DCT

1:18-cv-02012

Keryx Biopharma Inc v. Teva Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-02012, D. Del., 04/10/2019
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Teva Pharmaceuticals USA, Inc. is incorporated in the state of Delaware.
  • Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiffs’ AURYXIA® (ferric citrate) tablets constitutes an act of infringement of twelve U.S. patents.
  • Technical Context: The technology concerns novel forms of ferric citrate, a compound used as a phosphate binder to control high serum phosphorus levels (hyperphosphatemia) in adult patients with chronic kidney disease.
  • Key Procedural History: This is a Hatch-Waxman action initiated after Defendant sent a Paragraph IV notice letter, no earlier than November 5, 2018, asserting that the patents-in-suit are invalid, unenforceable, and/or will not be infringed by its proposed generic product. The complaint was filed within the 45-day statutory window, triggering a 30-month stay of FDA approval for the Defendant's ANDA.

Case Timeline

Date Event
2003-02-19 Priority Date for ’851, ’642, ’896, ’257, ’258, ’976, ’349, ’133 Patents
2003-04-15 Priority Date for ’423, ’298 Patents
2004-02-18 Priority Date for ’316, ’416 Patents
2010-08-03 U.S. Patent 7,767,851 Issues
2012-01-10 U.S. Patent 8,093,423 Issues
2012-10-30 U.S. Patent 8,299,298 Issues
2012-12-25 U.S. Patent 8,338,642 Issues
2013-12-17 U.S. Patent 8,609,896 Issues
2014-06-17 U.S. Patent 8,754,257 Issues
2014-06-17 U.S. Patent 8,754,258 Issues
2014-09-30 U.S. Patent 8,846,976 Issues
2014-12-02 U.S. Patent 8,901,349 Issues
2015-06-09 U.S. Patent 9,050,316 Issues
2016-05-03 U.S. Patent 9,328,133 Issues
2017-09-12 U.S. Patent 9,757,416 Issues
2018-11-05 Defendant sends Paragraph IV Certification Notice Letter to Plaintiffs
2019-04-10 First Amended Complaint Filed

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

  • Patent Identification: U.S. Patent No. 7,767,851, “Ferric Organic Compounds, Uses Thereof and Methods of Making Same,” issued August 3, 2010.

  • The Invention Explained:

    • Problem Addressed: The patent’s background section states that existing crystalline forms of ferric citrate, used to treat hyperphosphatemia, dissolve slowly, requiring patients to take substantially large oral doses (’851 Patent, col. 1:47-62).
    • The Patented Solution: The invention is a novel solid form of ferric citrate with an enhanced dissolution rate, which is achieved through a specific synthesis method. This method involves creating a uniform polyiron oxo colloidal suspension, isolating a precipitate, and reacting it with crystalline citric acid before precipitating the final compound with an organic solvent (’851 Patent, col. 2:22-42; Fig. 1). This process results in a product with a large active surface area, intended to make the compound more effective for oral delivery (’851 Patent, col. 2:59-62).
    • Technical Importance: A more soluble form of ferric citrate could allow for more effective oral phosphate binding, potentially enabling lower doses and reducing the pill burden for patients with chronic kidney disease.

  • Key Claims at a Glance:

    • The complaint asserts at least independent claim 1 (Compl. ¶37).
    • The essential elements of independent claim 1 are:
      • A solid form of ferric citrate;
      • Having a formula of C6H5O7Fe;
      • Having an intrinsic dissolution rate between 1.9 and 4.0 mg/cm²/min, as determined by the USP intrinsic dissolution assay in water; and
      • Being synthesized by a five-step method involving (a) adding an alkaline metal hydroxide to a ferric chloride solution, (b) isolating a ferric hydroxide precipitate, (c) forming a suspension of the precipitate, (d) adding citric acid and heating, and (e) precipitating the final product with an organic solvent.
    • The complaint does not explicitly reserve the right to assert dependent claims for this patent.

  • Patent Identification: 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 background identifies a need for a scalable and consistent manufacturing process for pharmaceutical-grade ferric citrate that complies with established standards, which was not previously disclosed for the more soluble forms of the compound (’423 Patent, col. 1:64–col. 2:2).
    • The Patented Solution: The invention provides a detailed, multi-step manufacturing and quality control process to consistently produce pharmaceutical-grade ferric citrate. The method includes specific in-process quality control checks, such as maintaining the pH above 7.0 during precipitation and ensuring the chloride content of an intermediate precipitate is below 5%, to ensure the final product meets pharmaceutical release specifications (’423 Patent, Fig. 1; col. 2:17-31).
    • Technical Importance: This invention provides a reliable and scalable process critical for the commercial manufacturing of a consistent, high-purity active pharmaceutical ingredient suitable for human use.

  • Key Claims at a Glance:

    • The complaint asserts at least claims 1-7, of which claim 1 is independent (Compl. ¶44).
    • The essential elements of independent claim 1 are a multi-step method of preparing pharmaceutical-grade ferric citrate, including the steps of:
      • (a-c) mixing ferric chloride hexahydrate and NaOH solutions to form a Fe(OH)3 precipitate;
      • (d) maintaining the pH of the solution above 7.0;
      • (e-g) isolating, washing, and re-suspending the precipitate;
      • (h-i) adding citric acid and heating the solution to 90-100° C. for 30 to 120 minutes;
      • (j-l) adding more citric acid, cooling, and maintaining pH between 0.8-1.5; and
      • (m-q) filtering, precipitating with acetone, isolating, washing, and drying the final ferric citrate product.
    • The complaint explicitly asserts dependent claims 2-7.

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

    • Technology Synopsis: This patent claims a pharmaceutical-grade ferric citrate composition defined by specific physical properties, including a BET active surface area of at least 16 sq. m/g. It also covers methods of making and using this composition to treat disorders like hyperphosphatemia (’298 Patent, Abstract; col. 1:50-59).
    • Asserted Claims: At least claim 1 (Compl. ¶52).
    • Accused Features: Teva’s Proposed Product is alleged to be, or be made by a process that results in, the claimed pharmaceutical-grade ferric citrate composition (Compl. ¶52, ¶54).

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

    • Technology Synopsis: This patent claims a specific form of ferric citrate characterized by a BET active surface area greater than 16 sq. m/g. It further claims methods of treating hyperphosphatemia and metabolic acidosis by administering this form of ferric citrate (’642 Patent, Abstract; col. 12:1-17).
    • Asserted Claims: At least claims 1, 8-10, and 17-18 (Compl. ¶59).
    • Accused Features: Teva’s Proposed Product is alleged to be the claimed form of ferric citrate, and its intended use is alleged to infringe the claimed methods of treatment (Compl. ¶59, ¶61-63).

  • Multi-Patent Capsule: U.S. Patent No. 8,609,896, “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 defined by an intrinsic dissolution rate of at least 1.88 mg/cm²/min. The claims also cover methods of treating hyperphosphatemia by administering this specific form of the compound (’896 Patent, col. 12:4-21).
    • Asserted Claims: At least claim 1 (Compl. ¶68).
    • Accused Features: Teva’s Proposed Product is alleged to be the claimed form of ferric citrate, and its intended use is alleged to infringe the claimed methods of treatment (Compl. ¶68, ¶70).

  • Multi-Patent Capsule: U.S. Patent No. 8,754,257, “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 an intrinsic dissolution rate of 1.88-4.0 mg/cm²/min. The claims specify dosage amounts and forms, such as a 500 mg capsule, for reducing serum phosphate levels (’257 Patent, col. 26:10-22).
    • Asserted Claims: At least claim 1 (Compl. ¶75).
    • Accused Features: Teva's Proposed Product is alleged to be the claimed pharmaceutical composition (Compl. ¶75, ¶77).

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

    • Technology Synopsis: This patent claims a form of ferric citrate defined by a specific method of synthesis and having an intrinsic dissolution rate of 1.9 to 4.0 mg/cm²/min. It is a product-by-process patent similar in scope to the ’851 patent (’258 Patent, col. 12:1-24).
    • Asserted Claims: At least claim 1 (Compl. ¶82).
    • Accused Features: Teva’s Proposed Product is alleged to be the claimed form of ferric citrate (Compl. ¶82, ¶84).

  • Multi-Patent Capsule: U.S. Patent No. 8,846,976, “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 an orally administrable form of ferric citrate that is prepared from a form having an intrinsic dissolution rate of at least 1.88 mg/cm²/min. The claims cover various dosage forms, including tablets (’976 Patent, col. 12:15-31).
    • Asserted Claims: At least claim 1 (Compl. ¶89).
    • Accused Features: The intended use of Teva’s Proposed Product is alleged to infringe the claimed method of treatment (Compl. ¶89, ¶91-92).

  • Multi-Patent Capsule: U.S. Patent No. 8,901,349, “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 an orally administrable form of ferric citrate with a BET active surface area greater than about 16 m²/g. The claims specify dosage ranges and forms (’349 Patent, col. 12:15-31).
    • Asserted Claims: At least claim 1 (Compl. ¶97).
    • Accused Features: The intended use of Teva’s Proposed Product is alleged to infringe the claimed method of treatment (Compl. ¶97, ¶99-100).

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

    • Technology Synopsis: This patent claims methods of treating hyperphosphatemia by administering tablets containing ferric citrate, where the tablets are prepared from a form of ferric citrate having a BET active surface area of at least 16 m²/g. The claims cover specific patient populations, such as those with chronic kidney disease (’316 Patent, col. 25:25-41).
    • Asserted Claims: At least claims 1 and 12 (Compl. ¶105).
    • Accused Features: The intended use of Teva’s Proposed Product is alleged to infringe the claimed methods of treatment (Compl. ¶105, ¶107-108).

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

    • Technology Synopsis: This patent claims an orally administrable form of ferric citrate prepared from a form of ferric citrate having a specified intrinsic dissolution rate. The claims are directed to the composition itself, including specific dosage forms like a tablet (’133 Patent, col. 12:1-24).
    • Asserted Claims: At least claims 1, 8-10, and 17-18 (Compl. ¶113).
    • Accused Features: Teva’s Proposed Product is alleged to be the claimed composition, and its intended use is alleged to infringe the claimed methods (Compl. ¶113, ¶115-117).

  • Multi-Patent Capsule: U.S. Patent No. 9,757,416, “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 and metabolic acidosis by administering tablets comprising ferric citrate prepared from a form having a BET active surface area of at least 16 m²/g. The claims specify dosage amounts and patient populations (’416 Patent, col. 26:1-36).
    • Asserted Claims: At least claims 1, 12, 23, and 30 (Compl. ¶122).
    • Accused Features: The intended use of Teva’s Proposed Product is alleged to infringe the claimed methods of treatment (Compl. ¶122, ¶124-125).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is "Teva's Proposed Product," a generic version of AURYXIA® (Ferric Citrate) Tablets, as described in Teva's Abbreviated New Drug Application (ANDA) No. 212563 submitted to the FDA (Compl. ¶1).
  • Functionality and Market Context:
    • The complaint alleges that Teva’s Proposed Product is a generic version of Keryx’s AURYXIA®, an orally available, iron-based medicine (Compl. ¶1, ¶20). The intended use of the product is for the control of serum phosphorus levels in adult patients with chronic kidney disease (CKD) on dialysis, and for the treatment of iron deficiency anemia in adult patients with CKD not on dialysis (Compl. ¶20).
    • The complaint alleges that upon receiving FDA approval, Teva intends to commercially manufacture, import, market, offer for sale, and/or sell its Proposed Product in the United States prior to the expiration of the patents-in-suit (Compl. ¶1, ¶23).
    • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed infringement analysis or claim chart for any of the asserted patents. The infringement allegations are statutory, based on Defendant's submission of ANDA No. 212563, which Plaintiffs contend is an act of infringement under 35 U.S.C. § 271(e)(2)(A) because it seeks approval to market a generic drug for uses claimed in the patents-in-suit before their expiration (Compl. ¶37, ¶44).

  • Identified Points of Contention:
    • ’851 Patent: Claim 1 is a product-by-process claim, reciting both a product with specific properties ("intrinsic dissolution rate") and the method for making it. A central question for infringement will be whether Teva's proposed generic product meets the claimed properties. If Teva uses a different process, a further question may arise as to whether the product itself is structurally identical to the product made by the claimed process, which could still support a finding of infringement.
    • ’423 Patent: Claim 1 is a method-of-manufacture claim. The primary question will be whether the manufacturing process described in Teva's confidential ANDA includes every step recited in the claim. The analysis will likely depend entirely on a comparison of Teva's confidential process documentation with the claim language.

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)

  • Context and Importance: This term is a critical quantitative limitation defining the patented product in the ’851 Patent and related patents. The dispute may turn on whether Teva's product exhibits a dissolution rate within this range when measured by the specified USP assay. Practitioners may focus on this term because it is a measurable physical property that distinguishes the claimed invention from prior art ferric citrate.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The claim language itself defines the scope by referencing a standardized test: "as determined by the USP intrinsic dissolution assay in water" (’851 Patent, col. 12:3-5). This may suggest that any product falling within the range, regardless of other minor physical differences, infringes.
    • Evidence for a Narrower Interpretation: The specification provides specific examples of novel ferric citrate batches with measured dissolution rates of 3.82, 4.00, 2.68, and 2.95 mg/cm²/min (’851 Patent, Table 3). A party could argue that these examples define the core of the invention and that products with characteristics substantially different from these embodiments, even if technically within the claimed numerical range, do not infringe.

  • The Term: "pharmaceutical-grade ferric citrate" (from ’423 Patent, claim 1)

  • Context and Importance: The entire ’423 Patent is directed to a process for making a "pharmaceutical-grade" product. The definition of this term will be central to determining whether Teva's manufacturing process, which must also produce a pharmaceutical-grade product, infringes the claimed method.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: A party might argue this term simply means ferric citrate that is suitable for use in a human pharmaceutical product, consistent with general industry and regulatory standards.
    • Evidence for a Narrower Interpretation: The patent specification provides extensive detail on the specific quality control measures and release specifications required for the final product to be considered "pharmaceutical-grade" in the context of the invention. This includes limits on impurities like chloride and specific outcomes for identity tests (’423 Patent, Fig. 1; Table A). A party could argue that the term should be narrowly construed to mean ferric citrate meeting these specific, disclosed criteria.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced and contributory infringement for patents with method-of-use claims (e.g., the ’423, ’642, ’976, and other patents). The basis for these allegations is that Teva, by filing an ANDA for the patented indications, knows its product is designed for an infringing use and will intentionally encourage direct infringement by physicians and patients upon FDA approval (Compl. ¶46, ¶47, ¶62, ¶63).
  • Willful Infringement: The complaint does not explicitly use the word "willful." However, it repeatedly alleges that each count represents an "exceptional case" and requests an award of attorneys' fees under 35 U.S.C. § 285, a remedy often associated with findings of willful infringement or other litigation misconduct (Compl. ¶42, ¶50, ¶57).

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

  • A central issue will be one of process comparison: does the manufacturing process for Teva's generic ferric citrate, as detailed in its confidential ANDA, practice the specific multi-step methods claimed in patents such as the ’423 Patent? Access to Teva's ANDA will be the determining factor for this question.
  • A key evidentiary question will be one of property matching: does Teva’s proposed final drug product possess the specific physical properties, such as the "intrinsic dissolution rate" claimed in the ’851 Patent and the "BET active surface area" claimed in the ’298 Patent? This will likely be a battle of technical experts interpreting analytical data from both parties' products.
  • A foundational question, raised by Teva's Paragraph IV certification, will be one of validity: are the claimed forms of ferric citrate, characterized by specific physical properties and manufacturing processes, novel and non-obvious over previously known forms of ferric citrate and conventional pharmaceutical manufacturing techniques?