Keryx Biopharma Inc v. Par Pharmaceutical Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Keryx Biopharmaceuticals, Inc. (Delaware) and Panion & BF Biotech, Inc. (Taiwan)
  • Defendant: Par Pharmaceutical, Inc. (New York)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Wilmer Cutler Pickering Hale and Dorr LLP
• Case Identification: 1:19-cv-00955, D. Del., 05/23/2019
• Venue Allegations: Defendant Par Pharmaceutical, Inc. is alleged to have consented to jurisdiction and venue in the District of Delaware for the purposes of this action. The complaint further alleges that venue is proper based on Par's systematic and continuous business contacts within the state and its history of litigating in the district.
• Core Dispute: Plaintiffs allege that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the drug AURYXIA® infringes two patents related to pharmaceutical-grade ferric citrate and its tablet dosage forms.
• Technical Context: The technology concerns pharmaceutical compositions of ferric citrate, an iron-based medicine used to control high serum phosphorus levels (hyperphosphatemia) in adult patients with chronic kidney disease.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act, triggered by Defendant’s submission of ANDA No. 208217 and a Paragraph IV Certification alleging that Plaintiffs’ patents are invalid, unenforceable, or will not be infringed. The patents-in-suit are listed in the U.S. Food and Drug Administration's "Orange Book" for AURYXIA®. The complaint notes it was filed before the expiration of the statutory 45-day period following receipt of Defendant's notice letter, alleging that a dispute over the terms of confidential access to the ANDA materials necessitated the early filing.

Case Timeline

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

U.S. Patent No. 8,093,423 - "Pharmaceutical-Grade Ferric Organic Compounds, Uses Thereof and Method of Making Same," issued January 10, 2012

The Invention Explained

• Problem Addressed: The patent describes a need for a commercially scalable manufacturing process for pharmaceutical-grade ferric citrate that can consistently produce a product meeting established quality standards, a challenge not met by prior art methods (’423 Patent, col. 1:63-col. 2:2).
• The Patented Solution: The invention provides a detailed manufacturing and quality control process for producing ferric citrate with specific properties, such as high solubility across a wide pH range and a large active surface area (’423 Patent, Abstract). The process involves specific steps for reacting precursor chemicals, washing the resulting precipitate, and controlling reaction parameters like pH and temperature to ensure the final product consistently meets pharmaceutical-grade specifications (’423 Patent, col. 2:26-50; Fig. 1).
• Technical Importance: This process enabled the reliable, large-scale production of a ferric citrate active pharmaceutical ingredient (API) with consistent physical properties, a critical step for developing a commercial drug product (’423 Patent, col. 2:17-25).

Key Claims at a Glance

• The complaint asserts one or more claims, identifying independent method claim 7 as an example (Compl. ¶25).
• Independent Claim 7 recites:
  • A method of reducing serum levels of phosphate in a subject,
  • the method comprising administering to the subject an effective amount of ferric citrate having an intrinsic dissolution rate between 1.88 and 4.0 mg/cm²/min to reduce serum levels of phosphate.
• The complaint reserves the right to assert other claims.

U.S. Patent No. 9,387,191 - "Ferric Citrate Dosage Forms," issued July 12, 2016

The Invention Explained

• Problem Addressed: The patent addresses the challenge of creating a stable and effective solid oral dosage form (tablet) of ferric citrate, noting that previous formulations were of "indefinite composition" and faced preparation difficulties (’191 Patent, col. 1:22-45).
• The Patented Solution: The invention discloses specific ferric citrate tablet formulations that include a high percentage of the active drug along with particular binders and lubricants. A key aspect of the solution is controlling the moisture content (measured as Loss on Drying, or LOD) during the granulation process to achieve tablets with desirable properties, such as high hardness, low friability, and consistent dissolution profiles (’191 Patent, Abstract; col. 3:9-14; col. 4:6-21).
• Technical Importance: The formulation technology allows for the manufacture of robust, high-drug-load ferric citrate tablets that disintegrate and dissolve reliably, which is essential for consistent therapeutic effect in patients.

Key Claims at a Glance

• The complaint asserts one or more claims, identifying independent claims 1, 6, 11, and 16 as examples (Compl. ¶33).
• Independent Claim 1 recites:
  • A ferric citrate tablet comprising:
  • (a) a core comprising approximately 90% to approximately 92% by weight of ferric citrate, approximately 4.5% to approximately 30% by weight of pregelatinized starch, and approximately 0.5% to approximately 3% by weight of a lubricant; and
  • (b) a coating,
  • wherein the tablet has a friability equal or less than 1% w/w,
  • and wherein at least 80% of the ferric citrate in the tablet is dissolved in less than or equal to 60 minutes as measured by test method USP <711>,
  • and the moisture content of the tablet is less than 10% by loss on drying (LOD).

III. The Accused Instrumentality

Product Identification

• The accused instrumentality is Defendant Par Pharmaceutical’s proposed generic version of AURYXIA® (Ferric Citrate) Tablets, for which it submitted ANDA No. 208217 to the FDA for marketing approval (Compl. ¶1).

Functionality and Market Context

• The proposed product is an oral, iron-based medicine designed to be a generic equivalent to AURYXIA® (Compl. ¶¶1, 7). Its intended uses are for the control of serum phosphorus levels in adult patients with chronic kidney disease on dialysis and for the treatment of iron deficiency anemia in adult patients with chronic kidney disease not on dialysis (Compl. ¶7). The complaint alleges that upon approval, Par intends to manufacture, import, and sell this product in the United States before the expiration of the patents-in-suit (Compl. ¶10).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain detailed infringement allegations or claim charts, stating that Plaintiffs had not been provided with the relevant portions of the ANDA at the time of filing (Compl. ¶22). The infringement theory is based on 35 U.S.C. § 271(e)(2)(A), where the submission of an ANDA for a drug claimed in a patent is an act of infringement. The allegations are premised on the legal requirement that the proposed generic product must be bioequivalent to the approved brand-name drug, AURYXIA®, which is covered by the patents-in-suit.

• ’423 Patent Infringement Allegations

• ’191 Patent Infringement Allegations

• Identified Points of Contention:
  • Technical Mismatch: The central dispute will be whether the product defined in Par’s ANDA meets every limitation of the asserted claims. For the ’423 patent, a key question is whether Par’s API possesses the specific "intrinsic dissolution rate" defined in claim 7. For the ’191 patent, disputes may arise over whether Par’s formulation falls within the specific weight percentage ranges and meets the quantitative thresholds for friability, dissolution, and moisture content.
  • Scope Questions: Since the complaint alleges infringement under the doctrine of equivalents, a potential point of contention is whether any differences between Par's product and the literal claim language are insubstantial. For instance, if Par uses a different binder than "pregelatinized starch," its equivalence will be a central issue.

V. Key Claim Terms for Construction

• Term: "intrinsic dissolution rate" (’423 Patent, Claim 7)

  • Context and Importance: This quantitative parameter is a cornerstone of the asserted claim of the ’423 patent. Infringement will depend entirely on whether Defendant's product is found to have a rate within the claimed numerical range. Practitioners may focus on this term because its precise measurement methodology could be a point of dispute.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party might argue that any standard, accepted method for measuring this rate is permissible unless explicitly disclaimed.
    • Evidence for a Narrower Interpretation: The patent specification provides a specific example of how this rate was determined, including the use of "solutions of pH 8" and specific experimental conditions (’423 Patent, Table 1, col. 11:1-col. 12:35). A party could argue these examples define and limit the proper method of measurement for claim construction purposes.

• Term: "approximately" (’191 Patent, Claim 1)

  • Context and Importance: This term modifies all the numerical ranges for the composition of the tablet core (e.g., "approximately 90% to approximately 92% by weight"). The scope of this term is critical, as it will determine whether a formulation that deviates slightly from the stated numbers still falls within the claim's literal scope.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party could argue that "approximately" should be given its ordinary meaning of "close to," affording a reasonable degree of numerical flexibility.
    • Evidence for a Narrower Interpretation: The patent provides numerous examples with precise formulations and performance data (’191 Patent, Tables 1-17). A party could argue that these specific embodiments constrain the meaning of "approximately," suggesting it does not encompass a wide range of deviation from the recited values.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that upon FDA approval, Par will induce infringement by encouraging healthcare providers and patients to use the proposed generic product in an infringing manner, with knowledge of the patents (’423 Patent, Compl. ¶27). It also alleges contributory infringement on the basis that Par's product is a material component of the patented methods, is especially adapted for infringement, and is not a staple commodity with substantial non-infringing uses (’423 Patent, Compl. ¶28). The prayer for relief seeks a judgment of direct, induced, and contributory infringement for all patents-in-suit (Compl. Prayer for Relief ¶E).
• Willful Infringement: The complaint does not contain a specific count for willful infringement. However, it alleges that Par was aware of the patents, at least as of its Paragraph IV certification (Compl. ¶21), and requests a finding that the case is "exceptional" and an award of attorneys' fees under 35 U.S.C. § 285 (Compl. ¶¶31, 38).

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

• An Evidentiary Question of Technical Compliance: As the complaint was filed without the benefit of discovery into Par's ANDA, the fundamental question for the litigation is factual: does the product specified in ANDA No. 208217 meet, on a limitation-by-limitation basis, the specific quantitative requirements of the asserted claims? This will turn on a detailed comparison of Par's confidential product specifications against the claimed dissolution rate ('423 patent) and the compositional and performance metrics ('191 patent).
• A Legal Question of Definitional Scope: A core legal issue will be the construction of the term "approximately" in the claims of the ’191 patent. The court's interpretation will determine the literal boundaries of the claimed compositional ranges, which may be decisive if Par’s formulation is designed to be similar, but not identical, to the patented AURYXIA® tablets.
• A Functional Question of Equivalence: Should literal infringement fail, the case will likely turn on the doctrine of equivalents. The key question will be whether any differences between Par’s proposed product and the patented invention—such as the use of alternative excipients or performance characteristics falling just outside the claimed numerical limits—are insubstantial from the perspective of one skilled in the art.