DCT

1:24-cv-06765

Eisai R&D Management Co Ltd v. DR Reddy's Laboratories Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-06765, D.N.J., 06/06/2024
  • Venue Allegations: Venue is alleged to be proper as to the foreign defendant, DRL Ltd., under 28 U.S.C. § 1391(c)(3), and as to the domestic defendant, DRL Inc., because it is incorporated and resides in New Jersey, under 28 U.S.C. § 1400(b).
  • Core Dispute: Plaintiffs allege that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to the FDA seeking approval to market generic lenvatinib mesylate capsules constitutes an act of infringement of three patents related to specific crystalline salt forms and high-purity compositions of the drug.
  • Technical Context: The dispute concerns the active pharmaceutical ingredient in LENVIMA®, a tyrosine kinase inhibitor used in oncology, highlighting the importance of crystalline structure and purity in pharmaceutical patenting.
  • Key Procedural History: The litigation was triggered by a Paragraph IV Notice Letter, dated April 22, 2024, in which Defendants notified Plaintiffs of their ANDA filing and certified that their generic products would not infringe the asserted patents or that the patents are invalid. This complaint was filed within the 45-day statutory period provided by the Hatch-Waxman Act, triggering a potential 30-month stay of FDA approval for the generic product.

Case Timeline

Date Event
2003-12-25 ’208 Patent Priority Date
2009-11-03 ’208 Patent Issue Date
2014-08-28 ’393 and ’547 Patents Priority Date
2015-02-13 Plaintiffs' LENVIMA® (NDA No. 206947) Approved by FDA
2019-09-10 ’393 Patent Issue Date
2021-11-30 ’547 Patent Issue Date
2024-04-22 Defendants Send Paragraph IV Notice Letter
2024-06-06 Complaint Filing Date

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

U.S. Patent No. 7,612,208 - "Crystalline Form of the Salt of 4-(3-Chloro-4-(Cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide or the Solvate of the Salt and a Process for Preparing the Same"

  • Issued: November 3, 2009

The Invention Explained

  • Problem Addressed: The patent's background describes a "long-felt need" for a form of the subject quinoline carboxamide compound that has "high usability as a medicament and superior characteristics in terms of physical properties and pharmacokinetics" compared to its free-form version (Compl. ¶33; ’208 Patent, col. 1:28-36).
  • The Patented Solution: The invention provides specific crystalline salt forms of the active pharmaceutical ingredient, including hydrochloride, hydrobromide, methanesulfonate (mesylate), and ethanesulfonate salts. These crystalline salt forms are disclosed as having improved properties, such as dissolution rate and bioavailability, which are critical for an effective oral medication (’208 Patent, Abstract; col. 7:51-54). Figure 1 of the patent illustrates the significantly higher blood concentration achieved with the methanesulfonate salt compared to the free-form drug (’208 Patent, Fig. 1).
  • Technical Importance: Developing a stable, consistently manufacturable, and highly bioavailable crystalline salt form is a crucial step in transforming a chemical compound into a safe and effective commercial drug product (’208 Patent, col. 1:33-40).

Key Claims at a Glance

The complaint asserts infringement of "one or more claims" of the '208 Patent (Compl. ¶46). Independent claim 1 is representative:

  • A crystalline form of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
  • wherein said crystalline compound is the hydrochloride of said compound, the hydrobromide of said compound, the p-toluenesulfonate of said compound, the sulfate of said compound, the methanesulfonate of said compound or the ethanesulfonate of said compound,
  • or the solvate of said salt.

U.S. Patent No. 10,407,393 - "High-Purity Quinoline Derivative and Method for Manufacturing Same"

  • Issued: September 10, 2019

The Invention Explained

  • Problem Addressed: The patent explains that prior art methods for producing the active ingredient, a quinoline derivative, result in the presence of impurities that are "difficult to remove" through common purification methods like chromatography and crystallization (’393 Patent, col. 4:1-6). One such impurity, compound (I), is noted as a potential mutagen, making its control critical (’393 Patent, col. 24:19-29).
  • The Patented Solution: The invention claims a highly pure composition of the quinoline derivative (or a salt thereof) characterized by a very low level of a specific impurity, compound (I). The patent claims compositions where this impurity is present at 350 parts per million (ppm) or less, and in some claims as low as 183 ppm or less (’393 Patent, Abstract; col. 5:1-5). The specification details manufacturing process modifications designed to achieve this level of purity (’393 Patent, col. 18:15-22:50).
  • Technical Importance: For pharmaceuticals, minimizing impurities, especially those that may be genotoxic, is a fundamental requirement for patient safety and for obtaining regulatory approval to market a drug product (’393 Patent, col. 24:23-29).

Key Claims at a Glance

The complaint asserts infringement of "one or more claims" of the ’393 Patent (Compl. ¶55). Independent claim 1 is representative:

  • A methanesulfonate salt of a compound represented by formula (IV),
  • wherein the content of a compound represented by formula (I) is 183 ppm by mass or less.

U.S. Patent No. 11,186,547 - "High-Purity Quinoline Derivative and Method for Manufacturing Same"

  • Patent Identification: U.S. Patent No. 11,186,547, "High-Purity Quinoline Derivative and Method for Manufacturing Same", issued November 30, 2021 (Compl. ¶35).
  • Technology Synopsis: This patent, related to the ’393 Patent, also addresses the problem of achieving high purity in the final lenvatinib drug product by controlling manufacturing byproducts (’547 Patent, col. 4:1-6). The invention claims compositions of the methanesulfonate salt of lenvatinib defined by low limits on specific impurities, such as impurity (A-1) at 60 ppm or less and impurity (I) at 183 ppm or less, ensuring the safety and quality of the final drug (’547 Patent, col. 6:28-33).
  • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶64). Independent claims 1, 2, and 3 are asserted.
  • Accused Features: The complaint alleges on information and belief that the generic lenvatinib mesylate in DRL's ANDA Products meets the specific purity limitations claimed in the patent (Compl. ¶65).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendants' generic "lenvatinib mesylate eq. 4 mg base and eq. 10 mg base oral capsules" for which approval is sought under ANDA No. 219300 (collectively, "DRL's ANDA Products") (Compl. ¶16).

Functionality and Market Context

DRL's ANDA Products are generic versions of Plaintiffs' branded drug LENVIMA®, an oral capsule therapy (Compl. ¶¶7, 30). LENVIMA® is a tyrosine kinase inhibitor approved by the FDA for treating various cancers, including differentiated thyroid cancer, renal cell carcinoma, hepatocellular carcinoma, and endometrial carcinoma (Compl. ¶31). The complaint alleges that Defendants intend to commercially manufacture, market, and sell these generic products in the United States upon receiving final FDA approval and prior to the expiration of the patents-in-suit (Compl. ¶¶16, 28). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed, element-by-element infringement analysis or include claim chart exhibits. The allegations are made generally and upon information and belief, pending discovery of Defendants’ confidential ANDA information and product samples (Compl. ¶¶40-42, 47).

The infringement theory for the ’208 Patent is that DRL's ANDA Products contain lenvatinib mesylate, which is one of the specific salt forms claimed, and that this salt exists in a "crystalline form" as required by the claims (Compl. ¶47). Infringement will depend on whether the particular crystalline structure, or polymorph, of the active ingredient in DRL's product falls within the scope of the patent's claims.

The infringement theory for the ’393 Patent and ’547 Patent is that DRL's ANDA Products contain the active ingredient lenvatinib mesylate at a level of purity that meets the patents' negative limitations (Compl. ¶¶56, 65). That is, the complaint alleges that the level of specific manufacturing impurities in DRL's product is below the parts-per-million thresholds recited in the asserted claims.

V. Key Claim Terms for Construction

The Term: "A crystalline form" (’208 Patent, Claim 1)

  • Context and Importance: This term is fundamental to the scope of the ’208 Patent. The dispute may center on whether the term covers any and all crystalline polymorphs of the claimed salts or is limited to the specific polymorphs disclosed in the specification (e.g., Form A, B, C). The infringement analysis will depend entirely on whether the specific crystalline structure of DRL's drug substance is encompassed by this term's construction.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The plain language of claim 1 recites "A crystalline form of... methanesulfonate," without specifying a particular polymorph, which may suggest the claim covers any crystalline version of that salt (’208 Patent, col. 45:60-67).
    • Evidence for a Narrower Interpretation: The specification provides detailed characterizations for specific crystalline forms, identified as Form A, Form B, etc., with distinct powder X-ray diffraction peaks and other physical data (’208 Patent, col. 2:15-67). A defendant may argue that the claims should be limited to these explicitly disclosed and characterized forms.

The Term: "content of a compound... is 183 ppm by mass or less" (’393 Patent, Claim 1)

  • Context and Importance: Practitioners may focus on this term because infringement of these purity patents hinges on analytical chemistry. The dispute will likely involve the methodology and sensitivity of the techniques (e.g., High-Performance Liquid Chromatography) used to measure the impurity levels. The term's construction could determine what analytical evidence is required to prove that the impurity content is at or below the claimed threshold.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim language does not specify a measurement technique, suggesting that any scientifically valid method capable of detecting the impurity at the claimed level could be used to demonstrate infringement.
    • Evidence for a Narrower Interpretation: The patent's detailed description discloses specific HPLC conditions for measuring impurities, including column type, mobile phase, and flow rate (’393 Patent, col. 31:10-44). A defendant may argue that infringement must be proven using the analytical methods disclosed in the patent, potentially excluding other techniques.

VI. Other Allegations

  • Indirect Infringement: The complaint includes allegations of induced and contributory infringement under 35 U.S.C. §§ 271(b) and (c) for all three patents (Compl. ¶¶49, 58, 67). The basis for these claims is the allegation that Defendants, by seeking FDA approval for their generic product with labeling that mirrors the approved uses for LENVIMA®, intend for and encourage doctors and patients to use the generic product in an infringing manner upon its launch.
  • Willful Infringement: The complaint does not contain an explicit allegation of willful infringement. The claims are predicated on the statutory act of infringement under 35 U.S.C. § 271(e)(2)(A), which is the submission of the ANDA.

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

  • A core issue will be one of polymorphic identity: Can Plaintiffs prove that the specific crystalline structure of the lenvatinib mesylate in Defendants' ANDA product is the same as one of the crystalline forms claimed in the ’208 patent, or will Defendants be able to demonstrate that their product utilizes a distinct, non-infringing polymorph?
  • A key evidentiary question will be one of analytical detection: Does the lenvatinib mesylate in Defendants' product meet the stringent purity thresholds of the ’393 and ’547 patents? This will likely evolve into a technical dispute over the validity, precision, and detection limits of the analytical methods used to measure impurities at the parts-per-million level.