DCT

1:19-cv-00885

Keryx Biopharma Inc v. Watson Laboratories Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-00885, D. Del., 05/10/2019
  • Venue Allegations: Venue is alleged based on Teva USA's incorporation in Delaware and Watson's consent to venue in the district.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to market a generic version of AURYXIA® (Ferric Citrate) tablets constitutes an act of infringement of twelve patents related to novel forms of ferric citrate and methods of its use.
  • Technical Context: The technology concerns pharmaceutical compositions of ferric citrate used to treat hyperphosphatemia (elevated serum phosphate levels), a common and serious condition in patients with chronic kidney disease.
  • Key Procedural History: The complaint notes that Plaintiffs filed a related patent infringement action against Teva USA on December 19, 2018, arising from the submission of a different ANDA for a generic version of the same drug, AURYXIA®.

Case Timeline

Date Event
2003-02-19 Earliest Priority Date for all Patents-in-Suit
2010-08-03 U.S. Patent No. 7,767,851 Issues
2012-01-10 U.S. Patent No. 8,093,423 Issues
2012-10-30 U.S. Patent No. 8,299,298 Issues
2012-12-25 U.S. Patent No. 8,338,642 Issues
2013-12-17 U.S. Patent No. 8,609,896 Issues
2014-06-17 U.S. Patent No. 8,754,257 Issues
2014-06-17 U.S. Patent No. 8,754,258 Issues
2014-09-30 U.S. Patent No. 8,846,976 Issues
2014-12-02 U.S. Patent No. 8,901,349 Issues
2015-06-09 U.S. Patent No. 9,050,316 Issues
2016-05-03 U.S. Patent No. 9,328,133 Issues
2017-09-12 U.S. Patent No. 9,757,416 Issues
2018-12-19 Related action filed against Teva USA for a different ANDA
2019-04-01 Earliest date Teva sent Paragraph IV Certification Notice Letter
2019-05-10 Complaint Filed

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

U.S. Patent No. 7,767,851 - "Ferric Organic Compounds, Uses Thereof and Methods of Making Same"

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of treating hyperphosphatemia in renal failure patients with ferric citrate, noting that conventional crystalline forms of the compound have very slow dissolution rates, which necessitates administering substantially large oral doses. (’851 Patent, col. 1:36-62).
  • The Patented Solution: The invention provides a "novel form" of ferric citrate that is more soluble over a wider pH range and possesses a large active surface area. This is achieved through a specific synthesis method involving the formation of a polyiron oxo colloidal suspension and subsequent precipitation with an organic solvent, as outlined in the patent's general synthesis scheme. (’851 Patent, Abstract; col. 2:11-54; Fig. 1).
  • Technical Importance: A more soluble form of ferric citrate allows for a lower and more effective oral dose, which may improve patient compliance and reduce gastrointestinal side effects associated with large doses of iron-based compounds. (’851 Patent, col. 8:15-22).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶55).
  • Claim 1 of the ’851 Patent requires:
    • A solid form of ferric citrate
    • having a formula of C6H5O7Fe
    • and an intrinsic dissolution rate between 1.9 and 4.0 mg/cm²/min, as determined by the USP intrinsic dissolution assay in water,
    • wherein the solid form is synthesized by a five-step method involving forming a ferric hydroxide precipitate, creating a suspension, adding citric acid and heating, and precipitating the final product with an organic solvent.

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

The Invention Explained

  • Problem Addressed: The patent identifies a need for a scalable and consistent process to manufacture pharmaceutical-grade ferric citrate that complies with established quality specifications, a step beyond the initial discovery of a novel form. (’423 Patent, col. 1:64-col. 2:4).
  • The Patented Solution: The invention discloses a detailed manufacturing and quality control process for producing pharmaceutical-grade ferric citrate. The process includes specific steps for mixing reagents, controlling pH, washing precipitates, and using quality control (QC) checkpoints to ensure the final product meets release specifications for purity, composition, and impurity levels. (’423 Patent, Abstract; col. 2:26-51; Fig. 1).
  • Technical Importance: The patented solution provides a reliable, large-scale production method necessary for commercializing a pharmaceutical product, ensuring batch-to-batch consistency and compliance with regulatory standards. (’423 Patent, col. 2:18-25).

Key Claims at a Glance

  • The complaint asserts independent claim 7 (Compl. ¶62).

  • Claim 7 of the ’423 Patent requires:

    • A method of reducing serum levels of phosphate in a subject,
    • 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.

  • Multi-Patent Capsule: U.S. Patent No. 8,299,298, entitled "Pharmaceutical-Grade Ferric Organic Compounds, Uses Thereof and Method of Making Same," issued October 30, 2012.

    • Technology Synopsis: This patent claims a pharmaceutical composition comprising the novel form of ferric citrate with a specified BET active surface area (exceeding 16 sq. m/g) and a pharmaceutically suitable carrier. The invention focuses on the physical property of high surface area, which contributes to the enhanced dissolution rate and therapeutic efficacy.
    • Asserted Claims: Claim 1 (Compl. ¶70).
    • Accused Features: The accused feature is Defendants' proposed generic ferric citrate tablet (Compl. ¶70).

  • Multi-Patent Capsule: U.S. Patent No. 8,338,642, entitled "Ferric Organic Compounds, Uses Thereof and Methods of Making Same," issued December 25, 2012.

    • Technology Synopsis: This patent claims methods of treating hyperphosphatemia or metabolic acidosis by administering the specific form of ferric citrate having a BET active surface area greater than 16 sq. m/g. The claims are directed to the therapeutic application of the novel material form.
    • Asserted Claims: Claims 1, 8, 10, and 17 (Compl. ¶77).
    • Accused Features: The accused feature is the use of Defendants' proposed generic ferric citrate tablet as instructed by its labeling (Compl. ¶¶77, 80).

  • Multi-Patent Capsule: U.S. Patent No. 8,609,896, entitled "Ferric Organic Compounds, Uses Thereof and Methods of Making Same," issued December 17, 2013.

    • Technology Synopsis: This patent claims an orally administrable form of ferric citrate prepared from a form of ferric citrate that has an intrinsic dissolution rate of at least 1.88 mg/cm²/min. The claims focus on the final dosage form derived from the novel, highly soluble material.
    • Asserted Claims: Claim 1 (Compl. ¶86).
    • Accused Features: The accused feature is Defendants' proposed generic ferric citrate tablet (Compl. ¶86).

  • Multi-Patent Capsule: U.S. Patent No. 8,754,257, entitled "Pharmaceutical-Grade Ferric Organic Compounds, Uses Thereof and Method of Making Same," issued June 17, 2014.

    • Technology Synopsis: This patent claims a pharmaceutical composition comprising a form of ferric citrate with a specified intrinsic dissolution rate of 1.88-4.0 mg/cm²/min. The claims cover the composition itself, defined by the key functional property of the active ingredient.
    • Asserted Claims: Claim 1 (Compl. ¶93).
    • Accused Features: The accused feature is Defendants' proposed generic ferric citrate tablet (Compl. ¶93).

  • Multi-Patent Capsule: U.S. Patent No. 8,754,258, entitled "Ferric Organic Compounds, Uses Thereof and Methods of Making Same," issued June 17, 2014.

    • Technology Synopsis: This patent claims an orally administrable form of ferric citrate having a specified intrinsic dissolution rate. It is similar to other patents in the family but claims the final dosage form characterized by the novel dissolution property.
    • Asserted Claims: Claim 1 (Compl. ¶100).
    • Accused Features: The accused feature is Defendants' proposed generic ferric citrate tablet (Compl. ¶100).

  • Multi-Patent Capsule: U.S. Patent No. 8,846,976, entitled "Ferric Organic Compounds, Uses Thereof and Methods of Making Same," issued September 30, 2014.

    • Technology Synopsis: This patent claims a method of treating hyperphosphatemia by administering the orally administrable form of ferric citrate prepared from the material with the specified high dissolution rate. The claims are directed to the method of treatment using the final dosage form.
    • Asserted Claims: Claim 1 (Compl. ¶107).
    • Accused Features: The accused feature is the use of Defendants' proposed generic ferric citrate tablet as instructed by its labeling (Compl. ¶¶107, 109).

  • Multi-Patent Capsule: U.S. Patent No. 8,901,349, entitled "Ferric Organic Compounds, Uses Thereof and Methods of Making Same," issued December 2, 2014.

    • Technology Synopsis: This patent claims a method of treating hyperphosphatemia by administering a tablet comprising ferric citrate with a BET active surface area greater than 16 sq. m/g. This patent focuses on the specific tablet dosage form possessing the novel active ingredient.
    • Asserted Claims: Claim 1 (Compl. ¶115).
    • Accused Features: The accused feature is the use of Defendants' proposed generic ferric citrate tablet as instructed by its labeling (Compl. ¶¶115, 117).

  • Multi-Patent Capsule: U.S. Patent No. 9,050,316, entitled "Pharmaceutical-Grade Ferric Organic Compounds, Uses Thereof and Methods of Making Same," issued June 9, 2015.

    • Technology Synopsis: This patent claims methods of treating metabolic acidosis by administering tablets of the novel ferric citrate. It expands the protected methods of use beyond hyperphosphatemia to include metabolic acidosis, another common condition in renal failure patients.
    • Asserted Claims: Claims 1 and 12 (Compl. ¶123).
    • Accused Features: The accused feature is the use of Defendants' proposed generic ferric citrate tablet as instructed by its labeling (Compl. ¶¶123, 125).

  • Multi-Patent Capsule: U.S. Patent No. 9,328,133, entitled "Ferric Organic Compounds, Uses Thereof and Methods of Making Same," issued May 3, 2016.

    • Technology Synopsis: This patent claims methods of treating hyperphosphatemia and metabolic acidosis by administering pharmaceutical compositions of the novel ferric citrate. The claims cover therapeutic methods using compositions that possess the key high surface area characteristic.
    • Asserted Claims: Claims 1, 8, 10, and 17 (Compl. ¶131).
    • Accused Features: The accused feature is the use of Defendants' proposed generic ferric citrate tablet as instructed by its labeling (Compl. ¶¶131, 134).

  • Multi-Patent Capsule: U.S. Patent No. 9,757,416, entitled "Pharmaceutical-Grade Ferric Organic Compounds, Uses Thereof and Methods of Making Same," issued September 12, 2017.

    • Technology Synopsis: This patent claims methods of treating hyperphosphatemia or metabolic acidosis in a subject with chronic kidney disease by administering tablets containing the novel ferric citrate. The claims are directed to therapeutic use in a specific patient population.
    • Asserted Claims: Claims 1 and 23 (Compl. ¶140).
    • Accused Features: The accused feature is the use of Defendants' proposed generic ferric citrate tablet as instructed by its labeling (Compl. ¶¶140, 142).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is "Watson's Proposed Product," a generic version of AURYXIA® (Ferric Citrate) tablets, which is the subject of ANDA No. 208244 submitted to the FDA (Compl. ¶1).

Functionality and Market Context

  • The proposed generic product is an oral, iron-based medicine containing ferric citrate as the active pharmaceutical ingredient (Compl. ¶26). Its intended use, as specified in the ANDA filing, is 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. ¶26). As a generic drug, it is intended to be a lower-cost, bioequivalent substitute for the branded AURYXIA® product upon receiving FDA approval (Compl. ¶1, ¶50).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for a claim-chart analysis. The infringement allegations are pleaded generally for each patent, stating that the submission of ANDA No. 208244 for a product that will be manufactured, used, or sold before patent expiration constitutes infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶¶55, 62). The core theory is that by seeking approval to market a generic version of AURYXIA®, Defendants necessarily intend to market a product that has the same chemical composition, physical properties, and labeled indications for use as the branded drug, which Plaintiffs allege are covered by the patents-in-suit.

  • Identified Points of Contention:
    • Physical Properties Mismatch: For product claims, such as claim 1 of the ’851 Patent, a central technical question will be whether Defendants' proposed generic ferric citrate product actually possesses the claimed "intrinsic dissolution rate between 1.9 and 4.0 mg/cm²/min." The dispute may center on the results of laboratory testing of Defendants' ANDA samples and the specific methodology used for such tests.
    • Scope of Method Claims: For method of treatment claims, such as claim 7 of the ’423 Patent, the dispute may focus on whether Defendants' proposed product label will induce infringement. This raises the question of whether the instructions for use on the label direct physicians and patients to "administer... an effective amount" of the drug for the specific purpose of "reducing serum levels of phosphate" in a manner that falls within the scope of the claims.

V. Key Claim Terms for Construction

  • The Term: "intrinsic dissolution rate between 1.9 and 4.0 mg/cm²/min" (from ’851 Patent, claim 1; ’423 Patent, claim 7).
    • Context and Importance: This quantitative property is the primary feature asserted to distinguish the patented form of ferric citrate from prior art forms. The outcome of the infringement analysis for numerous patents in the portfolio may depend entirely on whether Defendants' product is measured to have a dissolution rate that falls within this claimed range.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claims provide a clear numerical range. The specification of the ’851 Patent provides multiple examples of novel ferric citrate batches with dissolution rates falling squarely within this range, such as 3.08, 3.82, and 4.00 mg/cm²/min, suggesting the range is well-supported and intended to cover these embodiments. (’851 Patent, col. 10:Table 3).
      • Evidence for a Narrower Interpretation: The claim specifies the rate is "as determined by the USP intrinsic dissolution assay in water." A party may argue that the precise parameters and experimental conditions detailed in the patent's examples for conducting this assay are definitional and essential to interpreting the claim scope, potentially narrowing the range of accused products that would be found to meet this limitation. (’851 Patent, col. 10:36-67).
  • The Term: "an effective amount" (from ’423 Patent, claim 7).
    • Context and Importance: In this method of treatment claim, the definition of an "effective amount" is critical for determining the scope of infringing activity. Practitioners may focus on this term because its construction will define the dosage levels that constitute infringement.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification of the related ’851 patent suggests a therapeutic dose for hyperphosphatemia is between 3 to 6 grams/day, providing a potential objective range for what is "effective." (’851 Patent, col. 3:15-17).
      • Evidence for a Narrower Interpretation: A party could argue that "effective" must be tied to a clinically meaningful reduction in serum phosphate levels as demonstrated in the patent. The specification of the ’423 patent incorporates clinical data showing dose-dependent efficacy, which could be used to argue that only certain dosages that achieve a statistically significant phosphate reduction, as shown in that data, are "effective" under the claim. (’423 Patent, Figs. 9-10).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement of infringement for the asserted method-of-use patents, stating that upon FDA approval, Defendants will encourage healthcare providers and patients to use the proposed generic product in an infringing manner through its product labeling and instructions (Compl. ¶¶64, 80, 109). Contributory infringement is also alleged on the basis that the product is especially made for an infringing use and is not a staple article of commerce with substantial non-infringing uses (Compl. ¶¶65, 81, 110).
  • Willful Infringement: The complaint does not use the term "willful." However, for each patent, it alleges that the case is "an exceptional one" and requests an award of attorneys' fees pursuant to 35 U.S.C. § 285 (Compl. ¶¶60, 68, 75). These allegations are based on the totality of Defendants' conduct, including the filing of the ANDA.

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

  • A core issue will be one of empirical measurement: Does the Defendants' proposed generic ferric citrate, when tested under the conditions specified or implied by the patents, exhibit the claimed "intrinsic dissolution rate"? This central factual dispute will likely be resolved through competing expert testing and analysis of the ANDA product samples.
  • A key legal and factual question will be one of induced infringement: Assuming the method-of-use claims are valid, will the contents of Defendants' proposed product label, which must largely mirror the label of the branded drug, be sufficient to establish that Defendants actively encouraged and intended for physicians and patients to perform the patented methods of treatment?
  • A foundational issue for the entire case will be the validity of the claims: Although not detailed in the complaint, the Defendants' Paragraph IV certification asserts invalidity. The case may therefore turn on whether the claimed dissolution rates and surface areas represent a non-obvious advance over prior art forms of ferric citrate known at the time of the invention.