels in a patient's body, potentially affecting both safety and efficacy.
  • The Patented Solution: The invention claims to solve this problem with a modified-release pharmaceutical composition that reduces the food effect ('780 Patent, col. 2:59-62). The composition combines mirabegron with two other key components: (1) a "hydrogel-forming polymer" that controls the rate of drug release over time, and (2) a highly water-soluble "additive which ensures penetration of water into the" tablet, facilitating the hydrogel's formation and the subsequent drug release ('780 Patent, Abstract; col. 2:60-65). By controlling the release mechanism, the formulation aims to make drug absorption the rate-limiting step, thereby minimizing the impact of food in the gastrointestinal tract.
  • Technical Importance: Developing a formulation that mitigates the food effect is significant because it can provide more predictable therapeutic outcomes and simplify dosing regimens for patients, who would not need to coordinate taking the medication with their meals ('780 Patent, col. 2:28-29).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the '780 Patent without specifying them (Compl. ¶35). Independent claims 1 and 22 are the primary composition claims.
  • Essential elements of independent claim 1 include:
    • A pharmaceutical composition comprising 10 mg to 200 mg of mirabegron in a sustained release hydrogel-forming formulation.
    • The formulation includes a "hydrogel-forming polymer" selected from a specific list (polyethylene oxide, hydroxypropyl methylcellulose, etc.).
    • The formulation also includes an "additive" with a specified water solubility (at least 0.1 g/mL) selected from a specific list (polyethylene glycol, D-mannitol, etc.).
    • The composition exhibits a specific drug dissolution profile: "39% or less after 1.5 hours, and at least 75% after 7 hours," when measured under specific test conditions (USP paddle method, 900 mL of pH 6.8 buffer, 200 rpm).
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendant Ascent’s proposed generic mirabegron extended-release tablets (25 mg and 50 mg), as described in its ANDA No. 218172 (Compl. ¶6).

Functionality and Market Context

  • The complaint alleges that Ascent’s ANDA Product contains mirabegron as its active ingredient and is intended for the treatment of overactive bladder (Compl. ¶17, 33). To gain FDA approval, the product must be bioequivalent to the branded Myrbetriq® tablets (Compl. ¶33). The complaint alleges that achieving this bioequivalence requires Ascent's product to have "equivalent dissolution properties" to Myrbetriq®, which in turn allegedly uses a "hydrogel formulation" covered by the '780 Patent (Compl. ¶39). The complaint includes a table from the FDA's "Mirabegron Bioequivalence Guidance" outlining the dissolution testing method required for ANDA filers, which forms a basis for Plaintiff's infringement theory (Compl. ¶30). The complaint also provides a diagram 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, in a sustained release hydrogel-forming formulation Ascent's ANDA Product contains either 25 mg or 50 mg of mirabegron in extended-release tablets and is alleged on information and belief to be a hydrogel forming formulation. ¶38, 41 col. 19:20-24
comprising a hydrogel-forming polymer... On information and belief, Ascent's ANDA Product is alleged to contain a hydrogel-forming polymer that meets the claim limitations. ¶40 col. 19:26-32
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 [a specified list] On information and belief, Ascent's ANDA Product is alleged to contain an additive that meets the claim limitations. ¶40 col. 19:25; 19:33-42
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... The complaint alleges that in order to be bioequivalent to Myrbetriq®, Ascent’s ANDA product will have equivalent dissolution properties to Myrbetriq®, which itself allegedly meets this dissolution profile. ¶20, 39 col. 19:42-49
  • Identified Points of Contention:
    • Scope Questions: The complaint's allegations regarding the specific composition of Ascent's product (i.e., the identity of the hydrogel-forming polymer and the additive) are made "on information and belief" (Compl. ¶40). A central question will be whether the excipients used in Ascent's confidential ANDA formulation fall within the scope of the Markush groups recited in the asserted claims.
    • Technical Questions: The infringement allegation for the dissolution rate limitation is inferential. It assumes that achieving bioequivalence with the branded Myrbetriq® product requires the generic product to meet the patent's claimed dissolution profile (Compl. ¶39). This raises the question of whether Ascent's product literally meets the claimed dissolution profile, or if it achieves bioequivalence through a technically distinct formulation that may not infringe.

V. Key Claim Terms for Construction

  • The Term: "additive which ensures penetration of water into the pharmaceutical composition" (from the patent abstract, referenced in the detailed description and embodied in claim 1's requirements).
  • Context and Importance: This term defines one of the two key excipients responsible for the modified-release properties. Its construction is critical because it will determine what types of substances can meet this limitation. Practitioners may focus on whether this is a purely structural requirement (i.e., being on the list in claim 1) or if it also imposes a functional requirement that a substance must be proven to "ensure penetration of water."
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification provides a long and varied list of substances that can serve as the additive, including polymers, sugar alcohols, saccharides, surfactants, salts, and amino acids. This could support an argument that any substance from that class with the requisite solubility is sufficient ('780 Patent, col. 10:17-43).
    • Evidence for a Narrower Interpretation: A party could argue that the phrase "ensures penetration of water" is a functional requirement that goes beyond merely being soluble. This might require evidence that the chosen additive performs a specific function in the formulation beyond what would be expected of any soluble filler, potentially narrowing the claim scope to exclude some excipients used by the defendant. The patent links the additive to the goal of alleviating the "food effect," which could be argued to tie the term to a specific functional outcome ('780 Patent, col. 2:59-65).

VI. Other Allegations

  • Indirect Infringement: The complaint pleads both induced and contributory infringement. The inducement claim (Count III) is based on the allegation that Ascent intends for its product to be used in an infringing manner and has knowledge of the '780 patent (Compl. ¶54, 57). The contributory infringement claim (Count II) alleges that Ascent's ANDA product is a material part of the invention and has no substantial non-infringing uses (Compl. ¶46-47).
  • Willful Infringement: The complaint does not contain a separate count for willful infringement. However, it alleges that Ascent has had knowledge of the '780 patent since at least the time it sent its notice letter (Compl. ¶54-55) and requests in its prayer for relief a declaration that the case is "exceptional" under 35 U.S.C. § 285, which can be a predicate for awarding enhanced damages or attorney fees (Compl., p. 12, ¶F).

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

  • A core issue will be one of compositional fact: does the confidential formulation in Ascent's ANDA contain a "hydrogel-forming polymer" and an "additive" that fall within the literal scope of the Markush groups defined in the '780 Patent's claims? The case's trajectory will depend heavily on the facts revealed from the ANDA during discovery.
  • A key evidentiary question will be one of inferential proof: can Astellas demonstrate that for Ascent's product to be "bioequivalent" to Myrbetriq®, it must necessarily exhibit the specific dissolution rate profile claimed in the patent? The dispute may center on whether the FDA's regulatory standard of bioequivalence translates directly to a finding of literal patent infringement.