DCT

1:23-cv-00022

Astellas Pharma Inc v. Qilu Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00022, D. Del., 01/10/2023
  • Venue Allegations: Venue is alleged based on Defendants’ business transactions and revenue derived from sales within Delaware, as well as purposeful availment of Delaware law. For the foreign defendant, jurisdiction is asserted based on contacts with the United States as a whole.
  • Core Dispute: Plaintiff alleges that Defendants' 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 modified-release pharmaceutical formulation.
  • Technical Context: The technology concerns extended-release pharmaceutical formulations designed to deliver the active ingredient mirabegron in a manner that reduces variations in drug absorption when taken with or without food.
  • Key Procedural History: The lawsuit is a Hatch-Waxman action initiated in response to a Notice Letter dated November 28, 2022. In the letter, Defendants informed Plaintiffs of their ANDA filing and 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, and/or will not be infringed by their proposed generic product.

Case Timeline

Date Event
2008-09-30 '780 Patent Priority Date
2012-06-28 FDA approves NDA for Myrbetriq® extended-release tablets
2013-05-09 FDA updates website with mirabegron bioequivalence guidance
2020-11-24 U.S. Patent No. 10,842,780 Issued
2022-11-28 Defendants send Paragraph IV Notice Letter to Plaintiffs
2023-01-10 Complaint Filed

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

  • Patent Identification: U.S. Patent No. 10,842,780, "Pharmaceutical Composition for Modified Release," issued November 24, 2020. (Compl. ¶23; ’780 Patent, front page).
  • The Invention Explained:
    • Problem Addressed: The patent's background section describes how clinical trials of conventional, rapid-release formulations of the active ingredient (mirabegron) revealed an undesirable "food effect," where pharmacokinetic results, such as the maximum plasma concentration (Cmax) and total drug exposure (AUC), varied significantly depending on whether the drug was taken with food. (’780 Patent, col. 5:50-60).
    • The Patented Solution: The invention claims to solve this problem with a modified-release formulation that controls the drug's release over an extended period, thereby reducing the impact of food on its absorption. (’780 Patent, col. 6:10-14, 6:50-59). The formulation combines the active ingredient with two key excipients: a "hydrogel-forming polymer" that creates a gel matrix to slow drug release, and a highly soluble "additive" that functions as a hydrophilic base to ensure water can penetrate the tablet and activate the gel. (’780 Patent, Abstract; col. 5:61-68).
    • Technical Importance: Formulations that mitigate food effects are valuable in pharmaceutical development because they can lead to more consistent and predictable drug efficacy and safety for patients, regardless of their meal schedules. (’780 Patent, col. 6:20-25).
  • Key Claims at a Glance:
    • The complaint asserts infringement of "one or more claims" of the ’780 Patent. Independent claim 1 is representative. (Compl. ¶36).
    • The essential elements of independent claim 1 include:
      • A pharmaceutical composition in a sustained release hydrogel-forming formulation containing 10-200 mg of mirabegron.
      • A "hydrogel-forming polymer" with an average molecular weight between 100,000 and 8,000,000, selected from a specific list (e.g., polyethylene oxide, HPMC).
      • An "additive" with a water solubility of at least 0.1 g/mL, selected from a specific list (e.g., polyethylene glycol, D-mannitol).
      • A specific in vitro drug dissolution profile: 39% or less of the drug is released after 1.5 hours, and at least 75% is released after 7 hours, under specified USP test conditions.
    • The complaint's general allegation of infringing "one or more claims" implicitly reserves the right to assert other independent or dependent claims. (Compl. ¶¶39-40).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is "Qilu's ANDA Product," identified as mirabegron extended-release tablets, 25 mg and 50 mg, for which Defendants filed ANDA No. 217989. (Compl. ¶7).
  • Functionality and Market Context: The complaint alleges that Qilu's ANDA Product is a generic version of Myrbetriq® that will have the same active ingredient, dosage form, and dosage amounts. (Compl. ¶34). It is alleged that to gain FDA approval, the product must be "bioequivalent" to Myrbetriq® tablets. (Compl. ¶34). The complaint further alleges that to meet the FDA's bioequivalence guidance, which includes specific dissolution requirements, Qilu's product must have "equivalent dissolution properties" to Myrbetriq®. (Compl. ¶39). The complaint provides a table summarizing the FDA's dissolution testing guidance for mirabegron ANDAs. (Compl. p. 7). Based on this regulatory requirement and the assertion that Myrbetriq® is covered by the ’780 Patent, the complaint alleges that Qilu's ANDA Product "uses a hydrogel formulation, the same as or equivalent to the Myrbetriq® Tablets formulation." (Compl. ¶¶30, 39).

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...in a sustained release hydrogel-forming formulation comprising a hydrogel-forming polymer...and an additive... Qilu's ANDA Product is an extended-release tablet that, on information and belief, "uses a hydrogel formulation, the same as or equivalent to the Myrbetriq® Tablets formulation" in order to achieve the required bioequivalence. ¶¶38, 39 col. 20:19-31
wherein the hydrogel-forming polymer is at least one compound selected from the group consisting of polyethylene oxide, hydroxypropyl methylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose sodium, hydroxyethyl cellulose, and a carboxyvinyl polymer... The complaint does not identify the specific polymer in the accused product but alleges the formulation is "the same as or equivalent to" the patented formulation. ¶39 col. 20:32-38
wherein the additive is at least one selected from the group consisting of polyethylene glycol, polyvinylpyrrolidone, D-mannitol... The complaint does not identify the specific additive in the accused product but makes its allegation based on the requirement of bioequivalence. ¶39 col. 20:39-44
and 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 in 900 mL of a USP buffer having a pH of 6.8 at a paddle rotation speed of 200 rpm. The complaint alleges that Qilu's product will have "equivalent dissolution properties" to Myrbetriq® Tablets, which are alleged to meet a dissolution profile of "39% or less...after 1.5 hours, and at least 75%...after 7 hours," mirroring the claim language. A table of FDA dissolution requirements is cited as support. ¶¶21, 32, 39, p. 7 col. 20:46-52
  • Identified Points of Contention:
    • Evidentiary Questions: The complaint's infringement theory appears to be largely inferential. It does not provide direct evidence of the accused product's composition but alleges that the product must infringe to meet the FDA's regulatory requirement for bioequivalence with Myrbetriq®. A central question will be what discovery reveals about the actual composition of Qilu's formulation. Does it contain a "hydrogel-forming polymer" and an "additive" that literally meet the claim limitations regarding molecular weight, solubility, and selection from the claimed lists?
    • Technical Questions: A key technical question is whether achieving bioequivalence necessitates using the specific formulation claimed in the patent. The dispute may center on whether an alternative, non-infringing formulation could produce a dissolution profile that is "equivalent" for regulatory purposes but not literally infringing. This raises the question of how the dissolution data from the accused product will compare to the precise numerical limits recited in the claim.

V. Key Claim Terms for Construction

  • The Term: "hydrogel-forming polymer"

  • Context and Importance: This term defines the primary release-controlling agent in the claimed formulation. Its construction is critical because it determines the scope of polymer technologies covered by the patent. Practitioners may focus on this term to dispute whether the excipient used in the accused product, even if it provides sustained release, functions by forming a "hydrogel" as contemplated by the patent.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification lists several distinct classes of polymers as examples, including polyethylene oxides and various celluloses, suggesting the term is not limited to a single chemical type. (’780 Patent, col. 9:43-49).
    • Evidence for a Narrower Interpretation: The patent repeatedly links the polymer to the function of forming a hydrogel to control drug release, and provides specific, exemplary viscosity and molecular weight ranges that give context to the term. (’780 Patent, col. 5:61-68, col. 9:20-33). A party could argue the term is limited to polymers that exhibit these specific physical properties and gel-forming mechanism, rather than any polymer that happens to sustain release.

  • The Term: "additive having a water solubility of at least 0.1 g/mL"

  • Context and Importance: This limitation defines the second key component, which facilitates water penetration. The dispute will turn on whether an excipient in the accused product meets both the structural requirement (being on the list) and the functional/physical requirement (solubility).

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: Claim 1 itself defines the additive by a clear, quantitative solubility threshold (≥0.1 g/mL), suggesting any listed compound meeting this objective measure falls within the scope. (’780 Patent, col. 20:25-26).
    • Evidence for a Narrower Interpretation: The specification describes this component functionally as an "additive which ensures penetration of water." (’780 Patent, Abstract). A party could argue that this requires not only meeting the solubility threshold but also demonstrating that this function is achieved in the formulation, potentially limiting the claim to compositions where this effect is integral to the hydrogel's proper function.

VI. Other Allegations

  • Indirect Infringement: The complaint pleads both contributory and induced infringement in the alternative.
    • Contributory (Count II): It is alleged that Qilu's ANDA Product is a material part of the patented invention, has no substantial non-infringing uses, and that Defendants have knowledge thereof. (Compl. ¶¶44-45).
    • Induced (Count III): The complaint alleges that upon approval, Defendants will instruct and encourage others (e.g., doctors, patients) to use the product in an infringing manner. (Compl. ¶¶50-51). Knowledge of the patent and intent to cause infringement are alleged based on Defendants' filing of an ANDA for a product whose intended use is allegedly covered by the patent's claims. (Compl. ¶¶52-55).
  • Willful Infringement: The complaint does not use the term "willful," but it requests a finding that the case is "exceptional" and an award of attorney fees under 35 U.S.C. § 285. (Compl., Prayer for Relief ¶F). The factual basis for this appears to be pre-suit knowledge of the patent, evidenced by the November 28, 2022 Notice Letter sent by Defendants in connection with their Paragraph IV certification. (Compl. ¶7).

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

  • A central issue will be one of evidentiary proof versus regulatory inference: Can Astellas prove through direct evidence that Qilu's formulation literally contains the specific components recited in the claims, or will it have to rely on the argument that achieving regulatory bioequivalence with Myrbetriq® necessarily requires infringing the patent? The case as pleaded leans heavily on the latter, making discovery into the accused product's exact composition critical.
  • The case will likely involve a key question of functional equivalence versus literal composition: Does Qilu's product achieve its FDA-required dissolution profile using the specific "hydrogel-forming polymer" and high-solubility "additive" combination claimed by the ’780 Patent, or does it employ an alternative, compositionally distinct formulation that is merely functionally equivalent for regulatory purposes?
  • A third core question will concern claim construction and infringement boundaries: How will the court construe the term "hydrogel-forming formulation"? The infringement analysis will depend on whether this term is defined broadly by its chemical class and sustained-release function, or more narrowly by the specific gel-forming mechanisms and physical properties described in the patent's specification.