DCT
1:24-cv-01423
Mitsubishi Tanabe Pharma Corp v. Lupin Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Mitsubishi Tanabe Pharma Corporation (Japan)
- Defendant: Lupin Limited (India) and Lupin Pharmaceuticals, Inc. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:24-cv-01423, D. Del., 12/30/2024
- Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware because Defendant Lupin Pharmaceuticals, Inc. is a Delaware corporation and Defendant Lupin Limited, a foreign corporation, conducts substantial business in and has systematic contacts with Delaware, including through the activities of its U.S. subsidiary.
- Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's RADICAVA ORS® product constitutes an act of infringement of five patents related to oral suspension formulations of the active ingredient edaravone.
- Technical Context: The technology pertains to pharmaceutical formulations that allow edaravone, a treatment for amyotrophic lateral sclerosis (ALS), to be administered as a stable oral suspension, providing a less burdensome alternative to intravenous delivery.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' notification to Plaintiff of their ANDA filing. The complaint states it was filed within the 45-day statutory window, which triggers an automatic 30-month stay on the FDA’s approval of Defendants' generic product.
Case Timeline
| Date | Event |
|---|---|
| 2018-11-02 | Patent Priority Date ('341, '416, '450, '352, '660 Patents) |
| 2021-04-27 | '341 Patent Issue Date |
| 2022-02-08 | '416 Patent Issue Date |
| 2022-05-12 | FDA approval of RADICAVA ORS® New Drug Application |
| 2022-09-01 | Lupin Pharmaceuticals submits FOIA request for Radicava ORS® data |
| 2022-10-25 | '450 Patent Issue Date |
| 2023-11-28 | '352 Patent Issue Date |
| 2024-03-28 | FDA grants orphan drug exclusivity for RADICAVA ORS® |
| 2024-04-16 | '660 Patent Issue Date |
| 2024-11-20 | Plaintiff receives Defendants' ANDA Notice Letter |
| 2024-12-30 | Complaint Filing Date |
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 describes edaravone as an effective therapeutic agent for ALS but notes that its commercial form was an injection, which is burdensome for patients and their caregivers (U.S. Patent No. 10,987,341, col. 1:65-67). The patent further notes the technical difficulty of creating an oral drug product that is biologically equivalent to an intravenous injection, due to factors like absorption from the gastrointestinal tract and first-pass metabolism ('341 Patent, col. 24:12-22).
- The Patented Solution: The invention is an oral suspension that combines edaravone particles with water and a specific "dispersant" ('341 Patent, Abstract). This dispersant is chosen to ensure the edaravone particles are uniformly dispersed in the liquid and can be quickly redispersed after settling, thereby achieving a therapeutic effect equivalent to that of an injection ('341 Patent, col. 1:63-67). The claims require the dispersant to maintain the edaravone in a "solid particle state" ('341 Patent, col. 26:12-14).
- Technical Importance: This technology provided a means to deliver edaravone orally, which can reduce the burden on ALS patients and improve their quality of life compared to treatment requiring intravenous infusions ('341 Patent, col. 1:65-67).
Key Claims at a Glance
- The complaint asserts at least Independent Claim 1 (Compl. ¶58).
- Essential elements of Claim 1:
- An edaravone suspension for human oral administration comprising water, edaravone particles, and a dispersant.
- The dispersant must disperse the edaravone particles and maintain them "in a solid particle state in the water."
- The blending amount of edaravone particles must be in a range of 0.5% (w/v) to 36% (w/v).
- The dispersant must be selected from the group of polyvinyl alcohol, methylcellulose, hypromellose, sucrose fatty acid ester, and polysorbate.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 11,241,416 - "Edaravone Suspension for Oral Administration"
The Invention Explained
- Problem Addressed: The patent addresses the same technical challenge as the ’341 Patent: developing a stable, bioavailable oral formulation of edaravone to provide a less burdensome alternative to intravenous administration for ALS patients ('416 Patent, col. 2:1-5).
- The Patented Solution: The invention is an oral suspension of edaravone particles in water, using a dispersant defined by specific, measurable physical properties. Instead of listing specific chemical identities for the dispersant, the claims define it functionally, requiring that it exhibit a "transmission scattering light intensity of 1% or more" under specified test conditions ('416 Patent, col. 27:55-65, Claim 1). This functional definition ensures the selected agent can effectively disperse the edaravone particles to achieve the desired therapeutic effect ('416 Patent, col. 4:1-10).
- Technical Importance: This approach provides an alternative way to define and claim suitable dispersants based on performance characteristics rather than chemical structure, potentially broadening the scope of protective coverage for the oral suspension technology.
Key Claims at a Glance
- The complaint asserts at least Independent Claim 1 (Compl. ¶70).
- Essential elements of Claim 1:
- An edaravone suspension for human oral administration comprising water, edaravone particles, and a dispersant.
- The dispersant must exhibit a "transmission scattering light intensity of 1% or more" and maintain the edaravone particles "in a solid particle state."
- The blending amount of the dispersant must be in a range of 0.001% (w/v) to 1.0% (w/v).
- The blending amount of edaravone particles must be in a range of 0.5% (w/v) to 36% (w/v).
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 11,478,450 - "Edaravone Suspension for Oral Administration"
- Technology Synopsis: This patent is directed to a method of treating ALS by orally administering a formulation of edaravone. The claims specify daily dosage amounts (e.g., 60 to 400 mg/day) and administration schedules, including intermittent schedules, intended to achieve therapeutic plasma concentrations comparable to those from intravenous delivery ('450 Patent, Abstract; col. 25:67-26:24).
- Asserted Claims: At least Independent Claim 1 (Compl. ¶82).
- Accused Features: Defendants' proposed generic product and its associated labeling are alleged to infringe because they will instruct physicians and patients to administer the drug according to the claimed methods of treatment (Compl. ¶82, ¶86).
U.S. Patent No. 11,826,352 - "Edaravone Suspension for Oral Administration"
- Technology Synopsis: This patent claims an edaravone oral suspension that includes a specific type of thickening agent, such as xanthan gum or tragacanth powder. The addition of the thickening agent is intended to produce a specific viscosity (defined by an IDDSI level of 1 to 3), which can aid patients with dysphagia (difficulty swallowing) without compromising the suspension's stability or bioavailability ('352 Patent, Abstract; col. 5:25-41).
- Asserted Claims: At least Independent Claim 1 (Compl. ¶94).
- Accused Features: Defendants' proposed generic suspension is alleged to contain the claimed combination of edaravone particles, a dispersant, and a thickening agent meeting the claim limitations (Compl. ¶94, ¶97).
U.S. Patent No. 11,957,660 - "Edaravone Suspension for Oral Administration"
- Technology Synopsis: This patent claims an edaravone oral suspension that is formulated without a conventional preservative (e.g., parabens, sodium benzoate). The invention is based on the discovery that a specific combination of edaravone, a dispersant, and a thickening agent can resist bacterial growth and pass standard preservation efficacy tests without the need for a separate preservative ingredient ('660 Patent, Abstract; col. 7:16-24).
- Asserted Claims: At least Independent Claim 1 (Compl. ¶106).
- Accused Features: Defendants' proposed generic suspension is alleged to be a preservative-free formulation that meets all the elements of the claims (Compl. ¶106, ¶109).
III. The Accused Instrumentality
Product Identification
- Defendants' proposed generic edaravone oral suspension, which is the subject of Abbreviated New Drug Application (ANDA) No. 219415 (Compl. ¶2, ¶45).
Functionality and Market Context
- The accused product is an oral suspension formulated to contain 105 milligrams of edaravone per 5 mL dose (Compl. ¶46). It is intended to be a generic equivalent of Plaintiff’s RADICAVA ORS® product for the treatment of ALS (Compl. ¶47-48). As a generic, the product seeks to compete with the branded drug, which the complaint describes as "highly successful" and as providing a "clinically superior option for patients" compared to intravenous administration (Compl. ¶2, ¶10). The complaint alleges that Plaintiff has not had access to the ANDA or samples of the accused product, and thus its allegations are based on information and belief derived from Defendants' legal notice (Compl. ¶52-53).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The infringement allegations are made under 35 U.S.C. § 271(e)(2), which defines the submission of an ANDA seeking approval to market a generic version of a patented drug as a technical act of infringement. The complaint alleges on "information and belief" that the product described in ANDA No. 219415 will meet the limitations of the asserted claims (Compl. ¶58, ¶70).
10,987,341 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 accused product is an edaravone oral suspension. | ¶46, ¶48 | col. 26:1-5 |
| a dispersant dispersing the edaravone particles in water such that the dispersant maintains the edaravone particles in a solid particle state in the water, | The accused product contains a dispersant from the claimed group that maintains edaravone as solid particles. | ¶58, ¶61 | col. 26:6-14 |
| wherein a blending amount of the edaravone particles is in a range of 0.5% (w/v) to 36% (w/v)... | The accused product contains 105 mg of edaravone per 5 mL, which corresponds to a concentration of 2.1% (w/v), falling within the claimed range. | ¶46 | col. 26:15-16 |
| 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 accused product is alleged to contain at least one of the specified dispersants. | ¶58, ¶61 | col. 26:16-20 |
- Identified Points of Contention:
- Scope Questions: A primary question will be factual: does an excipient in Defendants' formulation fall within the claimed Markush group of "dispersant" chemicals? The complaint's allegation is based on information and belief, and the actual composition of the generic product will be a central point of discovery.
- Technical Questions: What evidence does the complaint provide that an excipient in the accused product performs the claimed function of "maintain[ing] the edaravone particles in a solid particle state"? This functional language raises the question of whether an excipient that performs other primary functions (e.g., as a binder or filler) but has an incidental dispersing effect would be covered by the claim.
11,241,416 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... | The accused product is an edaravone oral suspension. | ¶46, ¶48 | col. 27:55-58 |
| a dispersant exhibiting a transmission scattering light intensity of 1% or more and dispersing the edaravone particles... | The accused product is alleged to contain a dispersant that meets this specific, testable physical property. | ¶70, ¶73 | col. 27:59-60 |
| wherein a blending amount of the dispersant is in a range of 0.001% (w/v) to 1.0% (w/v)... | The accused product is alleged to contain a dispersant within this concentration range. | ¶70, ¶73 | col. 28:1-3 |
| a blending amount of the edaravone particles is in a range of 0.5% (w/v) to 36% (w/v). | The accused product's concentration of 2.1% (w/v) falls within the claimed range. | ¶46 | col. 28:4-5 |
- Identified Points of Contention:
- Scope Questions: This claim defines the dispersant functionally. The central question will be whether the specific excipients used in Defendants' product, at their specified concentrations, actually "exhibit[] a transmission scattering light intensity of 1% or more" under the test conditions described in the patent.
- Technical Questions: What evidence does the complaint provide to support the allegation that Defendants' formulation meets this specific functional limitation? Resolution of this issue will likely require laboratory testing of Defendants' product once it is produced in discovery.
V. Key Claim Terms for Construction
The Term: "dispersant"
Context and Importance: This term is foundational to the asserted claims of the ’341 and ’416 patents. The infringement analysis will turn on whether an excipient in Defendants' product is properly categorized as a "dispersant" performing the claimed functions. Practitioners may focus on this term because its construction will determine whether the claims cover a narrow set of specific agents or a broader class of common pharmaceutical excipients that may possess dispersing properties.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides several examples of suitable dispersants, including common pharmaceutical excipients like polyvinyl alcohol and methylcellulose ('341 Patent, col. 5:27-31). The patent also provides a broad functional description, stating that the dispersant "allows the edaravone particles to be well dispersed in water" ('341 Patent, col. 5:63-65).
- Evidence for a Narrower Interpretation: The specification also defines dispersants by their performance in specific tests, such as exhibiting a "transmission scattering light intensity of 1% or more" or a "contact angle of 80 degrees or less" ('341 Patent, col. 5:1-40). A defendant could argue that to qualify as a "dispersant" under the patent, an excipient must satisfy these specific quantitative metrics, not merely have a general dispersing effect.
The Term: "maintains the edaravone particles in a solid particle state"
Context and Importance: This phrase, present in the independent claims of both the ’341 and ’416 patents, defines a key function of the claimed "dispersant." The dispute may center on the degree to which this language permits any dissolution of the active ingredient.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party could argue that in the context of a "suspension," this term means that the formulation's primary mechanism of delivery involves solid particles, even if some minor or incidental dissolution occurs in the aqueous medium.
- Evidence for a Narrower Interpretation: A party could argue this phrase requires an active function of preserving the solid state, distinguishing the claimed invention from formulations using standard wetting agents or excipients that might not prevent dissolution. The patent consistently refers to the invention as a "suspension" to achieve bioavailability equivalent to an injection, suggesting the solid state is critical ('341 Patent, col. 1:63-67).
VI. Other Allegations
- Indirect Infringement: The complaint includes requests for a declaration that future commercialization of the accused product will constitute induced and contributory infringement (Compl. ¶66, ¶78, ¶90, ¶102, ¶114). The alleged basis for such infringement is that Defendants' product labeling and instructions would direct medical professionals and patients to use the generic drug in a manner that directly infringes the asserted claims.
- Willful Infringement: The complaint does not use the term "willful infringement." However, it alleges that Defendants had "actual and constructive notice" of each of the patents-in-suit prior to filing their ANDA (Compl. ¶63, ¶75, ¶87, ¶99, ¶111). These allegations could form the basis for a later claim of willfulness.
VII. Analyst’s Conclusion: Key Questions for the Case
The resolution of this case will likely depend on the answers to several central questions that bridge factual evidence and legal interpretation.
- A core issue will be one of factual composition: What are the precise ingredients and their concentrations in Defendants' proposed generic formulation? The case cannot proceed to a substantive infringement analysis until discovery reveals whether the accused product contains the specific dispersants, thickening agents, and concentration ranges required by the various asserted claims.
- A key legal question will be one of definitional scope: How will the court construe the term "dispersant" and its required function of "maintain[ing] the edaravone particles in a solid particle state"? Whether this term is interpreted broadly to cover common excipients with incidental dispersing effects or narrowly to require satisfaction of the specific functional tests in the specification will be critical to the infringement outcome.
- A central evidentiary question will be one of functional performance: Assuming the composition of Defendants' product is revealed, does it meet the quantitative, functional limitations of the claims, such as the "transmission scattering light intensity" requirement of the ’416 patent or the viscosity level required by the ’352 patent? This will likely require expert testimony and comparative laboratory testing.