Astellas Ireland Co Ltd v. Prinston Pharmaceutical Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Astellas Pharma Inc. (Japan), Astellas Ireland Co., Ltd. (Ireland), and Astellas Pharma Global Development, Inc. (Delaware)
  • Defendant: Prinston Pharmaceutical Inc. (Delaware), Zhejiang Huahai Pharmaceutical Co., Ltd. (China), Huahai US Inc. (New Jersey), and Solco Healthcare US LLC (Delaware)
  • Plaintiff’s Counsel: McCarter & English, LLP
• Case Identification: 1:21-cv-01771, D. Del., 12/17/2021
• Venue Allegations: Venue is alleged to be proper in the District of Delaware based on the Delaware incorporation of Prinston Pharmaceutical Inc. and Solco Healthcare US LLC, and because the foreign defendants have sufficient contacts with the United States as a whole.
• Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the drug Myrbetriq® constitutes an act of infringement of a patent covering a modified-release pharmaceutical formulation.
• Technical Context: The technology concerns oral drug delivery formulations designed to provide sustained release of an active ingredient and to mitigate the "food effect," where the presence or absence of food affects drug absorption and efficacy.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' notification to Plaintiff of their ANDA filing, which included a Paragraph IV certification asserting that the patent-in-suit is invalid, unenforceable, or will not be infringed by the proposed generic product. The complaint was filed within the 45-day statutory window, which typically triggers a 30-month stay of FDA approval for the generic drug.

Case Timeline

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 ('780 Patent). (Compl. ¶25).

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

The Invention Explained

• Problem Addressed: The patent describes that conventional formulations of the active ingredient, mirabegron, exhibit a significant "food effect," meaning that key pharmacokinetic parameters like maximum plasma concentration (Cmax) and total drug exposure (AUC) vary substantially depending on whether the drug is taken with food or in a fasted state ('780 Patent, col. 1:50-58). This variability can lead to inconsistent therapeutic effects.
• The Patented Solution: The invention is a modified-release pharmaceutical composition that reduces this food effect by controlling the drug's release rate. This is achieved by combining the active ingredient with two key types of additives: (1) a "hydrogel-forming polymer" (e.g., polyethylene oxide) that swells to control drug release over time, and (2) a highly water-soluble "additive" (e.g., polyethylene glycol) that "ensures penetration of water into the pharmaceutical composition," facilitating the hydrogel's formation ('780 Patent, col. 2:17-30; Abstract).
• Technical Importance: Formulations that minimize or eliminate the food effect provide more predictable and reliable drug absorption, which can improve safety and efficacy and offer greater convenience for patients who do not need to time doses relative to meals ('780 Patent, col. 2:50-62).

Key Claims at a Glance

• The complaint alleges infringement of "one or more claims" of the '780 Patent without specifying particular claims (Compl. ¶41). The patent’s independent claims define the broadest scope of the invention.
• Independent Claim 1 recites a pharmaceutical composition comprising:
  • 10 mg to 200 mg of mirabegron;
  • A hydrogel-forming polymer from a specific list with a defined molecular weight (100,000 to 8,000,000);
  • An additive with a specific water solubility (at least 0.1 g/mL); and
  • A specific, two-part drug dissolution rate profile when measured under defined conditions (a paddle rotation speed of 200 rpm).
• Independent Claim 22 recites a pharmaceutical composition comprising:
  • 10 mg to 200 mg of mirabegron;
  • A "means for forming a hydrogel";
  • A "means for ensuring penetration of water into the pharmaceutical composition"; and
  • The same specific drug dissolution rate profile as in claim 1.

III. The Accused Instrumentality

Product Identification

• Defendants' proposed generic mirabegron extended-release tablets in 25 mg and 50 mg strengths, as described in ANDA No. 209475 ("Prinston's ANDA Product") (Compl. ¶9). The complaint includes a depiction of the chemical formula for mirabegron (Compl. ¶20).

Functionality and Market Context

• The accused product is a generic version of Astellas's Myrbetriq® extended-release tablets, which are indicated for the treatment of overactive bladder (Compl. ¶9, ¶21).
• As a generic drug submitted for approval via an ANDA, the product must have the same active ingredient, dosage form, and strength as Myrbetriq®, and it must be bioequivalent to Myrbetriq®, which serves as the Reference Listed Drug (Compl. ¶36).
• The complaint alleges that to establish bioequivalence, the accused product must have "equivalent dissolution properties" to Myrbetriq® and, on information and belief, must use a "hydrogel formulation, the same as or equivalent to the Myrbetriq® Tablets formulation" (Compl. ¶38).

IV. Analysis of Infringement Allegations

The complaint's infringement theory is based on the statutory act of filing an ANDA under 35 U.S.C. § 271(e)(2)(A). It alleges that the product described in the ANDA, if approved and marketed, would infringe the ’780 Patent. The allegations for the means-plus-function limitations of claim 22 are summarized below.

'780 Patent Infringement Allegations

Identified Points of Contention

• Technical Question: A primary dispute may arise from the specific dissolution rate limitation. The patent claims require a profile measured at a "paddle rotation speed of 200 rpm" ('780 Patent, cl. 1, 22). However, the complaint references FDA's bioequivalence guidance, which specifies testing with "USP Apparatus I (Basket)" at "100 RPMs" (Compl. ¶33), and also alleges the Myrbetriq® tablets' dissolution profile is measured using "USP II Method" at 200 rpm (Compl. ¶24). This raises the question of whether the accused product, which must satisfy regulatory requirements under one set of test conditions, can be proven to also meet the different conditions recited in the patent claims.
• Scope Questions: For the means-plus-function elements of claim 22, infringement will depend on whether the excipients used in the accused product are structurally equivalent to the "hydrogel-forming polymers" and "hydrophilic bases" disclosed in the patent's specification. The complaint's allegation rests on an inference based on the regulatory requirement for bioequivalence, raising the question of what evidence exists within the ANDA to demonstrate this structural correspondence.

V. Key Claim Terms for Construction

• The Term: "a means for ensuring penetration of water into the pharmaceutical composition"
• Context and Importance: This is a means-plus-function limitation governed by 35 U.S.C. § 112(f), meaning its scope is limited to the structures disclosed in the specification that perform the stated function, and their equivalents. Practitioners may focus on this term because infringement depends on whether the defendant's formulation, detailed in its confidential ANDA, contains excipients that are structurally equivalent to those disclosed in the patent. The plaintiff's theory of an "equivalent" formulation (Compl. ¶38) directly invokes this analysis.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The patent specification discloses a wide variety of corresponding structures, referred to as "hydrophilic bases." This includes not only specific chemicals like polyethylene glycol but also broad classes of substances such as "sugar alcohols," "saccharides," "surfactants," "salts," and "amino acids" ('780 Patent, col. 10:16-34). A plaintiff may argue this disclosure supports a broad range of structural equivalents.
  • Evidence for a Narrower Interpretation: A defendant may argue that the numerous working examples in the patent consistently use polyethylene glycol (PEG) as the hydrophilic base ('780 Patent, col. 13-14, Examples 1-17). This emphasis on PEG could be used to argue for a narrower construction of the scope of equivalents.

VI. Other Allegations

• Indirect Infringement: The complaint is premised on the act of filing the ANDA as a statutory act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶41). It does not plead separate counts for induced or contributory infringement.
• Willful Infringement: The complaint does not contain an explicit allegation of willful infringement.

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

• A key evidentiary question will be one of functional proof: Can the plaintiff demonstrate that the defendant's proposed generic product—which is evaluated for regulatory bioequivalence under specific FDA-guided testing parameters—would also meet the precise, two-part dissolution rate profile required by the patent claims, which specifies a different testing methodology (i.e., a paddle rotation speed of 200 rpm)?
• A core issue will be one of structural correspondence under § 112(f): Does the formulation detailed in the defendant’s confidential ANDA contain excipients that are structurally the same as, or equivalent to, the specific "hydrophilic bases" and "hydrogel-forming polymers" disclosed in the '780 Patent specification as the means for performing the claimed functions? The outcome may depend on a comparison of the undisclosed generic formula to the patent's disclosed embodiments.