DCT

1:18-cv-00795

Pfizer Inc v. Apotex Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-00795, D. Del., 05/25/2018
  • Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware because Defendants transact business in the state, have purposefully availed themselves of the forum by engaging in prior litigation there, and filed an Abbreviated New Drug Application (ANDA) seeking approval to sell the accused product throughout the United States, including in Delaware.
  • Core Dispute: Plaintiff alleges that Defendant's filing of an ANDA to market a generic version of the cancer drug Inlyta® constitutes an act of infringement of a patent claiming a specific crystalline form of the active ingredient, axitinib.
  • Technical Context: The lawsuit centers on pharmaceutical polymorphs—distinct crystalline structures of the same chemical compound—which can have different physical properties critical for drug formulation, stability, and bioavailability.
  • Key Procedural History: This is a Hatch-Waxman Act litigation initiated in response to Defendant's submission of an ANDA containing a "Paragraph IV certification," which asserts that Plaintiff's patent is invalid, unenforceable, and/or will not be infringed by the proposed generic product.

Case Timeline

Date Event
2007-04-05 '140 Patent Priority Date
2012-01-27 Pfizer's Inlyta® (axitinib) approved by FDA
2014-07-29 U.S. Patent No. 8,791,140 Issued
2018-04-12 Apotex sends Paragraph IV Notice Letter to Pfizer
2018-05-25 Complaint Filing Date

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

U.S. Patent No. 8,791,140 - "Crystalline Forms of 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyondazole Suitable for the Treatment of Abnormal Cell Growth in Mammals"

  • Issued: July 29, 2014

The Invention Explained

  • Problem Addressed: The patent's background explains that a single pharmaceutical compound can exist in multiple solid-state forms, known as polymorphs, which possess different physical properties ('140 Patent, col. 2:19-21). This variability can be problematic for manufacturing and formulation, as properties like stability, solubility, and flow are critical for producing a consistent and reliable drug product ('140 Patent, col. 2:15-19, col. 2:32-36).
  • The Patented Solution: The invention identifies and characterizes novel, stable crystalline forms of the active pharmaceutical ingredient axitinib (referred to as "Compound 1") ('140 Patent, col. 2:56-65). The patent claims specific polymorphs by defining their unique structural fingerprints, primarily through characteristic peaks in a powder X-ray diffraction (PXRD) pattern, as illustrated in figures such as FIG. 6 ('140 Patent, col. 4:50-53, FIG. 6).
  • Technical Importance: Identifying and patenting a specific, advantageous polymorph of a drug allows for greater control over the drug product's quality and performance and can provide market exclusivity beyond the life of the original compound patent.

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims, identifying independent claim 1 as an example (Compl. ¶39-40).
  • Claim 1 requires:
    • A crystalline form of 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole,
    • wherein said crystalline form has a powder X-ray diffraction pattern comprising a peak at diffraction angle (2θ) of 6.0±0.1,
    • and further comprising at least one peak at diffraction angle (2θ) selected from 11.5±0.1, 21.0±0.1 and 26.9±0.1.
  • The complaint notes that Plaintiff may assert other claims from the '140 patent (Compl. ¶39).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Apotex’s generic axitinib tablets (1 mg and 5 mg), for which Apotex seeks FDA approval through ANDA No. 211650 (Compl. ¶1, ¶29).

Functionality and Market Context

The accused product is a generic version of Pfizer’s branded drug, Inlyta®, which is approved for the treatment of advanced renal cell carcinoma (Compl. ¶25). The complaint alleges, upon information and belief, that the active pharmaceutical ingredient in Apotex's proposed product is the specific crystalline form of axitinib covered by the '140 patent (Compl. ¶34, ¶41). Apotex's ANDA filing is a direct commercial challenge aimed at marketing a lower-cost generic equivalent to Pfizer's product prior to the expiration of the '140 patent (Compl. ¶1). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
a crystalline form of 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole, The complaint alleges on information and belief that Apotex's ANDA Product contains a crystalline form of axitinib. ¶40-41 col. 1:30-45
wherein said crystalline form has a powder X-ray diffraction pattern comprising a peak at diffraction angle (2θ) of 6.0±0.1 The complaint alleges on information and belief that the crystalline form in Apotex's ANDA Product exhibits a PXRD pattern meeting this limitation. ¶40-41 col. 4:50-62
and further comprising at least one peak at diffraction angle (2θ) selected from 11.5±0.1, 21.0±0.1 and 26.9±0.1 The complaint alleges on information and belief that the crystalline form in Apotex's ANDA Product exhibits a PXRD pattern with at least one of these additional required peaks. ¶40-41 col. 4:50-62

Identified Points of Contention

  • Technical Question: The central factual dispute will be whether the crystalline form of axitinib in Apotex's ANDA product actually exhibits the PXRD peak pattern recited in claim 1. The complaint is based on "information and belief" and notes that the parties were unable to agree on terms for Pfizer to review Apotex's ANDA, samples, and data (Compl. ¶33). This raises the evidentiary question of what physical characterization data for the accused product will show.
  • Scope Question: A potential legal dispute concerns the interpretation of the numerical tolerance "±0.1" degrees 2θ. The case may raise the question of how this explicit tolerance interacts with the patent’s more general disclosure that PXRD peak positions can have instrumental variability of "typically as much as 0.1 to 0.2 degrees" ('140 Patent, col. 12:30-36).

V. Key Claim Terms for Construction

  • The Term: "a powder X-ray diffraction pattern comprising a peak at diffraction angle (2θ) of [value]±0.1"
  • Context and Importance: This phrase is the primary feature used to define and distinguish the patented polymorph from other forms of the same compound. The entire infringement analysis will depend on whether the measured PXRD peaks from Apotex's product fall within the claimed numerical ranges. Practitioners may focus on this term because its construction will determine the literal boundaries of the claim.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification contains language that could support a more flexible reading of the claimed ranges. It states that "one skilled in the art will appreciate that the peak positions (2θ) will show some variability, typically as much as 0.1 to 0.2 degrees" due to experimental and instrumental factors ('140 Patent, col. 12:30-36). A party could argue this context informs the meaning of "±0.1" and allows for slight deviations beyond the explicit range.
    • Evidence for a Narrower Interpretation: The claim language recites a specific numerical tolerance, "±0.1." A party could argue that the patentee deliberately chose this precise range to capture the invention and distinguish it from the prior art and other polymorphs disclosed in the patent, which have different peak values (e.g., '140 Patent, Table 1 vs. Table 4). This would suggest the "±0.1" boundary should be strictly applied.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Apotex will actively induce infringement upon FDA approval of its ANDA (Compl. ¶45). The basis for this allegation is that Apotex will "intentionally encourage acts of direct infringement... by others" (e.g., physicians and patients) by marketing the generic product with a label that instructs users to perform the patented method of treatment (Compl. ¶47).
  • Willful Infringement: The complaint alleges that Apotex acted with "full knowledge of the '140 patent" and "without a reasonable basis" for believing it would not be liable (Compl. ¶49). This allegation is based on Apotex's Paragraph IV certification and its notice letter to Pfizer, which establish pre-suit knowledge of the patent. Pfizer further alleges that the case is "exceptional" under 35 U.S.C. § 285, which would permit an award of attorneys' fees (Compl. ¶51).

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

  • A central issue will be one of evidentiary proof: Does the axitinib in Apotex's ANDA product, when subjected to powder X-ray diffraction analysis, produce a diffraction pattern that falls within the specific peak locations and tolerances recited in Claim 1? The resolution of this factual question will be determinative of literal infringement.
  • A key legal issue will be one of definitional precision: How will the court construe the claim term "±0.1" in the context of a technology where measurement variability is inherent? Whether this term is interpreted as a strict numerical boundary or as a range informed by the specification's broader discussion of instrumental error will be critical to defining the scope of the patent.