DCT

1:20-cv-01589

Astellas Pharma Inc v. Sandoz Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:20-cv-01589, D. Del., 11/24/2020
  • Venue Allegations: Venue is asserted based on Defendants' incorporation in Delaware, their continuous and systematic contacts with the state, or their status as foreign defendants not subject to jurisdiction in any other single state's courts.
  • Core Dispute: Plaintiff alleges that Defendants' filing of Abbreviated New Drug Applications (ANDAs) seeking to market generic versions of Plaintiff's overactive bladder drug Myrbetriq® constitutes an act of infringement of a patent covering a specific modified-release formulation.
  • Technical Context: The technology concerns pharmaceutical formulations for mirabegron, designed to provide sustained release while mitigating the "food effect"—variability in drug absorption when taken with or without food.
  • Key Procedural History: The complaint notes that Plaintiff previously sued the same group of Defendants for infringing other Orange Book-listed patents covering Myrbetriq®. Those cases, which did not involve the patent-in-suit as it had not yet issued, were resolved by settlement. This history establishes the Defendants' long-standing awareness of Plaintiff's intellectual property surrounding the Myrbetriq® product.

Case Timeline

Date Event
2008-09-30 U.S. Patent 10,842,780 Priority Date
2012-06-28 FDA approves New Drug Application for Myrbetriq®
2013-06-20 FDA issues notice regarding Mirabegron Bioequivalence Guidance
2016-08-24 Earliest Defendant Notice Letter date mentioned (Actavis)
2020-11-24 U.S. Patent 10,842,780 Issues
2020-11-24 Complaint Filed

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

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

The Invention Explained

  • Problem Addressed: The patent's background section explains that conventional, rapid-release formulations of the active ingredient, mirabegron, exhibit a significant "food effect," where key pharmacokinetic parameters such as maximum plasma concentration (Cmax) and total drug exposure (AUC) vary unpredictably depending on whether the drug is taken in a "fasted state" or a "fed state" (’780 Patent, col. 1:50-62). This variability is a clinical disadvantage.
  • The Patented Solution: The invention claims a modified-release pharmaceutical composition that controls the release of mirabegron over time to reduce this food effect. The patented solution involves combining the active ingredient with a "hydrogel-forming polymer" and a specific type of highly water-soluble "additive" that "ensures penetration of water into the" tablet ('780 Patent, col. 2:20-30; Abstract). This formulation is designed to make the drug's release from the tablet, rather than gastrointestinal conditions, the rate-limiting step for absorption, thereby creating a more consistent drug concentration profile regardless of food intake ('780 Patent, col. 2:40-53).
  • Technical Importance: Developing a formulation that minimizes the food effect enhances therapeutic predictability and patient convenience for a daily-use medication.

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the '780 patent; independent claim 1 is representative ('780 Patent, col. 19:20-col. 20:49).
  • The essential elements of independent claim 1 are:
    • A pharmaceutical composition comprising 10 mg to 200 mg of mirabegron or its salt.
    • The composition is a "sustained release hydrogel-forming formulation" that includes:
      • A "hydrogel-forming polymer" with a specific molecular weight (100,000 to 8,000,000) selected from a defined class of polymers (e.g., polyethylene oxide, HPMC).
      • An "additive" with a high water solubility (at least 0.1 g/mL) selected from a defined class of substances (e.g., polyethylene glycol, mannitol).
    • The composition exhibits a specific in vitro 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 implicitly reserves the right to assert other claims, including dependent claims.

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are the proposed generic mirabegron extended-release tablets (25 mg and 50 mg) described in the Abbreviated New Drug Applications (ANDAs) filed by each Defendant with the FDA (Compl. ¶¶118, 122).

Functionality and Market Context

  • The Defendants' products are intended to be generic substitutes for Plaintiff's branded Myrbetriq® tablets (Compl. ¶¶118-119). To gain FDA approval, these generic products must demonstrate bioequivalence to Myrbetriq® (Compl. ¶118).
  • The complaint alleges that achieving this bioequivalence requires filers to follow the FDA's "Mirabegron Bioequivalence Guidance" (Compl. ¶123). The complaint includes a table summarizing the FDA's recommended dissolution testing method to establish bioequivalence (Compl. ¶115). This visual, a table titled "Mirabegron Bioequivalence Guidance," specifies the required USP apparatus, speed, medium, and sampling times for the test (Compl. ¶115).
  • Plaintiff alleges that Myrbetriq® itself meets the dissolution profile claimed in the '780 patent (Compl. ¶104). The complaint's infringement theory is built on the premise that for the Defendants' products to be bioequivalent, they must also have "equivalent dissolution properties" and use a "hydrogel formulation, the same as or equivalent to the Myrbetriq® Tablets formulation," which is allegedly covered by the '780 patent (Compl. ¶123).

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart. The infringement theory is based on the assertion that meeting the FDA's bioequivalence requirements for Myrbetriq® necessitates the use of a formulation that infringes the '780 patent.

U.S. Patent No. 10,842,780 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]...or a pharmaceutically acceptable salt thereof Defendants' ANDA products contain 25 mg or 50 mg of mirabegron in extended-release tablets. ¶122 col. 19:20-24
in a sustained release hydrogel-forming formulation comprising a hydrogel-forming polymer...and an additive... It is alleged that to be bioequivalent to Myrbetriq®, which uses a hydrogel, the ANDA product must use a "hydrogel formulation, the same as or equivalent to the Myrbetriq® Tablets formulation." ¶123 col. 19:25-30
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...[a specific USP test]... It is alleged that the ANDA product must have "equivalent dissolution properties" to Myrbetriq®, which itself is alleged to meet the claimed dissolution profile. ¶¶104, 123 col. 20:42-49

Identified Points of Contention

  • Scope Questions: A central dispute will be whether demonstrating "bioequivalence" to Myrbetriq® necessarily requires an infringing formulation. Defendants may argue that it is possible to formulate a generic product that is bioequivalent but uses different excipients or mechanisms that fall outside the literal scope of the asserted claims.
  • Technical Questions: The complaint's allegations regarding the composition of the accused products are based on "information and belief" derived from regulatory requirements (Compl. ¶123). A key factual question is what the ANDA filings reveal about the actual excipients and formulation technology used in each Defendant's product. Infringement will depend on whether those specific components meet the claim limitations for the "hydrogel-forming polymer" and the highly soluble "additive."

V. Key Claim Terms for Construction

"hydrogel-forming formulation"

  • Context and Importance: The core of the infringement allegation is that the Defendants' products must be a "hydrogel-forming formulation" to be bioequivalent to Myrbetriq®. The definition of this term will be critical to determining if the accused products, once their composition is known, fall within the claim scope.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent provides a list of specific polymers that are considered "hydrogel-forming," such as polyethylene oxide and hydroxypropyl methylcellulose ('780 Patent, col. 7:41-49). Plaintiff may argue that a formulation containing one of these specified polymers at a sufficient concentration is, by definition, a "hydrogel-forming formulation."
    • Evidence for a Narrower Interpretation: The patent describes the function of the formulation is to control the drug release rate to reduce food effects ('780 Patent, col. 2:40-53). A defendant might argue that "hydrogel-forming formulation" is not merely structural but requires the formulation to achieve this specific functional outcome in a particular way, potentially limiting the term to the embodiments and examples disclosed.

The dissolution rate profile defined in the "wherein" clause ("wherein a drug dissolution rate...is 39% or less after 1.5 hours...")

  • Context and Importance: This functional limitation is the measurable benchmark of the invention. Practitioners may focus on this term because its treatment as either a hard limitation or a mere statement of intended result will significantly impact the infringement analysis.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation (treating it as a limitation): Plaintiff's case relies on this clause being a dispositive test. They allege Myrbetriq® meets this profile and that bioequivalent generics must as well (Compl. ¶¶104, 123). Courts often treat "wherein" clauses that state the condition of the invention as limitations.
    • Evidence for a Narrower Interpretation (treating it as an intended result): A defendant could argue that this clause only describes the performance of a composition that is already defined by its structural elements (the specific polymer and additive). Under this view, a product that meets the dissolution profile but lacks the required structural components would not infringe.

VI. Other Allegations

Indirect Infringement

The primary allegation is infringement under 35 U.S.C. § 271(e)(2), which defines the submission of an ANDA for a patented drug as a technical act of infringement to create jurisdiction for the lawsuit before a commercial launch occurs (Compl. ¶120). The complaint also seeks a declaration that future commercial manufacture and sale will constitute infringement under 35 U.S.C. § 271(a) (Compl. ¶124).

Willful Infringement

The complaint does not explicitly allege "willful infringement." However, it seeks a declaration that the case is "exceptional" and an award of attorney fees pursuant to 35 U.S.C. § 285 (Compl. p. 41, ¶F). The extensive history of prior litigation between the parties over the same drug product may be used by Plaintiff to argue that Defendants' conduct was egregious, potentially supporting an exceptional case finding.

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

  • A core issue will be one of "inferential proof": Can Plaintiff establish that the FDA's bioequivalence requirements are so stringent that any generic version of Myrbetriq® must necessarily practice the patented combination of a specific hydrogel polymer, a highly soluble additive, and the claimed dissolution profile?
  • A key evidentiary question will be one of "composition": Does discovery of the Defendants' confidential ANDA submissions reveal formulations that fall within the literal scope of the '780 patent’s claims, or have Defendants engineered non-infringing formulations that still achieve bioequivalence?
  • A central legal question will be one of "claim scope": Will the court construe the "hydrogel-forming formulation" limitation broadly to cover any formulation using a listed polymer, and will it treat the dissolution rate "wherein" clause as a dispositive test for infringement, or will it adopt narrower interpretations that could provide Defendants a path to non-infringement?