DCT

1:23-cv-00759

Mitsubishi Tanabe Pharma Corp v. Cipla USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00759, D. Del., 08/30/2024
  • Venue Allegations: Venue is based on Defendants Cipla USA and Apotex Corp. being incorporated in Delaware, with further allegations that all defendants have purposefully availed themselves of the district through systematic business contacts and prior litigation activity.
  • Core Dispute: Plaintiff alleges that Defendants' submission of Abbreviated New Drug Applications (ANDAs) to the FDA, seeking to market generic versions of Plaintiff's RADICAVA ORS® product, constitutes an act of infringement of five patents related to oral suspensions of edaravone for the treatment of amyotrophic lateral sclerosis (ALS).
  • Technical Context: The technology concerns pharmaceutical formulations designed to deliver the drug edaravone orally as a suspension, providing a more convenient administration route for ALS patients compared to the previously available intravenous injection.
  • Key Procedural History: The action arises from ANDA filings by Cipla (No. 218428) and Apotex (No. 219256) under the Hatch-Waxman Act. The patents-in-suit are listed in the FDA’s Orange Book for RADICAVA ORS®. The FDA has granted Orphan Drug Exclusivity for RADICAVA ORS® through May 12, 2029. The complaint notes this is a consolidated action.

Case Timeline

Date Event
2018-11-02 Priority Date for all Patents-in-Suit
2021-04-27 U.S. Patent No. 10,987,341 Issues
2022-02-08 U.S. Patent No. 11,241,416 Issues
2022-05-12 Plaintiff’s RADICAVA ORS® (NDA No. 215446) Approved by FDA
2022-10-25 U.S. Patent No. 11,478,450 Issues
2023-05-31 Plaintiff Receives Cipla’s ANDA Notice Letter
2023-11-28 U.S. Patent No. 11,826,352 Issues
2024-03-25 Plaintiff Receives Apotex’s ANDA Notice Letter
2024-03-28 FDA Grants Orphan Drug Exclusivity for RADICAVA ORS®
2024-04-16 U.S. Patent No. 11,957,660 Issues
2024-08-30 Amended Complaint for Patent Infringement Filed

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

U.S. Patent No. 10,987,341 - "Edaravone Suspension for Oral Administration"

  • Issued: April 27, 2021

The Invention Explained

  • Problem Addressed: The patent describes amyotrophic lateral sclerosis (ALS) as an intractable motor neuron disease and notes the significant burden placed on patients and caregivers by existing treatments, which included intravenous (IV) administration of edaravone (’341) Patent, col. 4:41-44, 65-66).
  • The Patented Solution: The invention is an oral suspension of edaravone particles in water using a specific dispersant. This formulation is designed to achieve a therapeutic effect and bioavailability equivalent to an IV injection, thereby reducing the burden of administration for ALS patients (’341 Patent, Abstract; col. 4:62-66). The patent's FIGURE graphically depicts the comparable pharmacokinetic profiles of the oral suspension (PO) and the IV injection (IV), illustrating this equivalence.
  • Technical Importance: The development of a stable oral suspension with bioavailability comparable to an IV injection represented a significant improvement in the quality of life and convenience for ALS patients requiring edaravone therapy (Compl. ¶10-11).

Key Claims at a Glance

The complaint does not identify specific asserted claims. Claim 1 is the broadest independent composition claim.

  • Independent Claim 1:
    • An edaravone suspension for human oral administration, comprising:
    • water;
    • edaravone particles comprising edaravone dispersed in the water;
    • a dispersant that maintains the edaravone particles in a solid state in the water;
    • wherein the amount of edaravone particles is between 0.5% (w/v) and 36% (w/v); and
    • the dispersant is selected from polyvinyl alcohol, methylcellulose, hypromellose, sucrose fatty acid ester, and polysorbate.

U.S. Patent No. 11,241,416 - "Edaravone Suspension for Oral Administration"

  • Issued: February 8, 2022

The Invention Explained

  • Problem Addressed: As with the parent ’341 Patent, this invention addresses the need for a less burdensome, orally administered edaravone formulation for ALS patients (’416) Patent, col. 4:42-45).
  • The Patented Solution: The ’416 Patent claims an oral edaravone suspension but adds functional limitations to the dispersant. The invention requires the dispersant to exhibit a "transmission scattering light intensity of 1% or more," a physical property measured to ensure proper dispersion of the edaravone particles and stability of the suspension (’416 Patent, col. 5:5-26).
  • Technical Importance: This patent focuses on specific physical characteristics of the formulation's components to ensure the suspension is stable and effective, refining the solution for creating a viable oral alternative to IV edaravone (Compl. ¶10-11).

Key Claims at a Glance

The complaint does not identify specific asserted claims. Claim 1 is a representative independent claim.

  • Independent Claim 1:
    • An edaravone suspension for human oral administration, comprising:
    • water;
    • edaravone particles dispersed in the water;
    • a dispersant exhibiting a transmission scattering light intensity of 1% or more;
    • wherein the dispersant maintains the edaravone particles in a solid state; and
    • wherein the blending amount of the dispersant is between 0.001% (w/v) and 1.0% (w/v), and the edaravone particles is between 0.5% (w/v) and 36% (w/v).

U.S. Patent No. 11,478,450 - "Edaravone Suspension for Oral Administration"

  • Issued: October 25, 2022
  • Technology Synopsis: This patent claims a method of treating ALS by administering an oral edaravone formulation to a patient in need thereof. It addresses the same technical challenge of providing an effective oral therapy for ALS by claiming the specific act of using the formulation for treatment (’450) Patent, Abstract; col. 26:27-56).
  • Asserted Claims: The complaint does not specify which claims are asserted (Compl. ¶141-152).
  • Accused Features: The accused feature is the act of administering the proposed generic products according to their FDA-approved labeling, which will be for the treatment of ALS (Compl. ¶142, ¶154).

U.S. Patent No. 11,826,352 - "Edaravone Suspension for Oral Administration"

  • Issued: November 28, 2023
  • Technology Synopsis: This patent claims a composition for an edaravone suspension that includes a specific thickening agent (xanthan gum or tragacanth powder) to achieve a viscosity corresponding to an International Dysphagia Diet Standardisation Initiative (IDDSI) level of 1 to 3. This solves the additional problem of ensuring the suspension is safe and easy to swallow for ALS patients who may suffer from dysphagia (’352) Patent, col. 29:1-24).
  • Asserted Claims: The complaint does not specify which claims are asserted (Compl. ¶165-176).
  • Accused Features: Defendants' proposed generic products are alleged to be bioequivalent oral suspensions that contain a thickening agent and have viscosity properties falling within the scope of the claims (Compl. ¶166, ¶178).

U.S. Patent No. 11,957,660 - "Edaravone Suspension for Oral Administration"

  • Issued: April 16, 2024
  • Technology Synopsis: This patent claims an edaravone suspension that contains a thickening agent but is formulated without a preservative. The claims require that the formulation does not support bacterial growth for at least 28 days, addressing the technical challenge of creating a microbiologically stable, multi-dose liquid formulation without common preservatives (’660) Patent, Abstract; col. 26:35-50).
  • Asserted Claims: The complaint does not specify which claims are asserted (Compl. ¶189-200).
  • Accused Features: Defendants' proposed generic products are alleged to be formulations that are stable and effective without the use of a preservative, thereby infringing the claims (Compl. ¶190, ¶202).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are the proposed generic drug products for which Cipla and Apotex have filed ANDA No. 218428 and ANDA No. 219256, respectively (Compl. ¶70, ¶79).
  • Functionality and Market Context:
    • Both proposed products are identified as "edaravone oral suspension containing 105 milligrams of edaravone (the active pharmaceutical ingredient) per 5 mL" (Compl. ¶71, ¶80). This formulation is intended for the treatment of ALS and identifies Plaintiff's RADICAVA ORS® as the reference listed drug, meaning the generic products must be bioequivalent to it (Compl. ¶72, ¶81).
    • The complaint characterizes RADICAVA ORS® as "highly successful" and one of only a few approved treatments for ALS, positioning the accused generic products to compete directly in this critical therapeutic market upon FDA approval (Compl. ¶2, ¶6).
    • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint alleges infringement of all five patents-in-suit based on the Defendants' ANDA filings. Because the full details of the generic formulations are not yet public, the allegations are made on information and belief that a product bioequivalent to RADICAVA ORS® must necessarily meet the patent claim limitations.

  • ’341 Patent Infringement Allegations
Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
An edaravone suspension for human oral administration... The accused products are oral suspensions of edaravone intended for human administration to treat ALS. ¶71, ¶80 col. 25:56-57
...comprising: water; edaravone particles comprising edaravone dispersed in the water; and a dispersant... The accused products are alleged to be aqueous suspensions containing undissolved edaravone particles and a dispersant necessary to achieve stability and bioequivalence. ¶94, ¶106 col. 26:1-5
...the dispersant is at least one dispersant selected from the group consisting of polyvinyl alcohol, methylcellulose, hypromellose, sucrose fatty acid ester and polysorbate. The complaint alleges on information and belief that the accused products contain a dispersant from the claimed chemical class to replicate the formulation of the reference drug. ¶94, ¶106 col. 26:16-24
...a blending amount of the edaravone particles is in a range of 0.5% (w/v) to 36% (w/v)... The accused products contain 105 mg of edaravone per 5 mL, which corresponds to a concentration of 2.1% (w/v), falling within the claimed range. ¶71, ¶80 col. 26:13-15
  • ’416 Patent Infringement Allegations
Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
An edaravone suspension for human oral administration... The accused products are oral suspensions of edaravone intended for human administration to treat ALS. ¶71, ¶80 col. 27:35-37
...a dispersant exhibiting a transmission scattering light intensity of 1% or more... The complaint does not provide specific data on this physical property but alleges on information and belief that the generic products must use a dispersant meeting this functional limitation to achieve bioequivalence. ¶118, ¶130 col. 27:42-43
...wherein a blending amount of the dispersant is in a range of 0.001% (w/v) to 1.0% (w/v), a blending amount of the edaravone particles is in a range of 0.5% (w/v) to 36% (w/v). The accused products' edaravone concentration of 2.1% (w/v) meets the particle amount limitation. The complaint alleges on information and belief that the dispersant concentration also falls within the claimed range. ¶71, ¶80, ¶118, ¶130 col. 28:1-3
  • Identified Points of Contention:
    • Scope Questions: A central dispute may arise over the specific excipients used in the generic formulations. The case raises the question of whether Defendants' chosen "dispersant" is the same as, or equivalent to, one of the specific chemical classes required by Claim 1 of the ’341 Patent. Further, for the ’416 Patent, a key question will be whether the Defendants' dispersant actually performs the function of exhibiting a "transmission scattering light intensity of 1% or more."
    • Technical Questions: The primary technical question is one of bioequivalence versus infringement. What evidence does the complaint provide that achieving bioequivalence with RADICAVA ORS® requires practicing the specific combination of elements in each asserted claim? Defendants may argue they developed a formulation with different excipients, concentrations, or physical properties that achieves the same clinical result without infringing the patents.

V. Key Claim Terms for Construction

  • The Term: "dispersant"

    • Context and Importance: This term is foundational to the composition claims of the asserted patents. The identity and function of the "dispersant" are critical limitations. Practitioners may focus on this term because the Defendants could argue that their chosen excipient, while performing a stabilizing function, is not a "dispersant" as contemplated by the patent, or that it falls outside the specific classes recited in claims like Claim 1 of the ’341 Patent.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification defines a dispersant functionally as any substance that "allows the edaravone particles to be well dispersed in water without causing the edaravone particles to form secondary agglomerates" (’341 Patent, col. 5:62-66). This functional language could support a broader scope beyond the specific examples provided.
      • Evidence for a Narrower Interpretation: The specification provides specific examples of dispersants (e.g., "polyvinyl alcohol, sucrose fatty acid ester, polysorbate, methylcellulose and hypromellose") and describes specific tests for identifying them, such as contact angle and transmission scattering light intensity tests (’341 Patent, col. 5:55-61; col. 17:10-21). This could support a narrower construction limited to the recited classes or those that meet the patent's specific test criteria.

  • The Term: "maintains the edaravone particles in a solid particle state"

    • Context and Importance: This term distinguishes the claimed invention as a suspension from a solution. Its construction is important because if a significant portion of the active ingredient in the accused products dissolves rather than remains as solid particles, Defendants could argue non-infringement.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: This phrase could be interpreted to mean simply that the formulation is not a complete solution and contains some amount of undissolved, solid edaravone particles.
      • Evidence for a Narrower Interpretation: The patent emphasizes the importance of redispersibility after settling, showing test results where particles are redispersed within seconds after prolonged storage simulation (’341 Patent, Test Example 6, col. 20:35-44). This might support an argument that the term implies a certain degree of physical stability and minimal dissolution over time, not just the mere presence of solid particles.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon approval, Defendants will induce infringement by marketing their generic products with labels that instruct physicians and patients to administer the drug for the treatment of ALS (Compl. ¶102, ¶115). This directly implicates the asserted method-of-use claims, such as those in the ’450 Patent.
  • Willful Infringement: The complaint does not explicitly plead "willful infringement." However, it alleges that Defendants had "actual and constructive notice" of the patents prior to filing their ANDAs and proceeded "without adequate justification for asserting that the... patent[s] [are] invalid and/or not infringed" (Compl. ¶99-100, ¶112-113). These allegations could form the basis for a later claim of willful infringement or a request for enhanced damages.

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

  • A core issue will be one of formulation identity and equivalence: do the specific excipients, concentrations, and resulting physical properties of the Defendants’ proposed generic products fall within the scope of the patent claims? The case will likely depend on discovery into the precise nature of the accused formulations and whether they practice the claimed inventions or represent a successful "design-around" that achieves bioequivalence through a different technical approach.
  • A second central question will be one of patent validity: are the claimed formulations non-obvious improvements over the prior art? The dispute may focus on whether creating a stable, injection-equivalent oral suspension of edaravone using the claimed dispersants and thickening agents would have been obvious to a person of ordinary skill in pharmaceutical formulation at the time of the invention.