DCT

1:24-cv-00939

Astellas Pharma Inc v. Lupin Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00939, D. Del., 11/04/2024
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware based on Defendant Lupin Pharmaceuticals, Inc.'s incorporation in the state, and because both defendants are alleged to conduct systematic and continuous business in Delaware, including the sale of the accused products.
  • Core Dispute: Plaintiff alleges that Defendant’s generic mirabegron extended-release tablets, approved under Abbreviated New Drug Application (ANDA) No. 209485, infringe a patent related to a specific modified-release pharmaceutical formulation.
  • Technical Context: The technology concerns oral drug delivery formulations for mirabegron, an active ingredient used to treat overactive bladder, designed to control the drug's release profile to mitigate inconsistent absorption caused by food intake.
  • Key Procedural History: The asserted U.S. Patent No. 12,059,409 is a continuation of the application that led to U.S. Patent No. 10,842,780, which is the subject of separate, ongoing litigation between the same parties. The complaint notes that in the prior litigation, the Defendant stipulated to infringing all limitations of the asserted claims of the '780 patent except for a specific dissolution rate limitation. The complaint alleges the dissolution rate limitation in the newly asserted '409 patent is identical to the one disputed in the ongoing case, suggesting the dispute will center on this single claim element.

Case Timeline

Date Event
2008-09-30 '409 Patent Priority Date (Provisional App. 61/101,338)
2016-08-25 Lupin sends first notice letter regarding its ANDA filing
2020-11-24 U.S. Patent No. 10,842,780 (parent to '409 patent) issues
2021-02-08 Lupin sends second notice letter regarding its ANDA
2022-09-28 Lupin receives final FDA approval for its ANDA Products
2024-04-19 Lupin commercially launches 25 mg generic mirabegron tablet
2024-08-13 U.S. Patent No. 12,059,409 issues
2024-09-03 Lupin commercially launches 50 mg generic mirabegron tablet
2024-11-04 Complaint Filing Date

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

U.S. Patent No. 12,059,409 - "Pharmaceutical Composition for Modified Release"

  • Patent Identification: U.S. Patent No. 12,059,409, "Pharmaceutical Composition for Modified Release", issued August 13, 2024 (’409 Patent).

The Invention Explained

  • Problem Addressed: The patent's background section describes clinical findings where conventional, rapid-release formulations of the active ingredient mirabegron exhibited significant pharmacokinetic variability depending on whether the patient took the drug with food. Specifically, food intake was found to substantially decrease the maximum plasma concentration (Cmax) and the total drug exposure (AUC), leading to unpredictable therapeutic effects. ('409 Patent, col. 1:53-65).
  • The Patented Solution: The invention is a modified-release tablet that uses a hydrogel-forming formulation to control the drug's release over an extended period. By combining a hydrogel-forming polymer (polyethylene oxide) with a highly water-soluble additive (polyethylene glycol), the tablet is designed to make drug dissolution from the dosage form the rate-limiting step for absorption, rather than gastrointestinal transit time. This controlled release profile is intended to reduce the "food effect" and provide more consistent drug plasma levels regardless of meals. ('409 Patent, col. 2:47-65, col. 6:1-12).
  • Technical Importance: Developing an oral dosage form that minimizes food-effect variability is a significant objective in pharmaceutical science, as it can lead to more reliable dosing, better patient compliance, and more predictable clinical outcomes. ('409 Patent, col. 1:61-65).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent Claim 1. (Compl. ¶48).
  • The essential elements of Claim 1 are:
    • A tablet comprising 10 mg to 200 mg of mirabegron or a salt thereof.
    • The tablet is a sustained release hydrogel-forming formulation.
    • The formulation comprises a hydrogel-forming polymer (polyethylene oxide) with an average molecular weight of 200,000 to 7,000,000.
    • The formulation comprises an additive (polyethylene glycol) with a water solubility of at least 0.1 g/mL.
    • The tablet has a specific drug dissolution rate: 39% or less release after 1.5 hours, and at least 75% release after 7 hours, under specified USP test conditions.
  • The complaint does not explicitly reserve the right to assert other claims, but standard practice allows for amending such contentions.

III. The Accused Instrumentality

Product Identification

The accused products are Lupin's 25 mg and 50 mg Mirabegron Extended-Release Tablets, which are the generic versions of Astellas's Myrbetriq® tablets, marketed pursuant to ANDA No. 209485. (Compl. ¶¶6, 10). The complaint includes a visual representation of the chemical structure of mirabegron, the active ingredient in both the brand and generic products (Compl. p. 7).

Functionality and Market Context

The accused products are oral tablets indicated for the treatment of overactive bladder. (Compl. ¶25). They are formulated as sustained-release, hydrogel-forming compositions that contain polyethylene oxide and polyethylene glycol as inactive ingredients. (Compl. ¶¶51, 54). The complaint alleges that Lupin has represented to the FDA that its products are bioequivalent and therapeutically equivalent to the reference listed drug, Myrbetriq®. (Compl. ¶50). Lupin commercially launched its products in the U.S. in 2024, positioning them as lower-cost generic alternatives to the brand-name drug. (Compl. ¶¶33-34).

IV. Analysis of Infringement Allegations

The complaint’s infringement theory relies heavily on stipulations made by Lupin in a prior case involving the parent '780 patent, combined with new laboratory testing of Lupin’s commercially launched products to meet the final disputed limitation. (Compl. ¶¶31, 51-52, 64-65). The complaint also references a table from the FDA's "Mirabegron Bioequivalence Guidance," which specifies dissolution testing requirements for generic applicants (Compl. p. 12). This table provides context for the testing conditions recited in the patent claim and allegedly used by Lupin.

'409 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A tablet comprising 10 mg to 200 mg of [mirabegron], or a pharmaceutically acceptable salt thereof... The accused products are tablets containing either 25 mg or 50 mg of mirabegron. ¶53 col. 23:35-43
...in a sustained release hydrogel-forming formulation... The complaint cites a stipulation from prior litigation in which Lupin allegedly admitted its products "are sustained-release hydrogel-forming pharmaceutical compositions." ¶51 col. 23:39-40
...comprising a hydrogel-forming polymer having an average molecular weight of 200,000 to 7,000,000... The accused products allegedly use a grade of polyethylene oxide with an average molecular weight of 1,000,000, which falls within the claimed range. ¶56 col. 23:40-41
...and an additive having a water solubility of at least 0.1 g/mL at 20±5 °C... The accused products allegedly contain polyethylene glycol 6000 (PEG 6000) as an additive, which is alleged to have the required water solubility based on a prior stipulation. ¶57 col. 23:41-43
...wherein the hydrogel-forming polymer is polyethylene oxide... The accused products are alleged to contain polyethylene oxide which functions as the hydrogel-forming polymer. ¶¶54-55 col. 23:44-45
...wherein the additive is polyethylene glycol... The accused products are alleged to contain polyethylene glycol which functions as the additive. ¶¶54-55 col. 23:46-47
...wherein a drug dissolution rate from the tablet 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 laboratory testing performed on samples from Lupin’s commercial launches of both the 25 mg and 50 mg products confirmed that they meet this two-point dissolution profile under the specified conditions. ¶¶64-65 col. 23:48-54

Identified Points of Contention

  • Technical Question: The complaint's allegations regarding the dissolution rate are based on tests of "samples" from the commercial launches. (Compl. ¶¶64-65). This raises the evidentiary question of whether these samples are representative of all manufactured batches of Lupin's products. The central technical dispute may be one of consistency: does Lupin's manufacturing process ensure that its generic tablets reliably and consistently meet the specific two-point dissolution profile required by Claim 1, or can Lupin demonstrate meaningful variability that places some or all of its product outside the claim scope?

V. Key Claim Terms for Construction

  • The Term: "wherein a drug dissolution rate from the tablet 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"
  • Context and Importance: This functional limitation is the core of the asserted claim and the likely focal point of the infringement dispute. The complaint's structure, which leverages prior litigation stipulations to dispense with all other claim elements, underscores the centrality of this term. (Compl. ¶31). Practitioners may focus on this term because its satisfaction appears to be the only contested issue for infringement, and its interpretation will determine whether the accused products, which are otherwise admitted to be very similar, fall inside or outside the claim.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party arguing for a straightforward application of the term would point to the plain language of the claim, which sets out a clear, functional test with specific, objective parameters (time points, percentages, buffer, pH, rotation speed). The patent specification describes this profile as a means to an end—reducing food effects—but does not appear to limit the claim to any particular method of achieving it beyond the recited composition. ('409 Patent, col. 6:13-22).
    • Evidence for a Narrower Interpretation: A party seeking to narrow the term might argue that the claim should be understood in the context of the specific embodiments that achieve this result. For example, the patent discloses specific formulations in its Examples (e.g., Examples 8 and 9) that meet this profile. ('409 Patent, col. 19:12-20, Table 4). An argument could be made that the claim term should be construed to require not just meeting the dissolution numbers, but doing so with a composition substantially similar to those disclosed as generating the inventive result.

VI. Other Allegations

  • Indirect Infringement: The complaint is primarily grounded in direct infringement under 35 U.S.C. § 271(e)(2) (the act of filing an ANDA for a patented drug) and § 271(a) (the post-launch making, using, and selling of the tablets). (Compl. ¶¶48, 63).
  • Willful Infringement: The complaint alleges willful infringement based on Lupin's continued infringing activities after the filing of the original complaint in this matter, which allegedly provided knowledge of the '409 patent. (Compl. ¶66). The extensive litigation history over the parent '780 patent may also be used to argue that Lupin acted despite an objectively high likelihood that its actions constituted infringement of a valid patent.

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

The complaint frames a focused dispute that appears to build directly on the parties' litigation over a parent patent. The central questions for the court will likely be:

  • A core issue will be one of evidentiary proof: Can Astellas demonstrate through discovery and expert testing that Lupin's commercially manufactured products, as a whole, consistently meet the precise two-point dissolution profile recited in Claim 1? Conversely, can Lupin show sufficient batch-to-batch variability or alternative testing results to create a genuine dispute of fact on infringement?
  • A key legal question, which will likely form the basis of the defense, will be one of patentability: Given the disclosure of the parent '780 patent and other prior art, does the specific dissolution profile claimed in the '409 patent constitute a non-obvious and patentably distinct invention, or is it an obvious variant of previously known modified-release formulations for mirabegron?