DCT

1:25-cv-00828

Mitsubishi Tanabe Pharma Corp v. Lupin Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:25-cv-00828, D. Del., 07/03/2025
  • Venue Allegations: Venue is alleged to be proper for Lupin Pharmaceuticals, Inc. as it is a Delaware corporation. For Lupin Limited, venue is based on its alleged control over its Delaware-based subsidiary, purposeful availment of the district through business activities, and its intent to market the accused product in Delaware upon FDA approval.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's RADICAVA ORS® product constitutes an act of patent infringement under the Hatch-Waxman Act.
  • Technical Context: The technology concerns a stable, oral suspension formulation of the drug edaravone, used for the treatment of Amyotrophic Lateral Sclerosis (ALS), which provides a less burdensome administration route for patients compared to previous intravenous methods.
  • Key Procedural History: This lawsuit follows a "First Suit" filed by the Plaintiff against the Defendants concerning the same ANDA but different patents. The current action was triggered by a "Second Notice Letter" from Lupin, dated May 20, 2025, which provided certification against the patent-in-suit. Plaintiff's branded product, RADICAVA ORS®, has FDA-granted orphan drug exclusivity status set to expire on May 12, 2029.

Case Timeline

Date Event
2018-11-02 ’409 Patent Priority Date
2022-05-12 FDA approves NDA for RADICAVA ORS®
2024-03-28 FDA grants orphan drug exclusivity for RADICAVA ORS®
2024-11-19 Lupin sends First Notice Letter regarding other patents
2024-12-30 Plaintiff files "First Suit" against Lupin
2025-04-29 U.S. Patent No. 12,285,409 ('409 Patent) issues
2025-05-20 Lupin sends Second Notice Letter regarding '409 Patent
2025-05-21 Plaintiff receives Second Notice Letter
2025-07-03 Complaint Filing Date
2029-05-12 Orphan drug exclusivity for RADICAVA ORS® expires

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

U.S. Patent No. 12,285,409 - "Edaravone Suspension for Oral Administration", issued April 29, 2025

The Invention Explained

  • Problem Addressed: The patent describes Amyotrophic Lateral Sclerosis (ALS) as an "intractable disease" and notes that existing treatments, such as edaravone injections, impose a significant burden on patients and caregivers (’409 Patent, col. 6:43-48). The patent aims to solve the challenge of creating an oral drug product that is not only less burdensome but also achieves bioavailability comparable to an intravenous injection, a difficult task due to factors like absorption from the gastrointestinal tract and first-pass metabolism (’409 Patent, col. 28:40-49).
  • The Patented Solution: The invention is an oral suspension containing specific edaravone particles, a dispersant, and water (’409 Patent, Abstract). The formulation is engineered to maintain the edaravone in a solid particle state and is defined by several key parameters, including specific particle size distributions (D50 and D90), a specific concentration range of edaravone, and, critically, a specific pharmacokinetic (PK) profile (mean Cmax and AUC) in humans that demonstrates bioequivalence to the existing intravenous formulation (’409 Patent, col. 6:9-12; col. 30:15-32).
  • Technical Importance: The development of a stable oral suspension with predictable and effective bioavailability represented a significant improvement in the quality of life and administration options for ALS patients, for whom swallowing can become progressively difficult (Compl. ¶¶ 12-13).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the ’409 Patent without specifying them (Compl. ¶52). The first independent claim is Claim 1.
  • Independent Claim 1 requires:
    • An edaravone suspension for human oral administration, comprising water, edaravone particles, and a dispersant.
    • The dispersant must maintain the edaravone particles in a "solid particle state."
    • The edaravone particles must have a D50 particle size of 10-100 µm and a D90 particle size of 50-300 µm.
    • The blending amount of edaravone particles must be in the range of 0.2% to 36% (w/v).
    • When a 90-120 mg dose is orally administered to a human, it must result in a plasma mean Cmax of 500-2500 ng/mL and a mean AUC0-∞ of 1000-2500 h*ng/mL.
  • The complaint does not preclude the later assertion of dependent claims.

III. The Accused Instrumentality

Product Identification

  • Defendants' proposed generic edaravone oral suspension, as described in Abbreviated New Drug Application (ANDA) No. 219415 (Compl. ¶¶ 4, 41).

Functionality and Market Context

  • The accused product is an oral suspension formulated to contain 105 milligrams of edaravone per 5 mL dose (Compl. ¶42). It is intended to be a generic substitute for Plaintiff's RADICAVA ORS®, the reference listed drug in the ANDA filing (Compl. ¶43). The complaint alleges that Defendants seek FDA approval to commercially manufacture and sell this product in the United States prior to the expiration of the ’409 Patent (Compl. ¶¶ 44, 46).

IV. Analysis of Infringement Allegations

The complaint does not include a claim chart or detailed technical evidence of infringement, alleging that Defendants "imposed unreasonable conditions to obtain access" to the relevant information (Compl. ¶47). The infringement theory is based on the statutory act of filing an ANDA that seeks approval for a drug claimed in a patent. The following chart summarizes the allegations for Claim 1 based on the premise that the proposed generic is a bioequivalent copy of the patented product.

'409 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
An edaravone suspension for human oral administration, comprising: water; edaravone particles comprising edaravone and dispersed in the water; and a dispersant... Defendants' ANDA product is alleged to be an "edaravone oral suspension" intended as a generic version of RADICAVA ORS®, and therefore is alleged to contain edaravone particles, a dispersant, and water. ¶¶ 42, 44, 55 col. 6:9-12
...the edaravone particles in the suspension have a D50 particle size in a range of 10 µm to 100 µm and a D90 particle size of in a range of 50 µm to 300 µm... The complaint does not provide specific data but alleges that the proposed generic product meets all elements of one or more claims. To be a bioequivalent generic, the particle size distribution may fall within the claimed ranges. ¶¶ 52, 55 col. 30:20-24
...a blending amount of the edaravone particles is in a range of 0.2% (w/v) to 36% (w/v)... Defendants' product contains 105 mg of edaravone per 5 mL, which corresponds to a concentration of 2.1% (w/v). This falls within the claimed range. ¶42 col. 30:24-26
...when edaravone in the edaravone suspension is in a range of 90 to 120 mg, edaravone in a plasma exhibits a mean Cmax in a range of 500 to 2500 ng/ml and a mean AUC0-∞ in a range of 1000 to 2500 h*ng/mL when the edaravone suspension is orally administered to a human. The proposed generic product contains a 105 mg dose of edaravone. As a generic seeking to substitute for the patented product, it is alleged to be bioequivalent and therefore would exhibit the same pharmacokinetic profile upon administration. ¶¶ 42, 55 col. 30:26-32

No probative visual evidence provided in complaint.

  • Identified Points of Contention:
    • Technical Questions: A primary issue is evidentiary. What are the precise formulation details of Defendants' ANDA product? The complaint does not provide data on the specific dispersant used, the measured particle size distribution, or the actual PK profile of the proposed generic. The case may turn on whether discovery reveals that Defendants' product meets every numerical range and functional limitation required by the asserted claims.
    • Scope Questions: The interpretation of the pharmacokinetic (PK) limitation may be contested. For example, what are the precise conditions under which the "mean Cmax" and "mean AUC" must be measured to determine infringement? While the patent provides context from its own clinical trials, any deviation in testing protocols could raise questions of whether the accused product literally meets this limitation.

V. Key Claim Terms for Construction

  • The Term: "dispersant"

    • Context and Importance: This term defines a critical excipient in the formulation. Its construction is important because infringement may depend on whether the specific agent used in Defendants' product qualifies as a "dispersant" under the patent's definition. Practitioners may focus on this term because it is defined both functionally and by example in the patent.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent provides a broad functional definition, stating a dispersant is one that "allows the edaravone particles to be well dispersed in water without causing the edaravone particles to form secondary agglomerates" (’409 Patent, col. 7:7-10). It also provides performance-based tests, such as exhibiting a "transmission scattering light intensity of 1% or more" or a "contact angle of 80 degrees or less" under specified conditions (’409 Patent, col. 7:13-19, 41-44).
      • Evidence for a Narrower Interpretation: The specification provides a list of specific examples, including "polyvinyl alcohol, sucrose fatty acid ester, polysorbate, methylcellulose, and hypromellose" (’409 Patent, col. 7:40-42). A party could argue the term should be understood in light of these specific disclosed embodiments, rather than covering any compound that meets the functional tests.

  • The Term: "mean Cmax in a range of 500 to 2500 ng/ml" (and the corresponding AUC limitation)

    • Context and Importance: This is a product-by-process style limitation that defines the invention by its in-vivo performance rather than its physical composition alone. The infringement analysis for this element will require clinical or bioequivalence testing of the accused product, and the outcome will depend on how the test is conducted and how the term "mean" is construed.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent states that the "mean Cmax and the mean AUC0-∞ may each be an arithmetic mean value or a geometric mean value," which provides some flexibility in calculation (’409 Patent, col. 10:50-52).
      • Evidence for a Narrower Interpretation: The patent's detailed description of its own clinical study (Test Example 10) provides a specific context for how these values were obtained, including the dose (105 mg), subject population (42 Japanese healthy subjects), and conditions (fasting state) (’409 Patent, col. 26:5-18, Table 10). A party could argue that these parameters are integral to the claim's meaning and that infringement must be assessed under identical or highly similar conditions.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, Defendants will induce infringement by marketing the generic product with a label that instructs medical professionals and patients to administer it for the treatment of ALS, thereby directing them to perform the patented use (Compl. ¶¶ 56, 60).
  • Willful Infringement: Willfulness is alleged based on Defendants having "actual and constructive notice" of the ’409 Patent prior to and by virtue of their ANDA submission, which included a certification regarding the patent (Compl. ¶57). The complaint references Lupin’s "Second Notice Letter" as evidence of this knowledge (Compl. ¶4).

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

  • A central issue will be one of evidentiary proof: does the formulation detailed in Lupin's ANDA No. 219415, once revealed in discovery, fall within the specific numerical ranges for particle size (D50/D90) and pharmacokinetic performance (Cmax/AUC) recited in the asserted claims? The outcome of the case hinges on a direct technical comparison that is not yet possible from the complaint alone.
  • The case will also present a question of definitional scope: how will the court construe the term "dispersant"? Will the broad, functional definitions in the specification control, or will the term be interpreted more narrowly in light of the specific chemical classes provided as examples?
  • Finally, a key question is one of functional performance: assuming the accused product is tested, will it demonstrate the specific Cmax and AUC profile required by the claims when administered under conditions consistent with the patent's disclosure? This question highlights the challenge of enforcing claims defined by in-vivo results.