DCT

1:24-cv-07067

Eisai R&D Management Co Ltd v. Torrent Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-07067, D.N.J., 06/17/2024
  • Venue Allegations: Venue is alleged to be proper as Defendant is a foreign corporation subject to personal jurisdiction in New Jersey. Personal jurisdiction is asserted based on Defendant’s subsidiary having a principal place of business in New Jersey, Defendant’s business activities and contacts within the state, and its intent to market the accused generic products there.
  • Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) seeking FDA approval to market generic versions of Plaintiffs’ cancer drug LENVIMA® constitutes an act of infringement of three U.S. patents.
  • Technical Context: The technology concerns pharmaceutical compositions of lenvatinib, a tyrosine kinase inhibitor used in oncology, specifically claiming particular crystalline salt forms of the active ingredient and compositions with high purity levels.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s May 3, 2024, Paragraph IV Notice Letter, which certified that its proposed generic products would not infringe the patents-in-suit or that the patents are invalid. The patents-in-suit are listed in the FDA's "Orange Book" as covering LENVIMA®. The complaint notes that Plaintiffs have not been provided with Defendant's ANDA, as the parties did not reach an agreement on a Confidential Access Offer prior to the filing deadline.

Case Timeline

Date Event
2003-12-25 U.S. Patent No. 7,612,208 Priority Date
2009-11-03 U.S. Patent No. 7,612,208 Issued
2014-08-28 U.S. Patent No. 10,407,393 Priority Date
2014-08-28 U.S. Patent No. 11,186,547 Priority Date
2015-02-13 FDA Approves NDA for LENVIMA®
2019-09-10 U.S. Patent No. 10,407,393 Issued
2021-11-30 U.S. Patent No. 11,186,547 Issued
2024-05-03 Defendant Sends Paragraph IV Notice Letter
2024-06-17 Complaint Filed

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 (Compl. ¶19).

The Invention Explained

  • Problem Addressed: The patent addresses the need for forms of the active pharmaceutical ingredient (API) that possess high usability as a medicament and have superior physical properties and pharmacokinetics compared to the previously known free-form of the compound (’208 Patent, col. 1:29-41).
  • The Patented Solution: The invention provides specific crystalline salt forms of the API, including methanesulfonate, ethanesulfonate, hydrochloride, and others, as well as their solvates (’208 Patent, Abstract; col. 2:1-9). These specific solid-state forms are intended to offer improved characteristics, such as dissolution and bioavailability, which are critical for drug product performance (’208 Patent, Test Example 2).
  • Technical Importance: The selection of a specific salt and crystalline form is a critical step in pharmaceutical development, as it can significantly influence a drug's stability, manufacturability, and therapeutic efficacy.

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" without specification (Compl. ¶32, ¶35). 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 (Compl. ¶20).

The Invention Explained

  • Problem Addressed: Prior art methods for producing the quinoline derivative compound result in the formation of impurities that are difficult to remove using common purification techniques (’393 Patent, col. 3:1-9). One specific impurity, identified as Compound (I), is noted as a substance with "strong mutagenicity," making its control essential (’393 Patent, col. 23:20-28).
  • The Patented Solution: The invention provides the quinoline derivative compound (or a salt thereof) with a very low level of the specific impurity, Compound (I), namely 350 parts per million (ppm) by mass or less (’393 Patent, Abstract). The patent also discloses manufacturing methods designed to achieve this level of purity (’393 Patent, col. 17:15-20:47).
  • Technical Importance: Controlling genotoxic impurities to extremely low, parts-per-million levels is a significant challenge in pharmaceutical manufacturing and a critical requirement for regulatory approval.

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" without specification (Compl. ¶40, ¶43). Independent claim 1 is representative:
  • A compound represented by formula (IV) or a salt thereof,
  • wherein the content of a compound represented by formula (I) is 350 ppm by mass or less.

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

  • Issued: November 30, 2021 (Compl. ¶21).

The Invention Explained

  • Technology Synopsis: Continuing the work of the ’393 Patent, this patent further addresses impurities generated during the synthesis of the quinoline derivative (’547 Patent, col. 3:30-38). It claims the compound with specific, low levels of impurities, including a limit on Compound (I) of 183 ppm by mass or less (’547 Patent, Claim 1).
  • Asserted Claims: The complaint alleges infringement of "one or more claims" (Compl. ¶48). The patent contains independent claims 1-8.
  • Accused Features: The complaint alleges that the active pharmaceutical ingredient in Defendant’s proposed generic product will meet the specific purity limitations claimed in the patent (Compl. ¶49).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendant's proposed generic lenvatinib mesylate oral capsules, equivalent to 4 mg and 10 mg base, for which Torrent Ltd. seeks FDA approval via Abbreviated New Drug Application (ANDA) No. 219352 (Compl. ¶11, ¶23).

Functionality and Market Context

The products are generic versions of Plaintiffs' branded drug LENVIMA®, which is an oral medication approved for treating various cancers, including differentiated thyroid cancer, renal cell carcinoma, and hepatocellular carcinoma (Compl. ¶17). By filing an ANDA with a Paragraph IV certification, Torrent is seeking to market its generic product prior to the expiration of the patents-in-suit, which constitutes a statutory act of infringement under 35 U.S.C. § 271(e)(2) (Compl. ¶13, ¶32).

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed basis for its infringement allegations, as Plaintiffs had not received Defendant's ANDA submission prior to filing suit (Compl. ¶28). The allegations are made "upon information and belief" and are predicated on the statutory act of infringement created by the ANDA filing itself, which necessarily asserts that Torrent's product is the same as the branded LENVIMA® product covered by the patents-in-suit (Compl. ¶33, ¶41, ¶49).

  • Identified Points of Contention:
    • Scope Questions: A principal question for the '208 Patent will be one of structural identity: does the active pharmaceutical ingredient (API) in Torrent's ANDA product exist in one of the specific crystalline salt forms recited in the claims? For the ’393 and ’547 patents, the question will be one of quantitative scope: does Torrent’s API meet the parts-per-million purity limitations required by the asserted claims?
    • Technical Questions: The dispute will likely focus on analytical evidence. For the ’208 Patent, this may involve comparing X-ray powder diffraction (XRPD), infrared spectroscopy (IR), or other analytical data from Torrent's product with the data disclosed in the patent. For the ’393 and ’547 patents, the core technical question will be the measured concentration of impurities in Torrent's API, which may raise secondary questions about the appropriate analytical methods and their limits of detection.

No probative visual evidence provided in complaint.

V. Key Claim Terms for Construction

The complaint does not provide sufficient detail for analysis of claim construction disputes. However, based on the technology, certain terms may become central to the case.

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

  • Context and Importance: The entirety of the ’208 Patent's inventive concept rests on providing specific, stable crystalline salt forms. Practitioners may focus on this term because the scope of "crystalline" can be debated, particularly whether it permits minor amounts of amorphous material or requires perfect correspondence with the diffraction peaks disclosed in the patent’s figures (’208 Patent, Figs. 1-21).

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The claims use the general term "crystalline form" without specifying a degree of purity or requiring identity with a specific disclosed polymorph, which may support a construction that is not limited to a single, perfect crystal structure.
    • Evidence for a Narrower Interpretation: The specification provides detailed powder X-ray diffraction data and other analytical characterizations for multiple distinct crystalline forms (e.g., Form A, Form B, Form C) (’208 Patent, col. 2:10-54). A party may argue that "crystalline form" should be construed to mean one of these specifically identified and characterized polymorphs.

  • The Term: "content of...is 350 ppm by mass or less" (’393 Patent, Claim 1)

  • Context and Importance: This limitation defines the invention of the ’393 Patent. Infringement will be a direct quantitative measurement. Practitioners may focus on this term because disputes can arise over the methodology used to measure such low concentrations, including issues of accuracy, precision, and the limit of quantification of the analytical method.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: A party might argue that any scientifically valid method for measuring the impurity concentration is acceptable, as the claim does not recite a specific test method.
    • Evidence for a Narrower Interpretation: The patent specification describes detailed Liquid Chromatography (HPLC) methods for measuring the content of the specified impurity (’393 Patent, col. 31:9-34:24). A party may argue that this disclosed method is the proper standard for determining whether the claimed ppm limitation is met.

VI. Other Allegations

  • Indirect Infringement: The complaint includes conclusory allegations that if Defendant commercially manufactures, uses, or sells its ANDA product, it will induce or contribute to infringement by others (Compl. ¶37, ¶45, ¶53). No specific facts supporting knowledge or intent beyond the filing of the ANDA are provided.

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

  • A core issue will be one of structural and compositional identity: does the API in Torrent’s proposed generic product have the specific crystalline salt structure claimed by the ’208 patent, and does it meet the quantitative, parts-per-million purity limits required by the ’393 and ’547 patents? Resolution will depend on detailed analytical testing of Torrent’s product obtained through discovery.
  • A second central issue will be patent validity: can Plaintiffs establish that the claimed inventions are non-obvious? Defendant will likely argue that selecting a particular salt form from a known list of pharmaceutically acceptable salts (’208 Patent) or achieving a higher level of purity for a known compound (’393 and ’547 patents) would have been obvious to a person of ordinary skill in the art.