Pfizer Inc v. Zydus Pharma USA Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Pfizer Inc. (Delaware); Warner-Lambert Company LLC (Delaware); PF Prism Imb BV. (Netherlands)
  • Defendant: Zydus Pharmaceuticals (USA) Inc. (New Jersey); Zydus Worldwide DMCC (United Arab Emirates); Cadila Healthcare, Ltd. (India)
  • Plaintiff’s Counsel: Williams & Connolly LLP; Gibbons P.C.
• Case Identification: 1:20-cv-14580, D.N.J., 10/16/2020
• Venue Allegations: Venue is based on Defendant Zydus Pharmaceuticals (USA) Inc. being a New Jersey corporation with its principal place of business in the state, thereby consenting to jurisdiction. The other Zydus entities are alleged to be subject to jurisdiction through their business activities directed at New Jersey.
• Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the cancer drug IBRANCE® (palbociclib) constitutes an act of infringement of a patent covering a specific crystalline form of the active pharmaceutical ingredient.
• Technical Context: The technology concerns the specific solid-state chemical properties (polymorphism and particle size) of a drug compound, which are critical for ensuring stable, consistent, and effective manufacturing of an oral medication.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act following a notice letter dated September 11, 2020, in which Zydus informed Pfizer of its ANDA filing and its certification that the patent-in-suit is invalid, unenforceable, or will not be infringed by its proposed generic product.

Case Timeline

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

U.S. Patent No. 10,723,730 - "Solid Forms of a Selective Cdk4/6 Inhibitor"

• Patent Identification: U.S. Patent No. 10723730, "Solid Forms of a Selective Cdk4/6 Inhibitor," issued July 28, 2020. (Compl. ¶21).

The Invention Explained

• Problem Addressed: The patent's background section explains that the free base of the active compound, palbociclib, when produced by traditional methods, was "highly static prone and formed small primary particles, which agglomerated into large, hard agglomerates" that were unsuitable for pharmaceutical development and manufacturing. (’730 Patent, col. 2:3-9).
• The Patented Solution: The invention is a specific crystalline form of the palbociclib free base (polymorph Form A) that has a larger primary particle size. This form exhibits "improved physicochemical and manufacturability properties," overcoming the agglomeration and handling issues of previously known forms. (’730 Patent, col. 2:9-12). The claims define this improved form by its specific powder X-ray diffraction (PXRD) pattern and particular particle size distributions.
• Technical Importance: By providing a form of the active pharmaceutical ingredient with controlled particle size and improved physical properties, the invention enables reliable and efficient large-scale manufacturing of the final drug product. (’730 Patent, col. 17:15-24).

Key Claims at a Glance

• The complaint asserts independent claims 1, 7, and 15. (Compl. ¶¶ 28, 30, 32). The complaint states that Zydus's product is covered by "one or more claims," reserving the right to assert others. (Compl. ¶26).
• Independent Claim 1:
  • A crystalline free base of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one (palbociclib);
  • Having a powder X-ray diffraction (PXRD) pattern with peaks at specific angles (8.0±0.2, 10.1±0.2, and 11.5±0.2); and
  • Having a primary particle size distribution characterized by a D90 value of from about 30 µm to about 65 µm.
• Independent Claim 7:
  • A crystalline free base of palbociclib;
  • Having a PXRD pattern with the same specific peaks as claim 1; and
  • Having a volume mean diameter (D[4,3]) of from about 15 µm to about 40 µm.
• Independent Claim 15:
  • A crystalline free base of palbociclib;
  • Having a PXRD pattern with the same specific peaks as claim 1; and
  • Having a volume mean diameter (D[4,3]) of from about 15 µm to about 30 µm.

III. The Accused Instrumentality

• Product Identification: The accused instrumentality is "Zydus’s ANDA Product," defined as generic palbociclib capsules in 75 mg, 100 mg, and 125 mg dosages, for which Zydus seeks FDA approval via ANDA No. 213098. (Compl. ¶2).
• Functionality and Market Context:
  • The complaint alleges on information and belief that the active pharmaceutical ingredient (API) in Zydus's ANDA Product is a crystalline free base of palbociclib. (Compl. ¶28).
  • The core of the infringement allegation is that this API possesses the specific physical characteristics—namely the crystalline structure identified by PXRD peaks and the particle size distributions—recited in the asserted claims of the ’730 patent. (Compl. ¶¶ 28, 30, 32).
  • The product is a proposed generic equivalent to Pfizer's branded drug IBRANCE®, a treatment for certain types of breast cancer, and would compete directly with it in the market. (Compl. ¶1).
• No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart exhibit. The infringement theory is based on the allegation that Zydus's ANDA product necessarily meets the limitations of the asserted claims.

'730 Patent Infringement Allegations

• Identified Points of Contention:
  • Evidentiary Question: The complaint's allegations are made "on information and belief," as is typical before discovery in an ANDA case. The central factual dispute will be whether the API described in Zydus's confidential ANDA submission actually possesses the specific PXRD pattern and particle size characteristics required by the claims.
  • Technical Question: The case will involve detailed analysis of analytical chemistry data (e.g., PXRD, laser diffraction for particle sizing). A key question for the court will be whether the data for Zydus's product falls squarely within the claimed parameters, or if it lies at the boundaries, raising questions of measurement error and claim scope.

V. Key Claim Terms for Construction

• The Term: "about"
• Context and Importance: This term appears in the numerical limitations for both the PXRD peak locations (e.g., "8.0±0.2") and the particle size ranges (e.g., "from about 30 µm to about 65 µm"). Its construction is critical because it defines the permissible boundaries of the claims. Whether Zydus's product literally infringes could turn on the degree of variability this term allows. Practitioners may focus on this term because the patent claims multiple, distinct, and narrow particle size ranges, making the dividing line between them a central issue.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The specification provides an explicit definition, stating the term "about" means "within a statistically meaningful range of a value, such as a stated concentration range, time frame, molecular weight, particle size, temperature or pH." (’730 Patent, col. 3:66-4:1). This language may support an interpretation that allows for standard experimental variance.
  • Evidence for a Narrower Interpretation: The patent claims several distinct particle size ranges across its independent claims (e.g., Claim 1 claims D90 of "about 30 µm to about 65 µm," while Claim 7 claims a different metric, D[4,3], of "about 15 µm to about 40 µm"). An argument could be made that the term "about" should not be construed so broadly as to cause these deliberately distinct ranges to significantly overlap or render the specific endpoints meaningless.

VI. Other Allegations

• Indirect Infringement: The complaint alleges active inducement based on Zydus's intent to market its ANDA product upon approval with knowledge of the ’730 patent. (Compl. ¶37). It also pleads contributory infringement, alleging the ANDA product is not a staple article of commerce and is not suitable for substantial noninfringing use. (Compl. ¶38). The statutory basis for the infringement claim is Zydus's submission of the ANDA itself under 35 U.S.C. § 271(e)(2). (Compl. ¶33).
• Willful Infringement: Willfulness is alleged based on Zydus having "full knowledge of the '730 patent," evidenced by its Paragraph IV certification letter, and proceeding "without a reasonable basis for believing that it would not be liable for infringement." (Compl. ¶41).

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

• A central issue will be one of evidentiary proof: does the API in Zydus's ANDA, as revealed in discovery, factually exhibit the specific combination of crystalline form (defined by PXRD peaks) and particle size distribution (defined by D90 or D[4,3] values) that is recited in the asserted claims?
• A key legal question will be one of claim scope: how will the court construe the term "about" as it applies to the precise numerical ranges in the claims? The outcome of the infringement analysis may hinge on whether this term permits minor deviations from the stated values, a determination that could be influenced by the multiple, distinct ranges claimed in the patent.