DCT

2:20-cv-20270

Eagle Pharma Inc v. Shipla Medicare Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:20-cv-20270, D.N.J., 12/23/2020
  • Venue Allegations: Venue is alleged to be proper in any judicial district as the defendant is a foreign corporation. The complaint further alleges that the defendant develops and distributes drug products for sale throughout the United States, including within the District of New Jersey, and has previously consented to jurisdiction in the district in other matters.
  • Core Dispute: Plaintiffs allege that Defendant's submission of a New Drug Application to the FDA for its generic Pemetrexed Injection products constitutes an act of infringement of a patent directed to a specific crystalline form of pemetrexed diacid, a precursor to the active drug.
  • Technical Context: The lawsuit operates in the field of pharmaceutical polymorphs, where distinct crystalline structures of a drug substance can have significant implications for a product's stability, manufacturability, and therapeutic performance.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiffs' receipt of a Paragraph IV notice letter from the Defendant. The complaint states it was filed within the statutory 45-day window, which typically triggers a 30-month stay on FDA approval of the generic product. The Defendant's notice letter allegedly asserted non-infringement but did not challenge the validity of the patent-in-suit.

Case Timeline

Date Event
2014-10-30 '990 Patent Priority Date
2017-03-28 '990 Patent Issue Date
2020-12-23 Complaint Filing Date

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

U.S. Patent No. 9,604,990 - “Crystalline forms of pemetrexed diacid and manufacturing processes therefor,” issued March 28, 2017

The Invention Explained

  • Problem Addressed: The patent's background section describes various previously known crystalline forms of pemetrexed diacid, a crucial precursor for the chemotherapy drug pemetrexed. These prior art forms are described as having "inevitable shortcoming[s]," such as being difficult to filter, requiring long crystallization times, incorporating hard-to-remove solvents, or necessitating high-temperature drying that could risk chemical degradation ('990 Patent, col. 2:2-52).
  • The Patented Solution: The invention claims to solve these problems by providing two "novel crystalline forms of pemetrexed diacid" (designated Form 1 and Form 2) that are described as stable, possessing good crystallinity, and suitable for large-scale manufacturing with high yields under mild conditions ('990 Patent, col. 2:56-59; col. 5:6-14). The patent primarily uses powder X-ray diffraction (PXRD) data to define and distinguish these new forms ('990 Patent, Abstract).
  • Technical Importance: The development of stable and easily manufacturable polymorphs is important in the pharmaceutical industry for ensuring consistent product quality, improving shelf-life, and enabling cost-effective, large-scale production of drug substances ('990 Patent, col. 1:39-43; col. 2:53-59).

Key Claims at a Glance

  • The complaint asserts infringement of "at least one claim" without specifying which ones (Compl. ¶24). All granted claims in the '990 Patent are directed to "crystalline Form 2" or a process for making it. Independent claim 1 is a composition of matter claim.
  • Independent Claim 1 recites:
    • A crystalline Form 2 of pemetrexed diacid,
    • characterized by a powder X-ray diffraction pattern with peaks at about 9.0, 12.7, 14.4, 16.3 and 25.3±0.2 degrees two-theta,
    • wherein the crystalline Form 2 is substantially free of other crystalline forms of pemetrexed diacid.
  • The complaint implicitly reserves the right to assert other claims, including dependent claims that further define the properties of Form 2, such as additional PXRD peaks, weight loss characteristics measured by TGA, and specific purity levels ('990 Patent, claims 2-6, 12-15).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are Defendant Shilpa's "Pemetrexed Injection, 100 mg/10 mL, 500 mg/50 mL and 1 g/100 mL," as described in its New Drug Application (NDA) No. 215179 ("the Shilpa NDA Products") (Compl. ¶¶ 1, 20).

Functionality and Market Context

  • The Shilpa NDA Products are proposed generic injectable chemotherapy drugs (Compl. ¶¶ 1, 5). The complaint alleges these products are generic versions of Plaintiff Eagle's branded PEMFEXY® product and are intended for distribution and sale throughout the United States upon receiving FDA approval (Compl. ¶¶ 5, 10, 21). The complaint does not contain specific allegations regarding the crystalline form of the pemetrexed diacid used in the manufacture of the final drug product, as this information is typically contained within the confidential NDA.

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or a detailed, element-by-element analysis of infringement. The infringement allegations are based on the statutory act of submitting the Shilpa NDA, which Plaintiffs contend seeks approval for a product that, if commercially manufactured and sold, would necessarily infringe the '990 Patent (Compl. ¶24). No probative visual evidence provided in complaint.

Identified Points of Contention

  • Evidentiary Question: The central issue will be a factual one: what is the actual crystalline structure of the pemetrexed diacid that will be used to manufacture the Shilpa NDA Products? The complaint does not, and likely cannot, provide this evidence, as it is contained within the confidential NDA filing that will be subject to discovery. The dispute will turn on whether that material exhibits the PXRD pattern claimed for Form 2.
  • Scope Questions: A likely point of dispute will be the interpretation of the claim term "substantially free of other crystalline forms." The patent specification provides a tiered definition for this term ('990 Patent, col. 5:28-32), and the parties may contest which level of purity is required to meet the limitation. A second question relates to the scope of the term "about" as applied to the PXRD peak locations, which could be critical if Shilpa's product exhibits peaks close to, but not exactly matching, the recited values.

V. Key Claim Terms for Construction

The Term: "substantially free of other crystalline forms of pemetrexed diacid"

Context and Importance

  • This term from independent claim 1 defines the required purity of the claimed polymorph. The infringement analysis will depend on whether Shilpa's product, as described in its NDA, meets this negative limitation. Practitioners may focus on this term because the level of polymorph purity can be a critical distinguishing feature in pharmaceutical patents.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The specification provides an explicit definition that could support a broader reading: "'substantially free' refers to an amount of 10% or less of another form" ('990 Patent, col. 5:28-30). Dependent claim 12 also claims this 10% threshold explicitly ('990 Patent, col. 12:12-14).
  • Evidence for a Narrower Interpretation: The same sentence in the specification immediately provides a series of preferred, narrower definitions: "preferably 8%, 5%, 4%, 3%, 2%, 1%, 0.5%, or less of another form" ('990 Patent, col. 5:30-32). A party could argue that these preferences, along with dependent claims 13-15 which claim purity levels of 5%, 3%, and 1% respectively, suggest that a person of ordinary skill would understand the invention to be directed toward higher-purity forms.

The Term: "about" (in "peaks at about 9.0...")

Context and Importance

  • This term's construction is central to determining the boundaries of literal infringement for the PXRD peak values. The scope of "about" dictates how much deviation from the recited values is permissible while still falling within the claim.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: A party arguing for a broader scope may contend that "about" is intended to encompass the normal range of experimental variability inherent in PXRD analysis, as would be understood by a skilled artisan.
  • Evidence for a Narrower Interpretation: The claim language itself provides a potential definition. The list of peaks concludes with the modifier "±0.2 degrees two-theta" ('990 Patent, col. 8:67-col. 9:1). A party could argue this provides an explicit, and therefore limiting, definition for the scope of "about" throughout the claim.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges both induced and contributory infringement should the Shilpa NDA be approved (Compl. ¶¶ 28-31). The inducement allegation is based on Shilpa's alleged knowledge of the '990 Patent and its intent for infringement to occur via "promotional activities and package inserts" (Compl. ¶30). The contributory infringement allegation is based on the assertion that the Shilpa NDA Products are "especially made or adapted for use in infringing" the '990 Patent and are not staple articles of commerce with substantial noninfringing uses (Compl. ¶28).

Willful Infringement

  • The complaint does not use the term "willful infringement" but does allege that the case is "exceptional" under 35 U.S.C. § 285, which would warrant an award of attorneys' fees (Compl. ¶33). This allegation is predicated on Shilpa's alleged knowledge of the '990 Patent (Compl. ¶30).

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

  • A core issue will be one of evidentiary proof: does the pemetrexed diacid described in Shilpa's confidential New Drug Application, and which will be used to manufacture its proposed product, in fact possess the specific crystalline structure of "Form 2" as defined by the characteristic powder X-ray diffraction peaks recited in the '990 Patent claims?
  • A key legal question will be one of definitional scope: assuming Shilpa’s product is found to contain the patented Form 2, does it meet the claimed purity threshold of being "substantially free" of other polymorphic forms? The outcome may depend on how the court construes this term in light of the tiered definitions provided in the patent's specification.