DCT

1:23-cv-00924

Pfizer Inc v. Zenara Pharma Pvt Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00924, D. Del., 08/23/2023
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant is a foreign corporation subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) for a generic version of the drug Vyndamax® constitutes an act of infringement of a patent covering a specific crystalline form of the active ingredient, tafamidis.
  • Technical Context: The technology concerns specific crystalline solid forms (polymorphs) of a small molecule drug, which can affect the drug's stability, manufacturability, and bioavailability.
  • Key Procedural History: The litigation was triggered under the Hatch-Waxman Act by a notice letter dated July 10, 2023, in which Zenara informed Pfizer of its ANDA filing. As part of that filing, Zenara made a "Paragraph IV" certification, asserting that U.S. Patent No. 9,770,441 is invalid, unenforceable, or will not be infringed by its proposed generic product.

Case Timeline

Date Event
2014-09-08 ’441 Patent Priority Date
2017-09-26 ’441 Patent Issue Date
2023-07-10 Zenara's ANDA Notice Letter to Pfizer
2023-08-23 Complaint Filing Date

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

  • Patent Identification: U.S. Patent No. 9,770,441 (“the ’441 Patent”), titled CRYSTALLINE SOLID FORMS OF 6-CARBOXY-2-(3,5-DICHLOROPHENYL)-BENZOXAZOLE, issued on September 26, 2017.

The Invention Explained

  • Problem Addressed: The patent's background explains that for a pharmaceutical compound, having a consistent and stable solid form is critical for manufacturing, clinical studies, and product stability ('441 Patent, col. 1:47-54). Different crystalline forms of the same chemical compound can have different physical properties, such as solubility and dissolution rates, which can impact a drug's effectiveness and safety ('441 Patent, col. 9:48-63).
  • The Patented Solution: The invention claims to solve this problem by identifying and characterizing specific, stable crystalline forms of the compound 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole (tafamidis) ('441 Patent, Abstract). These forms are defined by unique analytical signatures, such as specific peaks in a powder X-ray diffraction (PXRD) pattern, chemical shifts in a solid-state nuclear magnetic resonance (NMR) spectrum, or peaks in a Raman spectrum ('441 Patent, col. 2:6-15).
  • Technical Importance: By defining and claiming a specific crystalline form, the invention seeks to provide a drug substance with reliable and reproducible properties, which is essential for large-scale manufacturing and consistent therapeutic performance ('441 Patent, col. 9:48-55).

Key Claims at a Glance

  • The complaint asserts claims 1-16 (Compl. ¶31). The sole independent claim is Claim 1.
  • Claim 1 is directed to:
    • A crystalline form of 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole,
    • wherein the crystalline form has an analytical parameter selected from a Markush group consisting of:
      • a solid state NMR spectrum comprising 13C chemical shifts (ppm) at 120.8±0.2 and 127.7±0.2, OR
      • a powder X-ray diffraction pattern comprising a peak at a diffraction angle (20) of 28.6°±0.2, OR
      • a Raman spectrum comprising a Raman shift peak (cm-1) at 1292±2.
  • The complaint reserves the right to assert dependent claims 2-16, which add further analytical parameters to narrow the definition of the crystalline form (Compl. ¶31).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is "Zenara's ANDA Product," a proposed generic version of Vyndamax® containing 61 mg of tafamidis in capsule form (Compl. ¶1-2).

Functionality and Market Context

The product is intended for the treatment of "the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization" (Compl. ¶16). The complaint alleges that Zenara's submission of its ANDA (No. 218205) to the FDA is an act of infringement, as it seeks approval to market this generic drug prior to the expiration of the ’441 Patent (Compl. ¶1-2, ¶35).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint. The infringement allegations are made on "information and belief" pending discovery of the contents of Zenara's confidential ANDA submission (Compl. ¶31).

’441 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A crystalline form of 6-carboxy-2-(3,5-dichlorophenyl)-benzoxazole... The complaint alleges that Zenara's ANDA Product contains tafamidis, which is the same chemical compound. ¶33 col. 1:16-25
...wherein said crystalline form has an analytical parameter selected from the group consisting of a solid state NMR spectrum comprising 13C chemical shifts (ppm) at 120.8±0.2 and 127.7±0.2, a powder X-ray diffraction pattern comprising a peak at a diffraction angle (20) of 28.6°±0.2, and a Raman spectrum comprising a Raman shift peak (cm-1) at 1292±2. The complaint alleges on information and belief that Zenara's ANDA product is a crystalline form that meets at least one of the specified analytical parameters. The complaint does not provide specific data from the accused product. ¶31, ¶37 col. 23:6-14
  • Identified Points of Contention:
    • Evidentiary Question: The central issue is factual: does Zenara's proposed generic product actually possess the specific crystalline structure defined by the analytical parameters of Claim 1? The complaint pleads infringement on "information and belief," and the case will depend on whether technical data from Zenara's ANDA, once produced in discovery, shows a crystalline form that falls within the claimed parameters.
    • Scope Questions: A likely point of dispute will be the scope of the term "±0.2" as applied to the PXRD and NMR peak measurements and "±2" for the Raman peak measurement. The parties may contest whether the measured values for Zenara's product fall within these claimed ranges, considering inherent instrumental variability.

V. Key Claim Terms for Construction

  • The Term: "a powder X-ray diffraction pattern comprising a peak at a diffraction angle (20) of 28.6°±0.2" (and the analogous NMR and Raman limitations).
  • Context and Importance: Infringement will be determined by a direct comparison of the analytical data for Zenara's product against the numerical ranges recited in the claim. The construction of the tolerance "±0.2" is therefore dispositive, as it defines the literal boundary of the claim.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification explicitly acknowledges experimental variability, stating that "one skilled in the art will appreciate that the peak positions (20) will show some variability, typically as much as 0.1 to 0.2 degrees" ('441 Patent, col. 11:33-39). Plaintiffs may argue this passage defines the term as encompassing known and expected instrumental variations.
    • Evidence for a Narrower Interpretation: A defendant may argue that the patentee defined the invention with a specific numerical precision and should be held to it. The patent also provides specific examples and figures (e.g., FIG. 2, listing a peak at 28.6) that could be used to argue the claim is tied to the specific "Form 1" polymorph disclosed, with the tolerance meant to cover only minor deviations from that exact form, not a broader range of different structures.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement, stating that Zenara's proposed product labeling will direct and encourage physicians and patients to use the ANDA product in an infringing manner (i.e., for the patented method of treating transthyretin amyloid disease) (Compl. ¶34, ¶39). Contributory infringement is also alleged on the basis that the product is not a staple article and is not suitable for substantial non-infringing use (Compl. ¶40).
  • Willful Infringement: The complaint alleges that Zenara has acted with "full knowledge of the '441 patent and without a reasonable basis for believing that it would not be liable for infringement" (Compl. ¶43). This allegation is based on Zenara's Paragraph IV certification, which demonstrates pre-suit knowledge of the patent, and the listing of the ’441 patent in the FDA's Orange Book in connection with Vyndamax® (Compl. ¶27, ¶30).

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

  • A primary issue will be one of evidence: Does the characterization data within Zenara's confidential ANDA filing, or data from samples of its product, show that its crystalline form of tafamidis exhibits the specific PXRD, NMR, or Raman peaks required by Claim 1 of the ’441 Patent? The outcome will depend entirely on a comparison of technical data.
  • A second core issue will be one of claim construction: How should the court define the scope of the numerical tolerances, such as "±0.2," in the claim limitations? The resolution of this question will set the boundaries for the infringement analysis and could be dispositive if Zenara's product characteristics fall near the edges of the claimed ranges.
  • A third major battleground will be validity: As indicated by its Paragraph IV certification, Zenara will likely challenge the validity of the ’441 Patent (Compl. ¶30). This defense may question whether the claimed crystalline form was truly new and non-obvious over the prior art related to tafamidis, or whether the patent adequately describes and enables one skilled in the art to make and use the claimed form.