DCT

1:17-cv-00213

Pfizer Inc v. Prinston Pharmaceutical Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00213, D. Del., 03/02/2017
  • Venue Allegations: Plaintiff alleges venue is proper as the suit arises from Defendant Prinston's filing of an Abbreviated New Drug Application (ANDA), an act of infringement alleged to cause foreseeable harm in Delaware. Jurisdiction is also asserted on the basis that several of the plaintiff and defendant entities are incorporated in Delaware.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an ANDA to market a generic version of the rheumatoid arthritis drug Xeljanz® constitutes an act of infringement of two patents covering the drug's active ingredient and its specific crystalline form.
  • Technical Context: The technology relates to pharmaceutical chemistry, specifically a small molecule compound that functions as a Janus Kinase (JAK) inhibitor and a stable crystalline polymorph of that compound suitable for oral tablet formulation.
  • Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act, triggered by Defendant Pfizer Inc v. Prinston Pharmaceutical Inc's submission of ANDA No. 209923. This ANDA contains a "Paragraph IV" certification alleging that Plaintiff's patents are invalid, unenforceable, or will not be infringed by the proposed generic product.

Case Timeline

Date Event
2001-05-31 Priority Date for U.S. Patent No. 7,301,023
2001-12-06 Priority Date for U.S. Patent No. 6,965,027
2005-11-15 U.S. Patent No. 6,965,027 Issued
2007-11-27 U.S. Patent No. 7,301,023 Issued
2017-01-16 Date of Defendant's Notice Letter regarding ANDA filing
2017-03-02 Complaint Filing Date

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

U.S. Patent No. 6,965,027 - “Crystalline 3-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile citrate”

  • Patent Identification: U.S. Patent No. 6,965,027, titled “Crystalline 3-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile citrate,” issued November 15, 2005 (the “’027 Patent”). (Compl. ¶29).

The Invention Explained

  • Problem Addressed: The patent addresses the need for a form of the compound tofacitinib citrate with physical properties suitable for pharmaceutical manufacturing. The background indicates that a specific crystalline form was found to possess "solid state properties which are acceptable to support tablet development" (’027 Patent, col. 3:52-56). This implies that other forms, such as amorphous material or other polymorphs, may have lacked the necessary stability or handling characteristics for large-scale production of a consistent drug product.
  • The Patented Solution: The invention is a specific, novel crystalline form of tofacitinib mono citrate salt. The patent characterizes this crystalline form through distinct physical data, including a specific X-ray powder diffraction (XRPD) pattern with characteristic peaks and a defined melting temperature range (’027 Patent, col. 3:7-13, FIG. 1, FIG. 2). This provides a stable, reproducible solid form of the active pharmaceutical ingredient.
  • Technical Importance: The identification and characterization of a single, stable crystalline polymorph is critical in drug development to ensure batch-to-batch consistency, predictable dissolution rates, bioavailability, and long-term stability of the final drug product (’027 Patent, col. 3:52-56).

Key Claims at a Glance

  • The complaint asserts infringement of at least claim 1 of the ’027 Patent (Compl. ¶44, ¶45).
  • The asserted independent claim is Claim 1, which consists of a single element:
    • A crystalline form of 3-{(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile mono citrate salt. (’027 Patent, col. 9:31-35).
  • The complaint alleges infringement of "one or more claims," suggesting dependent claims, which further define the crystalline form by its XRPD pattern or melting point, may also be asserted (Compl. ¶42).

U.S. Patent No. 7,301,023 - “Chiral Salt Resolution”

  • Patent Identification: U.S. Patent No. 7,301,023, titled “Chiral Salt Resolution,” issued November 27, 2007 (the “’023 Patent”). (Compl. ¶31).

The Invention Explained

  • Problem Addressed: Pharmaceutical compounds with chiral centers often exist as a mixture of stereoisomers (enantiomers), but frequently only one isomer provides the desired therapeutic effect while the other may be inactive or cause adverse effects. The patent’s background notes that for the class of compounds at issue, "individual enantiomers in substantially isolated pure form are preferred and at times required for drug use" (’023 Patent, col. 3:39-42). The problem, therefore, is the efficient separation of these stereoisomers from the racemic mixture produced during synthesis.
  • The Patented Solution: The patent discloses a method of "chiral salt resolution" to isolate the desired enantiomer of a precursor compound. This process involves using a specific stereoisomer of a resolving agent, such as tartaric acid, which selectively binds to one enantiomer in the mixture, causing it to precipitate from solution while the other remains dissolved, allowing for their separation (’023 Patent, col. 5:42-49). The patent was later corrected to claim the specific compound itself.
  • Technical Importance: Providing an effective method for chiral resolution is a crucial step in producing a stereochemically pure drug, which is often required for safety and efficacy by regulatory agencies.

Key Claims at a Glance

  • The complaint asserts infringement of claim 1 of the ’023 Patent (Compl. ¶48, ¶50).
  • A Certificate of Correction deleted the original claims and replaced them. The asserted independent claim is corrected Claim 1:
    • The compound 3-{(3R,4R)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile or a pharmaceutically acceptable salt thereof. (’023 Patent, Certificate of Correction, Feb. 17, 2009).
  • The complaint alleges infringement of "claim 1," implying a focus on this single, corrected claim (Compl. ¶48).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is "Prinston Generic Tablets," the proposed generic drug product that is the subject of Prinston Pharmaceutical Inc.'s ANDA No. 209923 (Compl. ¶13).
  • Functionality and Market Context: The Prinston Generic Tablets are alleged to contain "tofacitinib citrate as the active ingredient" and are intended to be a generic equivalent of Pfizer's Xeljanz® brand drug (Compl. ¶2, ¶35). The complaint identifies the active ingredient in Xeljanz® as the citrate salt of (3R,4R)-4-methyl-3-(methyl-7H-pyrrolo [2,3-d] pyrimidin-4-ylamino)-ß-oxo-1-piperidinepropanenitrile (Compl. ¶24). The filing of the ANDA seeking FDA approval to market this generic version prior to the expiration of the patents-in-suit is the statutorily defined act of infringement giving rise to the litigation (Compl. ¶2, ¶42, ¶48). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

’027 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A crystalline form of 3-{(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile mono citrate salt. The complaint alleges that Prinston's Generic Tablets, if approved and marketed, will contain tofacitinib citrate as the active ingredient and will thereby infringe the claim. The core allegation is that this ingredient will be the specific crystalline form claimed. ¶35, ¶44 col. 9:31-35
  • Identified Points of Contention:
    • Technical Question: The central dispute will be a factual one: does the tofacitinib citrate active pharmaceutical ingredient (API) in Prinston's ANDA product exist in the specific crystalline form claimed by the ’027 Patent? This will require comparing the physical properties of Prinston's API (e.g., its X-ray powder diffraction pattern) against the data disclosed in the patent specification.

’023 Patent Infringement Allegations

Claim Element (from Corrected Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
The compound 3-{(3R,4R)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile or a pharmaceutically acceptable salt thereof. The complaint alleges that the active ingredient in Prinston's Generic Tablets is "tofacitinib citrate" (¶35). It further provides the FDA-approved chemical name for tofacitinib, which explicitly identifies the (3R,4R) stereochemistry matching the compound recited in the claim (¶24). ¶24, ¶35, ¶50 col. 10:29-54; Certificate of Correction, p. 1
  • Identified Points of Contention:
    • Scope Question: A threshold issue is whether the "tofacitinib citrate" in Prinston's ANDA is, in fact, the citrate salt of the specific (3R,4R) compound claimed. As Prinston seeks approval for a generic version of Xeljanz®, which is defined by this stereochemistry, a finding of non-infringement on this basis seems unlikely unless Prinston can show its product contains a different, non-infringing isomer. The primary contention regarding this patent will likely concern its validity rather than the scope of infringement.

V. Key Claim Terms for Construction

For the ’027 Patent

  • The Term: "crystalline form"
  • Context and Importance: This term is the central limitation of claim 1. The infringement analysis will hinge entirely on whether Prinston's product meets the definition of this specific "crystalline form." Practitioners may focus on this term because the existence of different crystalline forms (polymorphs) of the same compound is common, and the case will turn on whether Prinston's form is the one claimed or a different, non-infringing one.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent states that the crystalline form exhibits a diffraction pattern with "characteristic peaks expressed in degrees 2-theta (2θ) at approximately 5.7, 16.1, 20.2 and 20.5" (’027 Patent, col. 3:11-13, emphasis added). The use of "approximately" and the identification of only four "characteristic" peaks out of many could support an argument that the claim covers forms with minor variations in their diffraction patterns.
    • Evidence for a Narrower Interpretation: The patent provides a detailed table (Table 1) listing numerous XRPD peaks to one decimal place and a specific procedure for collecting the data (’027 Patent, col. 9:1-8, col. 9:11-48). This detailed disclosure could support an argument that the "crystalline form" is narrowly defined by this comprehensive data set, and any product that does not substantially match this full pattern is a different polymorph outside the claim scope.

For the ’023 Patent

  • The terms in corrected claim 1 are a specific chemical name and the phrase "pharmaceutically acceptable salt thereof." These terms are defined by well-established conventions in organic chemistry and pharmaceutical science. As such, the claim is less likely to be the subject of a significant construction dispute compared to the factual question of whether Prinston's product is the claimed compound and the legal question of the claim's validity.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendant Zhejiang Huahai Pharmaceutical Co., Ltd. induced infringement by "actively and knowingly caus[ing] to be submitted, assist[ing] with, participat[ing] in, contribut[ing] to, and/or direct[ing] the submission" of the ANDA by Prinston, with knowledge of the patents-in-suit (Compl. ¶54).
  • Willful Infringement: While the complaint does not contain a formal count for "willful infringement," it lays the groundwork for such a claim. It alleges Prinston had "knowledge of the ’027 patent" and "knowledge of the ’023 patent" when it submitted its ANDA (Compl. ¶43, ¶49). Furthermore, the prayer for relief requests a judgment that the case is "exceptional" under 35 U.S.C. § 285, which could entitle Pfizer to an award of attorneys' fees (Compl., Prayer for Relief ¶E).

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

  • Polymorphic Identity: A core factual question will be one of physical form: does the active ingredient in Prinston's proposed generic product exhibit the specific physical and chemical characteristics of the "crystalline form" claimed in the ’027 patent? The outcome will likely depend on expert analysis of competing characterization data.
  • Validity: As foreshadowed by Prinston's Paragraph IV certification, a central legal issue will be the validity of the asserted claims. The key question for the court will be whether Prinston can prove by clear and convincing evidence that the claims covering the specific (3R,4R) compound (’023 Patent) or its specific crystalline form (’027 Patent) are invalid, for reasons such as obviousness or lack of enablement.
  • Infringement of the Compound: For the ’023 patent, the court must decide the threshold question of literal infringement: does Prinston's ANDA, by seeking to market a generic version of Xeljanz®, necessarily describe a product containing the specific (3R,4R) stereoisomer recited in corrected claim 1?