Eisai Co Ltd v. Alkem Laboratories Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiffs: Eisai Co., Ltd. (Japan), Eisai Inc. (Delaware), and Novartis Pharma AG (Switzerland)
  • Defendants: Alkem Laboratories Ltd. (India) and Ascend Laboratories, LLC (New Jersey)
  • Plaintiffs’ Counsel: Saul Ewing Arnstein & Lehr LLP; Paul Hastings LLP; Venable LLP
• Case Identification: Eisai Co., Ltd. v. Alkem Laboratories Ltd., 2:19-cv-14394, D.N.J., 06/27/2019
• Venue Allegations: Venue is alleged to be proper in the District of New Jersey based on Defendant Ascend Laboratories being a New Jersey corporation, its parent Alkem Laboratories conducting business in the state, and the act of sending a required notice letter regarding the Abbreviated New Drug Application (ANDA) to Plaintiff Eisai Inc.'s place of business in New Jersey.
• Core Dispute: Plaintiffs allege that Defendants' filing of an ANDA seeking FDA approval for a generic version of the antiepileptic drug Banzel® (rufinamide) is a statutory act of infringement of a patent claiming a specific, stable crystalline form of the drug's active ingredient.
• Technical Context: The dispute centers on polymorphism—the ability of a chemical compound to exist in multiple crystalline structures—a critical factor in pharmaceutical development that affects a drug's stability, manufacturability, and bioavailability.
• Key Procedural History: This is a Hatch-Waxman action initiated under 35 U.S.C. § 271(e)(2). The complaint was filed within the 45-day window following receipt of Defendants' Paragraph IV certification notice, which typically triggers an automatic 30-month stay on the FDA's approval of the generic application. A related case involving the same parties and patent was reportedly filed in the District of Delaware one day prior to this action.

Case Timeline

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

• Patent Identification: U.S. Patent No. 6,740,669, "Crystal Modification of 1-(2,6-Difluorobenzyl)-1H-1,2,3-Triazole-4-Carboxamide and its Use as Antiepileptic," issued May 25, 2004 (the “’669 Patent”).

The Invention Explained

• Problem Addressed: The patent's background explains that while the antiepileptic compound rufinamide was known, prior art provided "no information at all about possible crystal modifications obtained" (’669 Patent, col. 1:31-33). The existence of unknown or uncontrolled polymorphs of an active pharmaceutical ingredient (API) can lead to inconsistencies in drug product stability, solubility, and bioavailability, creating significant challenges for developing a reliable and effective medication (ʼ669 Patent, col. 5:49-56).
• The Patented Solution: The inventors discovered, isolated, and characterized distinct crystalline forms of rufinamide, including the novel forms designated A, A', B, and C (’669 Patent, col. 1:48-56). The invention claimed as "Crystal modification A" was found to possess "substantially better thermodynamic stability" than the other identified forms (’669 Patent, col. 5:39-42). This superior stability makes it particularly suitable for use in a solid pharmaceutical dosage form, as it ensures reproducible quality and bioavailability over time (’669 Patent, col. 5:49-56).
• Technical Importance: Controlling the polymorphic form of an API is a critical aspect of modern pharmaceutical science, essential for ensuring product consistency, shelf life, and predictable therapeutic performance, all of which are fundamental for regulatory approval and safe patient use.

Key Claims at a Glance

• The complaint asserts infringement of "one or more claims" of the ’669 Patent (Compl., Prayer for Relief ¶A). The foundational independent claims appear to be Claims 1 and 18.
• Independent Claim 1:
  • Crystal modification A of the compound 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide
  • characterized by characteristic lines at interplanar spacings (d values) of 10.5 Å, 5.14 Å, 4.84 Å, 4.55 Å, 4.34 Å, 4.07 Å, 3.51 Å, 3.48 Å, 3.25 Å, 3.19 Å, 3.15 Å, 3.07 Å, 2.81 Å,
  • determined by means of an X-ray powder pattern.
• Independent Claim 18:
  • A pharmaceutical composition
  • comprising a pharmaceutically acceptable carrier or diluent
  • and a therapeutically effective amount of crystal modification A of the compound 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide according to claim 1.
• The complaint's general allegation preserves the right to assert other claims, including dependent claims that further define Crystal modification A by other properties like FT-IR spectra or thermal analysis.

III. The Accused Instrumentality

Product Identification

• The "Alkem Generic Product," identified as an oral suspension containing 40 mg/mL of rufinamide, for which Defendants submitted Abbreviated New Drug Application (ANDA) No. 213410 to the U.S. Food and Drug Administration (FDA) (Compl. ¶22).

Functionality and Market Context

• The accused instrumentality is a proposed generic version of Plaintiffs' branded antiepileptic drug, Banzel® oral suspension (Compl. ¶24).
• Under the Hatch-Waxman Act, the filing of the ANDA itself is the statutory act of infringement, allowing for patent disputes to be litigated before the generic product enters the market (Compl. ¶27). The complaint alleges that by filing its ANDA, Alkem has represented to the FDA that its product contains the same active ingredient and has the same or substantially the same labeling as Banzel®, for which the '669 patent is listed in the FDA's "Orange Book" as covering the product or its use (Compl. ¶21, ¶24).

IV. Analysis of Infringement Allegations

The complaint does not contain a detailed claim chart. The infringement theory is statutory, based on the act of filing the ANDA under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶27). The core of the allegation is that the product described in ANDA No. 213410, if manufactured and sold, would infringe the ’669 Patent because the rufinamide API it contains is necessarily the claimed "Crystal modification A." The following table summarizes how the allegations for the accused oral suspension would likely map to the elements of a representative composition claim.

’669 Patent Infringement Allegations

No probative visual evidence provided in complaint.

• Identified Points of Contention:
  • Evidentiary Question: The primary question is one of fact: what is the actual polymorphic form of the rufinamide API specified in Alkem's confidential ANDA submission? The case will likely turn on characterization data within the ANDA (e.g., X-ray Powder Diffraction (XRPD), spectroscopy, thermal analysis) produced during discovery.
  • Technical Question: Does the rufinamide API in Alkem's product meet the specific characterization parameters required by the claims to be "Crystal modification A"? The dispute may center on whether Alkem’s API exhibits the XRPD peaks defined in claim 1, or if it is another polymorph (such as B or C, also described in the patent) or an amorphous form not covered by the asserted claims.

V. Key Claim Terms for Construction

• The Term: "Crystal modification A"
• Context and Importance: This term is the central limitation of the asserted claims and defines the patented invention. The outcome of the case hinges on whether the rufinamide in Alkem's proposed product falls within the scope of this term. Practitioners may focus on this term because the patent defines it by a set of physical properties, and any meaningful deviation in the accused product's API from these defined properties would be a primary basis for a non-infringement defense.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The independent claims define "Crystal modification A" by what the patent calls "characteristic lines" (Claim 1) or "characteristic" spectral bands (Claim 10). A party could argue that this language implies that only this recited set of features is required for infringement, and that other properties mentioned elsewhere in the specification or in dependent claims are merely exemplary, not required.
  • Evidence for a Narrower Interpretation: The patent provides highly specific data to distinguish Modification A from other polymorphs (A', B, and C), suggesting the definition is intended to be precise (’669 Patent, col. 1:48-56, Table 1). A party could argue that "Crystal modification A" must be strictly defined by the full set of detailed parameters disclosed in the specification (e.g., the extensive list of peaks in dependent Claim 2), and that any API that does not closely match this detailed fingerprint is a different, non-infringing form.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that the future commercial manufacture and sale of the Alkem Generic Product, for use "in accordance with its proposed labeling," would induce and/or contribute to the infringement of the '669 patent (Compl. ¶28). The basis for this allegation is the instruction set in the product's label, which would direct end-users to use the drug in an infringing manner.
• Willful Infringement: The complaint alleges that "Alkem was aware of the existence of the '669 patent" prior to filing its ANDA, as evidenced by its Paragraph IV certification, and knew that the filing constituted an act of infringement (Compl. ¶31). This allegation of pre-suit knowledge forms a potential basis for a claim of willful infringement.

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

The resolution of this case will likely depend on the answers to two central questions:

• A central question of polymorphic identity: Does the rufinamide API described in Alkem's confidential ANDA submission in fact possess the precise physical characteristics—specifically the X-ray powder diffraction pattern with the d-spacings defined in claim 1—of the patented "Crystal modification A," or does discovery reveal it to be a different, non-infringing polymorph or an amorphous solid?
• A key question of claim construction: How will the court define the boundaries of "Crystal modification A"? Will infringement require a strict, literal match to the "characteristic" properties recited in the claims, or will the definition accommodate some level of variation, and how will the patent's own detailed descriptions of other, distinct polymorphs (B and C) be used to delineate the scope of the claimed form?