DCT

1:21-cv-00664

Astellas Pharma v. Sandoz

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:21-cv-00664, D. Del., 05/07/2021
  • Venue Allegations: Venue is asserted based on Defendant Sandoz Inc. being incorporated in the State of Delaware and having previously availed itself of the jurisdiction of the Delaware federal court in related litigation.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's Myrbetriq® extended-release tablets constitutes an act of infringement of a patent covering a modified-release pharmaceutical formulation.
  • Technical Context: The technology concerns oral drug delivery systems designed to create a "modified release" profile, specifically to mitigate the "food effect," where drug absorption rates vary depending on a patient's food intake.
  • Key Procedural History: This action was filed under the Hatch-Waxman Act, triggered by Defendant's submission of an ANDA with a Paragraph IV certification asserting that Plaintiff's patent is invalid, unenforceable, or will not be infringed. The complaint notes prior related litigation between the parties concerning Myrbetriq®.

Case Timeline

Date Event
2008-09-30 Earliest Priority Date for ’780 Patent
2012-06-28 FDA Approval of Myrbetriq® New Drug Application
2013-06-20 FDA Issues Notice Regarding Bioequivalence Guidance for Mirabegron
2020-11-24 U.S. Patent No. 10,842,780 Issues
2021-03-25 Sandoz Sends Notice Letter to Astellas Regarding ANDA Filing
2021-05-07 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 trials of conventional formulations of the active ingredient, mirabegron, which revealed that pharmacokinetic data "unexpectedly varied according to the presence or absence of the intake of food" ('780 Patent, col. 1:50-54). This "food effect" could lead to inconsistent drug levels in patients, creating challenges for predictable dosing and efficacy ('780 Patent, col. 1:54-62).
  • The Patented Solution: The invention claims to solve this problem with a modified-release formulation that combines the active drug with two other components: a "hydrogel-forming polymer" and a highly water-soluble "additive" ('780 Patent, Abstract). This combination is designed to form a hydrogel matrix that controls the rate at which the drug is released from the tablet, thereby reducing the impact of food intake on the drug's absorption profile and making its pharmacokinetics more consistent ('780 Patent, col. 2:20-30).
  • Technical Importance: Developing formulations that mitigate or eliminate food effects is significant in pharmacology because it can lead to more reliable drug performance and simplify patient instructions, removing the need to time doses relative to meals ('780 Patent, col. 2:25-28).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" of the ’780 Patent (Compl. ¶33). 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 or its salt ('780 Patent, col. 19:20-24).
    • The composition is a "sustained release hydrogel-forming formulation" containing a "hydrogel-forming polymer" with a specified average molecular weight (100,000 to 8,000,000) ('780 Patent, col. 19:24-26).
    • The formulation also contains an "additive" with a specified high water solubility (at least 0.1 g/mL) ('780 Patent, col. 20:25-27).
    • The "hydrogel-forming polymer" is selected from a specific list, including polyethylene oxide and hydroxypropyl methylcellulose ('780 Patent, col. 20:28-35).
    • The "additive" is selected from a specific list, including polyethylene glycol and D-mannitol ('780 Patent, col. 20:35-42).
    • The composition exhibits a specific drug dissolution rate: 39% or less after 1.5 hours and at least 75% after 7 hours, when measured under precise test conditions (USP Apparatus II, 900 mL of pH 6.8 buffer, 200 rpm paddle speed) ('780 Patent, col. 20:37-46).
  • The complaint does not specify any dependent claims but reserves the right to assert them.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Sandoz’s proposed generic mirabegron extended-release tablets (25 mg and 50 mg strengths), as described in its Abbreviated New Drug Application (ANDA) No. 209441 submitted to the FDA (Compl. ¶6).

Functionality and Market Context

The complaint alleges that Sandoz’s ANDA seeks approval to market a generic version of Astellas’s Myrbetriq® tablets for the treatment of overactive bladder (Compl. ¶6, ¶16). To obtain FDA approval, the Sandoz product must be bioequivalent to Myrbetriq® (Compl. ¶31). The complaint asserts that achieving this bioequivalence requires the Sandoz product to have "equivalent dissolution properties" to Myrbetriq® and, by extension, to use a hydrogel formulation that is the "same as or equivalent to" the formulation of the branded drug (Compl. ¶29, ¶33). The complaint includes a depiction of the chemical formula for mirabegron, the active ingredient in both the branded and accused products (Compl. ¶15).

IV. Analysis of Infringement Allegations

The complaint’s infringement theory is based on the premise that for Sandoz's ANDA product to be approved as bioequivalent, it must necessarily practice the claimed invention.

’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 [mirabegron]... Sandoz’s ANDA Product contains the active ingredient mirabegron in 25 mg and 50 mg strengths, which falls within the claimed range. ¶6, ¶31 col. 6:46-51
...in a sustained release hydrogel-forming formulation comprising a hydrogel-forming polymer... and an additive... The complaint alleges that to be bioequivalent to Myrbetriq® Tablets, the Sandoz ANDA Product "uses a hydrogel formulation, the same as or equivalent to the Myrbetriq® Tablets formulation." ¶33 col. 7:16-20
...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 Sandoz's product "will have equivalent dissolution properties" to Myrbetriq® Tablets. It separately alleges that Myrbetriq® Tablets meet this claimed dissolution profile. The complaint includes a table from the FDA's "Mirabegron Bioequivalence Guidance" outlining dissolution requirements for ANDA filers. ¶19, ¶28, ¶33 col. 20:37-46

Identified Points of Contention

  • Evidentiary Question: The complaint's infringement theory appears to rest on an inference: because Sandoz's product must be bioequivalent to Myrbetriq®, it must therefore have the same formulation and dissolution properties claimed in the patent. The central question for the court will be whether the information contained within Sandoz's confidential ANDA submission actually describes a product that meets every limitation of Claim 1, or if bioequivalence could be achieved via a different, non-infringing formulation or mechanism.
  • Technical Question: The complaint cites both the dissolution profile of Myrbetriq® under the conditions specified in the patent (USP Apparatus II, 200 rpm) and the FDA's guidance for ANDA filers, which specifies different test conditions (USP Apparatus I, 100 rpm) (Compl. ¶19, ¶28). A potential point of dispute is whether meeting bioequivalence requirements under the FDA's test parameters necessarily proves that the Sandoz product will also meet the specific dissolution profile claimed in the patent under its different test parameters.

V. Key Claim Terms for Construction

The Term: "hydrogel-forming polymer"

  • Context and Importance: The complaint's infringement theory relies on the allegation that Sandoz's product uses a "hydrogel formulation" (Compl. ¶33). The definition of this term is foundational to the infringement analysis. Practitioners may focus on whether the excipients in the Sandoz product fall within the patent's definition of this term.
  • Intrinsic Evidence for a Broader Interpretation: Claim 1 provides a specific, though closed, list of qualifying polymers, such as "polyethylene oxide, hydroxypropyl methylcellulose, [and] hydroxypropyl cellulose," which could be argued to define the full scope of the term ('780 Patent, col. 20:31-35).
  • Intrinsic Evidence for a Narrower Interpretation: The specification provides detailed examples of these polymers, including specific commercial grades, molecular weights, and viscosity ranges (e.g., "Polyox WSR-308 [average molecular weight: 8,000,000...") ('780 Patent, col. 8:50-53). A party could argue that the term should be limited to polymers exhibiting these exemplified characteristics.

The Term: "an additive"

  • Context and Importance: Claim 1 requires the presence of both a "hydrogel-forming polymer" and a distinct "additive." Infringement requires the accused product to contain separate components corresponding to each of these limitations. A key question will be whether the excipients in the Sandoz formulation map onto this two-component requirement.
  • Intrinsic Evidence for a Broader Interpretation: The specification refers to the additive as a "hydrophilic base" and provides a long list of suitable substances, including various PEGs, sugar alcohols, and salts ('780 Patent, col. 10:16-34).
  • Intrinsic Evidence for a Narrower Interpretation: The claim requires the additive to have a specific functional property: "a water solubility of at least 0.1 g/mL at 20±5° C." ('780 Patent, col. 20:25-27). This functional requirement limits the scope of the term to only those substances that meet the specified solubility threshold.

VI. Other Allegations

Indirect Infringement

The action is brought under 35 U.S.C. § 271(e)(2), which defines the submission of an ANDA for a drug claimed in a patent as a statutory act of infringement. The complaint does not plead separate counts for inducement or contributory infringement, as the filing of the ANDA itself provides the cause of action.

Willful Infringement

The complaint does not use the term "willful infringement" but requests a declaration that the case is "exceptional" and an award of attorneys' fees under 35 U.S.C. § 285 (Compl., Prayer for Relief ¶F). The factual basis for this appears to be Sandoz's alleged pre-suit knowledge of the ’780 Patent, evidenced by its Paragraph IV certification and the formal notice letter sent to Astellas on March 25, 2021 (Compl. ¶6-7).

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

  • A core issue will be one of proof by inference: Can Astellas establish that Sandoz’s product will infringe based on the regulatory requirement of bioequivalence, or will it be required to obtain and rely on the specific formulation details from Sandoz's confidential ANDA to prove that the accused product meets every limitation of the asserted claims?
  • A key technical and legal question will be the correlation of testing standards: Does demonstrating that Sandoz's product meets the FDA's bioequivalence dissolution requirements (under USP Apparatus I, 100 RPM) legally and factually compel the conclusion that it also satisfies the patent's distinct dissolution claim limitation (under USP Apparatus II, 200 RPM)? The outcome may depend on expert testimony regarding the relationship between these two testing methodologies.