DCT

2:23-cv-00125

Astellas Pharma Inc v. Qilu Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:23-cv-00125, E.D. Pa., 01/11/2023
  • Venue Allegations: Venue is alleged to be proper based on Defendant Qilu Pharma, Inc.’s incorporation in Pennsylvania and both defendants’ alleged continuous business transactions and revenue derived from sales within the district.
  • Core Dispute: Plaintiff alleges that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to market a generic version of Myrbetriq® infringes a patent related to a modified-release pharmaceutical composition.
  • Technical Context: The technology concerns oral drug delivery formulations for the active ingredient mirabegron, designed to provide a consistent, modified release profile that reduces pharmacokinetic variability caused by food intake.
  • Key Procedural History: This action was filed under the Hatch-Waxman Act following Plaintiffs’ receipt of a November 28, 2022 notice letter from Defendants regarding their filing of ANDA No. 217989. The notice included a Paragraph IV certification asserting that U.S. Patent No. 10,842,780, which is listed in the FDA's Orange Book for Myrbetriq®, is invalid, unenforceable, or will not be infringed by the proposed generic product.

Case Timeline

Date Event
2008-09-30 '780 Patent Priority Date
2012-06-28 FDA approval of Myrbetriq® NDA No. 202611
2020-11-24 U.S. Patent No. 10,842,780 Issues
2022-11-28 Defendants send Qilu's Notice Letter
2023-01-11 Complaint 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 clinical trial results for conventional, immediate-release formulations of the active ingredient, mirabegron. These trials revealed that key pharmacokinetic parameters, such as the maximum plasma concentration (Cmax) and total drug exposure (AUC), "unexpectedly varied according to the presence or absence of the intake of food," with significant decreases observed when the drug was taken with a meal (’780 Patent, col. 6:49-59).
  • The Patented Solution: To solve this "food effect" problem, the invention discloses a modified-release tablet that controls the drug's release rate. The formulation combines the active drug with a "hydrogel-forming polymer" and a highly water-soluble "additive which ensures penetration of water into the pharmaceutical composition" (’780 Patent, Abstract; col. 6:18-29). This combination is designed to make the drug's slow release from the tablet, rather than its absorption in the gastrointestinal tract, the rate-limiting step, thereby reducing pharmacokinetic variability regardless of food intake (’780 Patent, col. 6:50-54).
  • Technical Importance: Achieving a consistent drug-release profile independent of food intake is significant for drugs requiring chronic administration, as it promotes predictable therapeutic effects and enhances patient safety and compliance.

Key Claims at a Glance

  • The complaint asserts "one or more claims" of the ’780 Patent; independent claim 1 is representative of the core technology (Compl. ¶ 37).
  • The essential elements of independent claim 1 include:
    • A pharmaceutical composition comprising 10 mg to 200 mg of mirabegron or a salt thereof.
    • The composition is a "sustained release hydrogel-forming formulation" containing a "hydrogel-forming polymer" with a specific molecular weight range (100,000 to 8,000,000).
    • The formulation also contains an "additive" with a specified high water solubility (at least 0.1 g/mL).
    • The claim recites specific Markush groups for the polymer (e.g., polyethylene oxide) and the additive (e.g., polyethylene glycol).
    • The formulation must exhibit a specific dissolution profile: releasing "39% or less after 1.5 hours, and at least 75% after 7 hours" when measured under specific USP test conditions (paddle method, 200 rpm, pH 6.8 buffer).
  • The complaint does not explicitly reserve the right to assert dependent claims but does so implicitly through its general allegations.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendants' proposed generic mirabegron extended-release tablets (25 mg and 50 mg), for which they seek FDA approval via ANDA No. 217989 ("Qilu ANDA Product") (Compl. ¶¶ 7, 39).

Functionality and Market Context

  • The Qilu ANDA Product is intended as a generic equivalent to Plaintiffs' Myrbetriq® tablets for treating overactive bladder (Compl. ¶¶ 7, 19).
  • The complaint alleges that to gain FDA approval, the Qilu ANDA Product must be bioequivalent to Myrbetriq® (Compl. ¶ 35). This requirement, according to the complaint, means the Qilu ANDA Product must have "equivalent dissolution properties" to Myrbetriq® (Compl. ¶ 40).
  • Based on this regulatory requirement, the complaint alleges on "information and belief" that because Myrbetriq® utilizes a hydrogel formulation, the Qilu ANDA Product must also use a "hydrogel formulation, the same as or equivalent to the Myrbetriq® Tablets formulation," which is allegedly covered by the ’780 Patent (Compl. ¶ 40).
  • The complaint provides the chemical structure of mirabegron, the active ingredient in both the patented and accused products (Compl. ¶ 18).
  • A table from the FDA's "Mirabegron Bioequivalence Guidance" is included, outlining dissolution testing requirements for ANDA filers (Compl. ¶ 32).

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart. The infringement theory is based on the allegation that the accused generic product, in order to be bioequivalent to the reference Myrbetriq® product, must necessarily adopt the formulation and performance characteristics claimed in the ’780 Patent.

'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...mirabegron... The Qilu ANDA Product is alleged to contain 25 mg or 50 mg of mirabegron. ¶39 col. 19:20-23
in a sustained release hydrogel-forming formulation... The complaint alleges on information and belief that the Qilu ANDA Product uses a hydrogel formulation equivalent to that of Myrbetriq® tablets to meet bioequivalence requirements. ¶40 col. 19:23-26
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. The complaint alleges Myrbetriq® meets this dissolution profile and that the Qilu ANDA Product will have equivalent properties. ¶¶22, 40 col. 20:39-49
  • Identified Points of Contention:
    • Technical Question: What evidence supports the allegation that the Qilu ANDA Product meets the specific dissolution rate limitations of claim 1? The complaint’s theory is inferential, based on the premise that FDA bioequivalence requirements necessitate that the accused product mimics the dissolution profile of Myrbetriq®, which is alleged to meet the claim limitations (Compl. ¶¶ 22, 40).
    • Scope Questions: A central dispute may be whether achieving "bioequivalence" to Myrbetriq® requires infringement. It raises the question of whether a different, non-infringing formulation could produce a sufficiently similar pharmacokinetic profile to satisfy FDA standards.
    • Scope Questions: The complaint includes an FDA guidance document specifying a dissolution test using USP Apparatus I (Basket) (Compl. ¶ 32), whereas claim 1 of the ’780 Patent requires a test using USP Apparatus II (paddle) at a different rotation speed (’780 Patent, col. 20:42-49). This discrepancy raises the question of whether adherence to the FDA guidance for bioequivalence necessarily establishes that the accused product infringes a claim reciting a different test methodology.

V. Key Claim Terms for Construction

  • The Term: "hydrogel-forming formulation"

    • Context and Importance: This term is foundational to the claimed invention, defining the drug delivery matrix. The infringement case hinges on whether the Qilu ANDA Product, whose specific composition is not detailed in the complaint, is determined to be a "hydrogel-forming formulation" as claimed. Practitioners may focus on this term because the allegation of its presence in the accused product is based on inference rather than direct evidence (Compl. ¶ 40).
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent specification describes the invention functionally as a combination of an active ingredient, a "hydrogel-forming polymer," and an "additive which ensures penetration of water" (’780 Patent, col. 6:23-29). This could support a construction covering any formulation that achieves this structure and function.
      • Evidence for a Narrower Interpretation: The patent provides specific examples of suitable polymers (e.g., polyethylene oxide, HPMC) and additives (e.g., polyethylene glycol) (’780 Patent, col. 8:49-53; col. 10:17-43). A party could argue the term should be construed as limited to formulations comprising excipients from these disclosed classes.

  • The Term: "additive having a water solubility of at least 0.1 g/mL at 20±5° C."

    • Context and Importance: This limitation recites a specific, quantitative physical property of a key excipient. Proving infringement will require evidence that an additive in the Qilu ANDA Product meets this precise solubility threshold. The complaint does not provide such evidence.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent discloses a lengthy Markush group of potential additives that could meet this requirement, suggesting a wide range of possible substances (’780 Patent, col. 10:17-43).
      • Evidence for a Narrower Interpretation: The claim presents a clear, numerical boundary ("at least 0.1 g/mL"). The specification reinforces this, stating that the volume of water needed to dissolve 1 g of the additive is "10 mL or less," which directly corresponds to the claimed solubility (’780 Patent, col. 10:8-11). This suggests the term should be applied as a strict, measurable limitation.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both contributory and induced infringement. The contributory infringement claim is based on the allegation that the Qilu ANDA Product is a material part of the patented invention with no substantial non-infringing use (Compl. ¶¶ 45-46). The induced infringement claim alleges that upon approval, Defendants will market the product for its intended, infringing use, with knowledge of the patent and with the specific intent to cause infringement (Compl. ¶¶ 51-56).
  • Willful Infringement: While the complaint does not use the term "willful," it requests a finding that the case is "exceptional" under 35 U.S.C. § 285 (Compl., Prayer for Relief F). This allegation appears to be based on Defendants’ alleged knowledge of the ’780 Patent, via its Orange Book listing and the notice letter procedure, at the time of committing the alleged act of infringement (filing the ANDA) (Compl. ¶¶ 7-8, 23).

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

  • A core issue will be one of evidentiary proof: can Astellas establish that Qilu’s proposed generic product—whose exact formulation is not yet known—infringes the specific compositional and dissolution-rate limitations of the ’780 patent claims? The case may depend on whether conformity with FDA bioequivalence guidance for Myrbetriq® is legally and factually sufficient to prove infringement.
  • A key technical question will be one of methodological relevance: does the difference between the USP Apparatus I test in the FDA's guidance and the USP Apparatus II test recited in claim 1 provide Qilu with a viable non-infringement argument?
  • The litigation will also likely turn on a question of definitional scope: will the term "hydrogel-forming formulation" be construed broadly based on its described function, or will it be limited more narrowly to the specific classes of excipients detailed in the patent's embodiments?