DCT
1:24-cv-00549
Mitsubishi Tanabe Pharma Corp v. Apotex Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Mitsubishi Tanabe Pharma Corporation (Japan)
- Defendant: Apotex Inc. (Canada) and Apotex Corp. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Oblon, McClelland, Maier & Neustadt LLP
- Case Identification: 1:24-cv-00549, D. Del., 05/03/2024
- Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware because Defendant Apotex Corp. is a Delaware corporation, and Defendant Apotex Inc. is a foreign corporation subject to personal jurisdiction in the district through its own actions and its control over its Delaware-based subsidiary.
- Core Dispute: Plaintiff alleges that Defendants’ filing of an Abbreviated New Drug Application (ANDA) for a generic version of Plaintiff’s RADICAVA ORS® constitutes an act of infringement of four patents related to oral suspensions of the drug edaravone.
- Technical Context: The technology concerns pharmaceutical formulations of edaravone, an approved treatment for amyotrophic lateral sclerosis (ALS), designed for oral administration to ease the burden of treatment compared to intravenous infusions.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 219256 and a corresponding notice letter to Plaintiff asserting that the patents-in-suit are invalid. The filing of the complaint within 45 days of receiving the notice letter triggers an automatic 30-month stay on FDA approval of the generic product.
Case Timeline
| Date | Event |
|---|---|
| 2018-11-02 | Priority Date for ’341, ’416, ’450, and ’352 Patents |
| 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 | FDA approves Plaintiff's RADICAVA ORS® (NDA No. 215446) |
| 2022-10-25 | U.S. Patent No. 11,478,450 Issues |
| 2023-11-28 | U.S. Patent No. 11,826,352 Issues |
| 2024-03-25 | Plaintiff receives Defendants' Notice Letter regarding ANDA No. 219256 |
| 2024-05-03 | Complaint filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,987,341 - “Edaravone Suspension for Oral Administration”
The Invention Explained
- Problem Addressed: The patent background describes amyotrophic lateral sclerosis (ALS) as an intractable neurodegenerative disease for which few treatments exist (’341 Patent, col. 1:41-45). While edaravone is a known therapeutic agent, its administration via injection is burdensome for patients and caregivers (Compl. ¶13). The technical challenge is to create a stable, effective oral formulation of edaravone.
- The Patented Solution: The invention is an aqueous oral suspension containing edaravone particles and a dispersant (’341 Patent, col. 1:63-66). The specific combination of ingredients is designed to keep the edaravone particles well-dispersed in the liquid, ensuring uniform dosing and achieving a therapeutic effect equivalent to that of an injection (’341 Patent, col. 4:65-68).
- Technical Importance: This technology provides an alternative to intravenous administration, potentially improving quality of life and treatment adherence for ALS patients (Compl. ¶13).
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims" without specifying particular claims (Compl. ¶55). Independent claim 1 is representative.
- Independent Claim 1: An edaravone suspension for human oral administration, comprising:
- water;
- edaravone particles comprising edaravone dispersed in the water; and
- a dispersant dispersing the edaravone particles in water such that the dispersant maintains the edaravone particles in a solid particle state in the water,
- wherein a blending amount of the edaravone particles is in a range of 0.5% (w/v) to 36% (w/v), and
- 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 does not explicitly reserve the right to assert dependent claims but makes broad allegations covering the patent.
U.S. Patent No. 11,241,416 - “Edaravone Suspension for Oral Administration”
The Invention Explained
- Problem Addressed: As a continuation of the application leading to the ’341 Patent, this patent addresses the same problem of creating a stable and effective oral suspension of edaravone for treating ALS (’416 Patent, col. 1:40-44).
- The Patented Solution: The solution is also an aqueous suspension of edaravone particles. This patent, however, defines the required dispersant functionally, by its ability to achieve a specific "transmission scattering light intensity" when tested according to a protocol described in the specification (’416 Patent, col. 4:9-25). This functional property is intended to ensure the edaravone particles remain properly suspended.
- Technical Importance: This patent claims the oral edaravone suspension using a functional performance characteristic of the dispersant, potentially capturing a broader range of formulations than those defined by a specific list of chemical ingredients.
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims" without specification (Compl. ¶66). Independent claim 1 is representative.
- Independent Claim 1: An edaravone suspension for human oral administration, comprising:
- water;
- edaravone particles comprising edaravone and dispersed in the water; and
- a dispersant exhibiting a transmission scattering light intensity of 1% or more and dispersing the edaravone particles in the water such that the dispersant maintains the edaravone particles in a solid particle state in the water,
- 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 complaint makes broad allegations covering the patent.
U.S. Patent No. 11,478,450 - “Edaravone Suspension for Oral Administration”
- Patent Identification: U.S. Patent No. 11,478,450, "Edaravone Suspension for Oral Administration," Issued October 25, 2022.
- Technology Synopsis: This patent, part of the same family, also covers an oral suspension of edaravone. Its claims focus on methods of treating ALS by administering the oral formulation according to specific dosing regimens, including daily or intermittent schedules, and achieving certain pharmacokinetic profiles (e.g., mean Cmax and AUC) (’450 Patent, Claim 1).
- Asserted Claims: The complaint broadly asserts infringement of "one or more claims" (Compl. ¶77). Independent claim 1 is representative.
- Accused Features: Defendants are accused of infringing by seeking FDA approval for their generic product with a label that will instruct physicians and patients to administer it for the treatment of ALS, thereby infringing the patented method (Compl. ¶¶ 78-79).
U.S. Patent No. 11,826,352 - “Edaravone Suspension for Oral Administration”
- Patent Identification: U.S. Patent No. 11,826,352, "Edaravone Suspension for Oral Administration," Issued November 28, 2023.
- Technology Synopsis: This patent is also in the same family and claims an edaravone suspension that includes a specific thickening agent, such as xanthan gum or tragacanth powder. The claims require the formulation to have a specific IDDSI (International Dysphagia Diet Standardisation Initiative) level, which relates to its viscosity and suitability for patients with difficulty swallowing (’352 Patent, Claim 1).
- Asserted Claims: The complaint broadly asserts infringement of "one or more claims" (Compl. ¶88). Independent claim 1 is representative.
- Accused Features: The accused product is the proposed generic edaravone oral suspension, which is alleged to contain the claimed combination of edaravone particles, a dispersant, and a thickening agent (Compl. ¶¶ 88-89).
III. The Accused Instrumentality
Product Identification
Defendants' proposed generic edaravone oral suspension, as described in Abbreviated New Drug Application (ANDA) No. 219256 (Compl. ¶2, ¶42).
Functionality and Market Context
The product is an oral suspension intended for the treatment of ALS (Compl. ¶2). The complaint alleges that the proposed product is a "generic copy" of MTPC's RADICAVA ORS® and identifies RADICAVA ORS® as the reference listed drug (Compl. ¶¶43-44). This regulatory status implies that Defendants' product is intended to have the same active ingredient, dosage form, strength, and route of administration as the branded product, and is expected to be bioequivalent.
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not provide specific claim charts or detailed infringement theories. The following summary is based on the allegation that the accused product is a "generic copy" of RADICAVA ORS® intended for the same therapeutic use.
’341 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 dispersed in the water... | The proposed product is an edaravone oral suspension. | ¶42 | col. 1:63-66 |
| and a dispersant... wherein a blending amount of the edaravone particles is in a range of 0.5% (w/v) to 36% (w/v)... | The complaint alleges the proposed generic copy meets all elements of one or more claims, implying its formulation contains a dispersant and edaravone particles within the claimed concentration range. | ¶58 | col. 26:15-18 |
| and 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's allegations imply that the dispersant used in the accused product is one of the chemical types listed in the claim. | ¶58 | col. 26:19-23 |
’416 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... and a dispersant... | The proposed product is an edaravone oral suspension containing a dispersant. | ¶42 | col. 2:1-3 |
| a dispersant exhibiting a transmission scattering light intensity of 1% or more... | The allegation of infringement implies the dispersant used in the accused product possesses the claimed functional property. | ¶69 | col. 4:9-25 |
| 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 complaint alleges infringement, implying the accused product's formulation meets the claimed concentration ranges for the dispersant and edaravone particles. | ¶69 | col. 28:59-62 |
Identified Points of Contention
- Scope Questions: A central question will be whether the specific combination of excipients (including the dispersant and thickening agent) and their concentrations in Defendants' proposed generic product fall within the scope of the claims of the asserted patents. Minor variations in formulation could be argued to place the product outside the literal scope of the claims.
- Technical Questions: For the ’416 Patent, a key factual dispute may arise regarding whether the dispersant in the accused product "exhibit[s] a transmission scattering light intensity of 1% or more" as measured by the specific test protocol detailed in the patent specification. For the ’352 Patent, a similar question exists regarding whether the accused product meets the claimed IDDSI level. The complaint provides no direct evidence on these technical, functional limitations.
V. Key Claim Terms for Construction
"dispersant" (’341 Patent, Claim 1)
- Context and Importance: The identity and function of the "dispersant" are central to the composition claims. While Claim 1 of the ’341 Patent provides a list of qualifying chemical classes, the scope of this term will be critical. The dispute will likely focus on whether the excipient used by Apotex functions as a "dispersant" in the claimed context and whether it falls within the specified chemical group.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification describes 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. 3:63-67). This functional definition could support arguing that chemically similar, but not identical, substances are equivalents.
- Evidence for a Narrower Interpretation: Claim 1 itself provides a closed list ("consisting of") of five specific types of chemical compounds. Defendants may argue that this language strictly limits the claim scope to only those dispersants explicitly recited, precluding infringement by any other type of dispersing agent.
"transmission scattering light intensity of 1% or more" (’416 Patent, Claim 1)
- Context and Importance: This term is a primary limitation distinguishing the ’416 Patent. Infringement depends entirely on whether the accused product meets this specific, measured performance characteristic. Practitioners may focus on this term because it is not a structural feature but a functional one, making infringement analysis dependent on laboratory testing according to the patent’s prescribed method.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party might argue that minor deviations from the test protocol that still demonstrate the required level of light scattering should be considered equivalent.
- Evidence for a Narrower Interpretation: The specification provides a detailed, multi-step protocol for measuring this value, including specific equipment (TURBISCAN Tower), sample preparation, bottle dimensions, and measurement height and time (’416 Patent, col. 4:15-25). A party would likely argue that claim construction must require strict adherence to this detailed protocol, as it is the only method provided to give meaning to the claimed value.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that upon approval, Defendants will induce infringement by instructing users, via the product's package insert and other materials, to administer the generic drug for the treatment of ALS in a manner that infringes the patented claims (Compl. ¶¶ 59, 63, 70, 74, 81, 85, 92, 96). This is a standard allegation in ANDA litigation where method claims are asserted.
- Willful Infringement: The complaint does not contain a specific count for willful infringement or use the word "willful." However, it alleges that Defendants had "actual and constructive notice" of each patent prior to filing their ANDA, which lays the factual predicate for a potential future claim of willfulness based on post-suit conduct (Compl. ¶¶ 60, 71, 82, 93).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of formulation scope: Will discovery reveal that the precise chemical composition of Apotex’s proposed generic product—specifically its choice of dispersant, thickening agent, and their respective concentrations—falls within the literal boundaries of the asserted composition claims?
- A key evidentiary question will be one of functional performance: Can Plaintiff demonstrate through testing that Apotex's formulation meets the quantitative functional limitations of the patents, such as the "transmission scattering light intensity" required by the ’416 Patent and the IDDSI level required by the ’352 Patent?
- A third central issue, not detailed in the complaint but foundational to the defense, will be claim validity: Can Apotex prove, by clear and convincing evidence, that the asserted claims are invalid as obvious over prior art related to other oral pharmaceutical suspensions, or that they lack adequate written description or enablement?