DCT

4:25-cv-00362

Eli Lilly & Co v. Humanwell Pharmaceutical US Inc

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: Eli Lilly & Co. v. Humanwell Pharmaceutical US, Inc., 4:25-cv-00362, E.D. Mo., 05/16/2025
  • Venue Allegations: Venue is alleged to be proper in the Eastern District of Missouri because Defendant Humanwell US is incorporated in Missouri, maintains its principal place of business within the district, and allegedly engaged in activities within the district relevant to the preparation and submission of the Abbreviated New Drug Application (ANDA) at issue.
  • Core Dispute: Plaintiffs allege that Defendants' filing of an ANDA to market a generic version of the migraine drug REYVOW® constitutes an act of infringement of a patent covering a specific crystalline hydrate form of the active ingredient, lasmiditan.
  • Technical Context: The dispute centers on specific crystalline structures (polymorphs) of an active pharmaceutical ingredient, which can significantly affect a drug's stability, bioavailability, and manufacturability, making them critical subject matter for patent protection in the pharmaceutical industry.
  • Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following Plaintiffs' receipt of a Paragraph IV certification notice from Defendant Humanwell US. In the notice, Humanwell US asserted that its proposed generic product would not infringe the patent-in-suit or that the patent is invalid. Such a certification is a statutory act of infringement that allows the patent holder to sue before the generic drug enters the market.

Case Timeline

Date Event
2016-12-06 U.S. Patent No. 11,053,214 Priority Date
2021-07-06 U.S. Patent No. 11,053,214 Issued
2025-01-31 REYVOW® New Chemical Entity Exclusivity Ends (alleged)
2025-02-10 Plaintiffs receive Defendants' Paragraph IV Certification Letter
2025-03-03 Defendants produce portions of ANDA and Drug Master File to Plaintiffs
2025-03-17 Defendants deliver samples of ANDA products to Plaintiffs
2025-05-16 Complaint Filed

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

U.S. Patent No. 11,053,214 - Compositions and methods related to pyridinoylpiperidine 5-HT1F agonists, issued July 6, 2021

The Invention Explained

  • Problem Addressed: The patent background describes a need for new migraine treatments that avoid the risk of coronary vasoconstriction associated with existing triptan drugs, which act on 5-HT1B/1D receptors (ʼ214 Patent, col. 1:35-42). It also identifies a separate, critical problem in pharmaceutical development: controlling the specific solid-state crystalline form (polymorph or pseudo-polymorph) of a drug, as different forms can have different physical properties affecting manufacturing, stability, and therapeutic utility (ʼ214 Patent, col. 2:13-19, 57-65).
  • The Patented Solution: The patent discloses the unexpected discovery of new pseudo-polymorphic forms of the 5-HT1F agonist lasmiditan hemisuccinate during commercial-scale manufacturing development (ʼ214 Patent, col. 3:15-19). The invention claims specific crystalline forms, including "Form D," a di-hydrate, which is defined by a unique and reproducible X-ray powder diffraction (XRPD) pattern. This provides a stable and characterizable solid form of the active pharmaceutical ingredient (ʼ214 Patent, Abstract; col. 3:24-32).
  • Technical Importance: Identifying, isolating, and patenting a specific, stable crystalline form of a drug substance is crucial for ensuring product consistency and quality, and is a key strategy for protecting pharmaceutical innovations from generic competition (ʼ214 Patent, col. 2:57-65).

Key Claims at a Glance

  • The complaint asserts infringement of the '214 patent, providing claim 1 as an "exemplary claim" (Compl. ¶37).
  • Independent Claim 1:
    • A crystalline Form D di-hydrate of the hemisuccinate salt of 2,4,6-trifluoro-N-[6-(1-methyl-piperidine-4-carbonyl)-pyridin-2-yl]-benzamide
    • characterized by an X-ray diffraction pattern when measured using Cu-Kα radiation
    • having at least peaks at about 18.7+/-0.2 degrees 2θ, 26.5+/-0.2 degrees 2θ, 27.0+/-0.2 degrees 2θ, 27.5+/-0.2 degrees 2θ and 27.8+/-0.2 degrees 2θ.
  • The complaint reserves the right to assert infringement of other claims of the ʼ214 patent (Compl. ¶38).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are the "Humanwell ANDA Products," specifically 50 mg and 100 mg generic lasmiditan hemisuccinate tablets for which Defendants seek FDA approval under ANDA No. 219669 (Compl. ¶¶ 10, 12).

Functionality and Market Context

The Humanwell ANDA Products are intended to be generic versions of Plaintiffs’ REYVOW® product, used for the acute treatment of migraine (Compl. ¶1). Defendants have represented that their ANDA contains data demonstrating the bioequivalence of their proposed products to REYVOW® (Compl. ¶30). The core of the infringement allegation is that the active pharmaceutical ingredient in these tablets will comprise the specific crystalline Form D claimed in the '214 patent (Compl. ¶38).

IV. Analysis of Infringement Allegations

The complaint alleges that the filing of ANDA No. 219669 is a statutory act of infringement under 35 U.S.C. § 271(e)(2) because the product that will be commercially manufactured and sold upon approval will meet all the limitations of at least claim 1 of the '214 patent (Compl. ¶¶ 38, 43). No probative visual evidence provided in complaint.

'214 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A crystalline Form D di-hydrate of the hemisuccinate salt of 2,4,6-trifluoro-N-[6-(1-methyl-piperidine-4-carbonyl)-pyridin-2-yl]-benzamide The complaint alleges, on information and belief, that the Humanwell ANDA Products comprise a crystalline Form D di-hydrate of the hemisuccinate salt of 2,4,6-trifluoro-N-[6-(1-methyl-piperidine-4-carbonyl)-pyridin-2-yl]-benzamide. This is based on information provided in the Humanwell ANDA and Drug Master File (DMF), which allegedly suggest the drug substance may convert to this form, and that the specified analytical methods are insufficient to prove its absence (¶¶ 38, 41-42). ¶38 col. 3:24-27
characterized by an X-ray diffraction pattern when measured using Cu-Kα radiation having at least peaks at about 18.7+/-0.2 degrees 2θ, 26.5+/-0.2 degrees 2θ, 27.0+/-0.2 degrees 2θ, 27.5+/-0.2 degrees 2θ and 27.8+/-0.2 degrees 2θ. The complaint alleges that the crystalline form in the Humanwell ANDA Products is characterized by an X-ray diffraction pattern with at least these same peaks. The allegation directly tracks the language of the claim (¶38). The complaint further suggests that the manufacturing process and specifications for the Humanwell ANDA Products permit the inclusion and/or conversion to crystalline Form D as claimed (¶41). ¶38 col. 3:28-32

Identified Points of Contention

  • Technical Question: A primary issue will be evidentiary: does the product described in Defendants' ANDA, and the product that would be made according to its specifications, in fact contain the claimed "crystalline Form D di-hydrate"? The complaint anticipates this dispute by alleging that information in the ANDA and DMF "suggest" that the substance "may convert" to Form D and that Defendants' analytical methods are not "sufficiently robust or sensitive" to detect it (Compl. ¶¶ 41, 42).
  • Scope Questions: The interpretation of the phrase "having at least peaks at about..." will likely be contentious. The dispute may focus on the scope of "about" when used in combination with an explicit numerical tolerance ("+/-0.2 degrees"), and on the evidence required to prove the presence of the five recited peaks in the accused product.

V. Key Claim Terms for Construction

The Term: "crystalline Form D di-hydrate"

  • Context and Importance: This term defines the patented subject matter. Proving its presence in the accused product is required for a finding of literal infringement. The case hinges on whether Defendants' lasmiditan hemisuccinate is this specific pseudo-polymorph.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent describes Form D more generally as a di-hydrate of Compound I (ʼ214 Patent, col. 8:30-36), which a party might argue allows for some variation as long as the fundamental di-hydrate character is present.
    • Evidence for a Narrower Interpretation: The patent provides a highly specific definition through instrumental analysis, including a characteristic XRPD pattern (Figure 1A; Table 2), a specific DSC thermogram (Figure 2), and a description as a "dihydrate of the hemi succinate salt" (ʼ214 Patent, col. 15:34-36). A party could argue the term is strictly limited to a substance meeting these precise physical and chemical parameters.

The Term: "about"

  • Context and Importance: This term modifies the numerical values of the XRPD peaks that define Form D. Its interpretation directly impacts the range of measured peak locations that can satisfy the claim limitation, making it central to the infringement analysis. Practitioners may focus on this term because its scope could be determinative if the accused product exhibits peaks that are close to, but not exactly at, the recited values.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification explicitly states that "the XRPD peak assignments can vary by plus or minus about 0.1, 0.2, 0.3, or 0.4 degrees" due to factors like instrument variation (ʼ214 Patent, col. 7:22-29). Plaintiffs may cite this language to argue for a flexible construction.
    • Evidence for a Narrower Interpretation: A party could argue that the explicit inclusion of a "+/-0.2 degrees" tolerance within the claim itself already accounts for expected variation, rendering the term "about" either redundant or limited to a very small additional range.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges facts to support contributory infringement, stating that the Humanwell ANDA Products are "especially made or adapted for use in infringing" the '214 patent and are "not a staple article of commerce or commodity of commerce suitable for substantial non-infringing use" (Compl. ¶47). Knowledge, a requirement for induced infringement, is alleged based on Defendants' filing of the ANDA with knowledge of the patent (Compl. ¶47).
  • Willful Infringement: The complaint does not use the word "willful" but alleges that this is an "exceptional case" warranting attorneys' fees under 35 U.S.C. § 285 (Compl. ¶49). The basis for this allegation is Defendants' act of filing the ANDA with a Paragraph IV certification, which establishes pre-suit knowledge of the patent and its alleged infringement.

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

  • A central question in this case will be evidentiary and technical: does the lasmiditan hemisuccinate manufactured according to the specifications in Defendants' ANDA actually contain the specific "crystalline Form D di-hydrate" as defined by the patent claims? The resolution will likely turn on sophisticated characterization of product samples and expert testimony regarding the potential for phase conversion during manufacturing.
  • A key legal issue will be one of claim construction: how should the court interpret the scope of the term "about" when it is used to modify XRPD peak locations that are already qualified by an explicit numerical tolerance ("+/-0.2 degrees")? The court's ruling on this term could be dispositive on the question of literal infringement.
  • The case also raises a classic Hatch-Waxman question: what is the proper basis for determining infringement under § 271(e)(2)? Will the analysis be limited to what is described in the ANDA, or will it focus on what the ANDA applicant is likely to sell if approved, especially in light of allegations that the final drug product may differ from the initially tested substance due to manufacturing processes?