DCT

1:23-cv-00689

Astellas Pharma Inc v. MSN Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00689, D. Del., 06/23/2023
  • Venue Allegations: Venue is alleged to be proper based on Defendant MSN Pharmaceuticals Inc.'s incorporation in Delaware and both defendants' alleged business activities and purposeful availment of the jurisdiction.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an 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 specific modified-release formulation of the drug mirabegron.
  • Technical Context: The lawsuit concerns pharmaceutical formulation technology for oral solid dosage forms, specifically hydrogel-based systems designed to provide modified release of an active ingredient and reduce pharmacokinetic variability caused by food intake.
  • Key Procedural History: The complaint discloses that the patent-in-suit, U.S. Patent No. 10,842,780, was declared invalid in a separate litigation in the same district, Astellas Pharma Inc., et al. v. Sandoz Inc., et al., CA 20-1589 (D. Del.). That decision was issued on June 9, 2023, and Plaintiff filed an appeal to the Federal Circuit on June 12, 2023. Plaintiff asserts that it believes the invalidity decision will be reversed on appeal.

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 Mirabegron Bioequivalence Guidance
2020-11-24 U.S. Patent No. 10,842,780 issues
2023-05-18 Defendant MSN sends Paragraph IV certification notice letter to Plaintiff
2023-06-09 '780 Patent declared invalid in Astellas v. Sandoz (D. Del.)
2023-06-12 Plaintiff appeals the Sandoz invalidity decision to the Federal Circuit
2023-06-23 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.

The Invention Explained

  • Problem Addressed: The patent's background section describes clinical trial results for conventional, rapid-release formulations of the active ingredient mirabegron, which is depicted in the complaint by its chemical formula (Compl. ¶19). These trials revealed that pharmacokinetic data, 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" ('780 Patent, col. 6:50-54). This "food effect" is undesirable as it can lead to inconsistent drug performance.
  • The Patented Solution: The invention is a modified-release tablet designed to mitigate this food effect by controlling the drug's release over time. The solution involves combining mirabegron with two specific types of excipients: (1) a "hydrogel-forming polymer" (e.g., polyethylene oxide) and (2) a highly water-soluble "additive" (e.g., polyethylene glycol) that "ensures penetration of water into the pharmaceutical composition" ('780 Patent, Abstract; col. 7:1-15). This combination creates a matrix that swells into a hydrogel upon ingestion, slowing the drug's release so that it becomes the "rate-limiting step for absorption," thereby reducing the impact of food in the gastrointestinal tract ('780 Patent, col. 6:50-53).
  • Technical Importance: Developing oral drug formulations that minimize or eliminate the food effect is a significant objective in pharmaceutical science, as it improves a drug's predictability, safety, and patient compliance by removing the need to coordinate dosing with meals ('780 Patent, col. 6:26-29).

Key Claims at a Glance

  • The complaint asserts "one or more claims" without specifying them (Compl. ¶42). Independent claim 1 is representative of the core invention.
  • The essential elements of independent claim 1 include:
    • A pharmaceutical composition comprising 10 mg to 200 mg of mirabegron.
    • A "sustained release hydrogel-forming formulation" comprising a specific "hydrogel-forming polymer" (selected from a list including polyethylene oxide) with a defined average molecular weight.
    • An "additive" (selected from a list including polyethylene glycol) with a specified water solubility.
    • A specific in vitro drug dissolution profile: "39% or less after 1.5 hours, and at least 75% after 7 hours," when tested under defined USP paddle method conditions.

III. The Accused Instrumentality

Product Identification

  • Defendant's Abbreviated New Drug Application ("ANDA") No. 218543 for mirabegron extended-release tablets in 25 mg and 50 mg strengths (the "MSN ANDA Product") (Compl. ¶7).

Functionality and Market Context

  • The MSN ANDA Product is a proposed generic version of Plaintiff's Myrbetriq® extended-release tablets, which are used for the treatment of overactive bladder (Compl. ¶7, ¶20). The complaint alleges that by filing its ANDA, Defendant has represented to the FDA that its product has the same active ingredient, dosage form, and route of administration as Myrbetriq® and is bioequivalent to it (Compl. ¶39). The complaint's infringement theory rests on the allegation that to achieve the required bioequivalence with Myrbetriq® (the reference standard), the MSN ANDA Product must necessarily use a "hydrogel formulation" and exhibit dissolution properties that are the "same as or equivalent to" those of Myrbetriq®, which are alleged to be covered by the '780 Patent (Compl. ¶46-47). The complaint includes a table outlining the FDA's "Mirabegron Bioequivalence Guidance" for dissolution testing (Compl. ¶36).

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 The MSN ANDA Product is alleged to contain 25 mg or 50 mg of mirabegron, the same active ingredient as Myrbetriq®. ¶45 col. 8:46-52
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... The complaint alleges, on information and belief, that because of the dissolution requirements for bioequivalence, the MSN ANDA Product "uses a hydrogel formulation" and "contains a hydrogel-forming polymer." ¶46-48 col. 19:22-34
and an additive having a water solubility of at least 0.1 g/mL... wherein the additive is at least one selected from the group consisting of polyethylene glycol... The complaint alleges, on information and belief, that the MSN ANDA Product "contains... an additive that meet the claim limitations of one or more claims of the '780 Patent." ¶47-48 col. 19:25; 19:35-42
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 Plaintiff's own Myrbetriq® tablets meet this dissolution profile (¶23) and that to establish bioequivalence, the MSN ANDA Product will have "equivalent dissolution properties" and a "dissolution profile meeting the dissolution rate element of the claims" (¶46, 48). ¶48 col. 19:42-49
  • Identified Points of Contention:
    • Factual Question: The complaint's allegations regarding the specific composition of the MSN ANDA Product are made "on information and belief." A central question for discovery will be whether Defendant’s formulation in fact contains a "hydrogel-forming polymer" and an "additive" that fall within the definitions and Markush groups of Claim 1.
    • Scope Question: The infringement theory relies on an inferential chain: (1) Defendant's product must be bioequivalent to Myrbetriq®; (2) Myrbetriq® has a hydrogel formulation with a specific dissolution profile; (3) therefore, Defendant's product must have a formulation and profile that infringe the '780 patent. A key point of contention may be whether meeting FDA bioequivalence requirements necessarily proves infringement of each element of the asserted patent claims.
    • Technical Question: Does the dissolution profile of the MSN ANDA Product, when tested, actually meet the specific rates ("39% or less" at 1.5h, "at least 75%" at 7h) at the specific conditions ("200 rpm" paddle) required by the claim?

V. Key Claim Terms for Construction

  • The Term: "hydrogel-forming polymer"

    • Context and Importance: This term defines one of the two key excipients required by the invention. The infringement analysis will depend on whether the polymer used in the MSN ANDA Product falls within the scope of this term. Practitioners may focus on this term because the patent defines it by a list of polymer types (a Markush group), a broad range of molecular weights (100,000 to 8,000,000), and functional properties.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claim language "at least one compound selected from the group consisting of..." suggests the list is not merely exemplary but defines the scope ('780 Patent, col. 19:29-34). The specification provides extensive lists of suitable polymers with a wide range of properties, potentially supporting a broad reading of the polymer types included ('780 Patent, col. 9:43-col. 10:48).
      • Evidence for a Narrower Interpretation: A defendant may argue that the term should be limited by the specific examples detailed in the patent, or that the functional context—creating a hydrogel that controls release to a specific dissolution profile—narrows its scope to only those polymers capable of achieving that precise outcome ('780 Patent, Examples 1-17).

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

    • Context and Importance: This term defines the second key excipient, which "ensures penetration of water into the" formulation. Its construction is critical as it is defined by both a functional role and a specific, quantitative physical property (solubility).
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claim provides a broad Markush group of potential additives, including polymers, sugar alcohols, saccharides, surfactants, salts, and amino acids ('780 Patent, col. 19:35-42). This suggests the term is intended to cover a wide variety of chemical classes, so long as the solubility requirement is met.
      • Evidence for a Narrower Interpretation: The specification explains the additive's purpose is to "ensure[] penetration of water into the pharmaceutical composition" ('780 Patent, col. 7:11-12). A defendant could argue that an accused excipient, even if it meets the solubility and Markush group requirements, does not infringe if it does not perform this specific function in the accused formulation.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both contributory and induced infringement.
    • Contributory Infringement (Count II): The complaint alleges the MSN ANDA Product is a material part of the patented invention and has no substantial non-infringing uses, and that Defendant knows this (Compl. ¶53-54).
    • Induced Infringement (Count III): The complaint alleges Defendant has knowledge of the '780 Patent and specifically intends to cause infringement by marketing and selling its ANDA product for administration to patients, which would constitute direct infringement (Compl. ¶61-64).
  • Willful Infringement: The complaint does not contain a separate count for willful infringement but does request a declaration that the case is "exceptional" and an award of attorney fees, which is often associated with findings of willfulness or other litigation misconduct (Compl., Prayer for Relief ¶F). The allegations of knowledge for the indirect infringement claims could potentially form the basis for a future willfulness claim.

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

  1. Impact of Prior Invalidation: A threshold issue is the legal effect of the June 9, 2023 judgment in the Sandoz case declaring the '780 patent invalid. The court must decide whether to stay this case pending the Federal Circuit's review of that decision or to proceed, raising the possibility of collateral estoppel or conflicting judgments.
  2. The Factual Link to Infringement: A central evidentiary question will be one of compositional identity: does the specific formulation detailed in Defendant's confidential ANDA submission actually contain excipients that fall within the scope of the "hydrogel-forming polymer" and "additive" limitations of the asserted claims? The plaintiff's case is built on the inference that bioequivalence requires such a formulation.
  3. The Functional Link to Infringement: The case may also turn on a question of functional proof: assuming the accused product's composition is similar, does its performance match the patent's specific dissolution rate limitations? The dispute will likely focus on whether meeting FDA bioequivalence standards is sufficient proof of infringement of the patent's distinct, numerically-defined functional requirements.