DCT

1:23-cv-00331

Keryx Biopharma Inc v. Zydus Worldwide DMCC

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00331, D. Del., 03/24/2023
  • Venue Allegations: Plaintiffs allege venue is proper because Defendant Zydus Pharmaceuticals (USA) Inc. is subject to personal jurisdiction in the District of Delaware and has committed acts of infringement there. Venue is alleged to be proper for the foreign defendants because they are foreign corporations.
  • Core Dispute: Plaintiffs allege that Defendants’ 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 fourteen U.S. patents.
  • Technical Context: The technology concerns ferric citrate compounds and pharmaceutical dosage forms for treating hyperphosphatemia (elevated serum phosphorus) and iron deficiency anemia, conditions commonly associated with chronic kidney disease.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendants' submission of ANDA No. 218192 with a Paragraph IV certification alleging that the patents-in-suit are invalid, unenforceable, or will not be infringed. Plaintiffs received notice of this certification no earlier than February 10, 2023. The complaint notes previous litigation involving Defendants in the District of Delaware to support arguments for personal jurisdiction and venue.

Case Timeline

Date Event
2003-02-19 Earliest Priority Date for ’851, ’423, ’298, ’642, ’896, ’257, ’258, ’976, ’349, ’316, ’133, ’416 Patents
2009-07-21 Earliest Priority Date for ’191 and ’039 Patents
2010-08-03 ’851 Patent Issued
2012-01-10 ’423 Patent Issued
2012-10-30 ’298 Patent Issued
2012-12-25 ’642 Patent Issued
2013-12-17 ’896 Patent Issued
2014-06-17 ’257 Patent Issued
2014-06-17 ’258 Patent Issued
2014-09-30 ’976 Patent Issued
2014-12-02 ’349 Patent Issued
2015-06-09 ’316 Patent Issued
2016-05-03 ’133 Patent Issued
2016-07-12 ’191 Patent Issued
2017-09-12 ’416 Patent Issued
2019-05-28 ’039 Patent Issued
2023-02-10 Plaintiffs received Defendants’ Paragraph IV Notice Letter (earliest date)
2023-03-24 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"

  • Issued: August 3, 2010

The Invention Explained

  • Problem Addressed: The patent describes the problem that commercially available forms of ferric citrate have slow dissolution rates, requiring patients with renal failure to take substantially large oral doses (e.g., 1 gram) to effectively treat hyperphosphatemia ('851 Patent, col. 1:46-61).
  • The Patented Solution: The invention is a novel solid form of ferric citrate characterized by an enhanced dissolution rate, which is attributed to its large active surface area ('851 Patent, col. 2:8-14, 4:5-10). The specification describes a specific synthesis method involving the formation of a uniform polyiron oxo colloidal suspension and subsequent precipitation with an organic solvent to produce this amorphous, more soluble form of ferric citrate ('851 Patent, col. 7:1-41; Fig. 1).
  • Technical Importance: This more soluble form of ferric citrate allows for more effective oral delivery, potentially enabling lower doses to treat hyperphosphatemia and metabolic acidosis in patients with kidney disease ('851 Patent, col. 2:19-22).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶51).
  • Claim 1 of the ’851 Patent recites:
    • 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 of ferric citrate is synthesized by a method comprising several steps including forming a ferric-citric acid solution and precipitating with an organic solvent.
  • The complaint alleges infringement of "one or more of the claims," which may suggest a future intent to assert dependent claims (Compl. ¶51).

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 addresses the need for a scalable manufacturing process that can consistently produce pharmaceutical-grade ferric citrate that complies with established Manufacture Release Specifications ('423 Patent, col. 2:1-4). This implies that prior methods lacked the necessary quality control for large-scale production suitable for pharmaceuticals.
  • The Patented Solution: The invention provides a detailed manufacturing and quality control process for producing pharmaceutical-grade ferric citrate with desirable solubility and purity ('423 Patent, col. 2:15-25). The process includes specific quality control checkpoints, such as testing the pH of the ferric hydroxide slurry and measuring the percentage of chloride in the precipitate, to ensure the final product meets release specifications ('423 Patent, Fig. 1).
  • Technical Importance: This invention provides a reliable method for large-scale production of a consistent, pharmaceutical-grade ferric citrate, enabling its use as an active pharmaceutical ingredient in regulated drug products ('423 Patent, col. 2:20-25).

Key Claims at a Glance

  • The complaint asserts independent claim 7 (Compl. ¶61).
  • Claim 7 of the ’423 Patent recites:
    • A method of treating hyperphosphatemia in a subject,
    • comprising administering to said subject an effective amount of a pharmaceutical-grade ferric organic compound,
    • wherein said pharmaceutical-grade ferric organic compound is prepared from a form of ferric citrate having an intrinsic dissolution rate of at least 1.88 mg/cm²/min.
  • The complaint’s allegation of infringement of "one or more of the claims" suggests a possible intent to assert dependent claims later in the litigation (Compl. ¶61).

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 is directed to a pharmaceutical composition containing a form of ferric citrate with a high BET active surface area (at least 16 sq. m/g), which contributes to its enhanced solubility and therapeutic effect ('298 Patent, Abstract; col. 4:3-11). The problem solved is providing a more effective oral therapy for disorders like hyperphosphatemia by using a more soluble active ingredient.
  • Asserted Claims: Claim 1 (Compl. ¶69).
  • Accused Features: The Zydus Proposed Product is accused of being or containing the claimed pharmaceutical composition (Compl. ¶69).

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 an intrinsic dissolution rate between 1.88-4.0 mg/cm²/min ('642 Patent, col. 12:5-10). This specific dissolution profile distinguishes it from prior art forms of ferric citrate, addressing the problem of poor solubility that required patients to take large doses.
  • Asserted Claims: Claims 1, 8, 10, and 17 (Compl. ¶79).
  • Accused Features: The Zydus Proposed Product is accused of being or containing the claimed form of ferric citrate, and its administration is alleged to infringe the asserted method claims (Compl. ¶79, ¶82).

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 a method of treating hyperphosphatemia by administering an orally administrable form of ferric citrate that is prepared from a form of ferric citrate having a high intrinsic dissolution rate ('896 Patent, col. 12:15-22). The invention addresses the need for effective oral treatments for hyperphosphatemia.
  • Asserted Claims: Claim 1 (Compl. ¶88).
  • Accused Features: The use of the Zydus Proposed Product as directed by its proposed labeling is alleged to infringe this method of treatment (Compl. ¶88, ¶91).

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 method of treating hyperphosphatemia by administering a pharmaceutical-grade ferric citrate that has a BET active surface area greater than 16 sq. m/g ('257 Patent, col. 12:17-23). The higher surface area leads to better dissolution and thus more effective treatment.
  • Asserted Claims: Claim 1 (Compl. ¶98).
  • Accused Features: The use of the Zydus Proposed Product as directed by its proposed labeling is alleged to infringe this method of treatment (Compl. ¶98, ¶101).

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 an orally administrable form of ferric citrate prepared from a form having an intrinsic dissolution rate of at least 1.88 mg/cm²/min ('258 Patent, col. 12:1-7). The invention focuses on the improved properties of the final dosage form derived from the novel ferric citrate.
  • Asserted Claims: Claim 1 (Compl. ¶108).
  • Accused Features: The Zydus Proposed Product is accused of being the claimed orally administrable form of ferric citrate (Compl. ¶108).

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 is directed to a method of treating hyperphosphatemia by administering an orally administrable form of ferric citrate prepared from a form having an intrinsic dissolution rate of at least 1.88 mg/cm²/min ('976 Patent, claim 1). It solves the problem of providing an effective oral therapy for managing high phosphate levels.
  • Asserted Claims: Claim 1 (Compl. ¶118).
  • Accused Features: The intended use of the Zydus Proposed Product, as instructed by its labeling, is alleged to infringe the claimed method (Compl. ¶118, ¶120).

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 tablet form of ferric citrate prepared from a form having an intrinsic dissolution rate of at least 1.88 mg/cm²/min ('349 Patent, claim 1). The invention focuses on a specific dosage form for the improved ferric citrate.
  • Asserted Claims: Claim 1 (Compl. ¶127).
  • Accused Features: The intended use of the Zydus Proposed Product in its tablet form is alleged to infringe this method of treatment (Compl. ¶127, ¶129).

U.S. Patent No. 9,050,316 - "Pharmaceutical-Grade Ferric Organic Compounds, Uses Thereof and Method of Making Same"

  • Issued: June 9, 2015
  • Technology Synopsis: This patent claims a method of treating hyperphosphatemia by administering tablets comprising ferric citrate having a BET active surface area of at least 16 m²/g ('316 Patent, claim 1). The high surface area enhances bioavailability and efficacy.
  • Asserted Claims: Claim 1 (Compl. ¶136).
  • Accused Features: The intended use of the Zydus Proposed Product tablets is alleged to infringe this method of treatment (Compl. ¶136, ¶139).

U.S. Patent No. 9,387,191 - "Ferric Citrate Dosage Forms"

  • Issued: July 12, 2016
  • Technology Synopsis: This patent is directed to a specific ferric citrate tablet formulation with defined amounts of pregelatinized starch as a binder and a lubricant, resulting in a tablet with specific physical properties such as friability and dissolution rate ('191 Patent, Abstract; claim 1). The invention solves the problem of creating a stable, effective, and manufacturable tablet using the active ferric citrate ingredient.
  • Asserted Claims: Claims 1, 6, 11, and 16 (Compl. ¶146).
  • Accused Features: The Zydus Proposed Product tablet formulation is accused of infringing the claimed composition and its use is accused of infringing the claimed methods (Compl. ¶146, ¶149).

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 a ferric citrate compound with a specific intrinsic dissolution rate (1.88-4.0 mg/cm²/min) and its use in treating hyperphosphatemia ('133 Patent, claims 1, 8). It addresses the need for a more soluble and therefore more effective form of ferric citrate.
  • Asserted Claims: Claims 1, 8, 10, and 17 (Compl. ¶156).
  • Accused Features: The Zydus Proposed Product is accused of being or containing the claimed ferric citrate, and its administration is alleged to infringe the asserted method claims (Compl. ¶156, ¶159).

U.S. Patent No. 9,757,416 - "Pharmaceutical-Grade Ferric Organic Compounds, Uses Thereof and Method of Making Same"

  • Issued: September 12, 2017
  • Technology Synopsis: This patent claims a method of treating hyperphosphatemia by administering a tablet containing ferric citrate with a high BET active surface area ('416 Patent, claims 1, 23). The invention focuses on the therapeutic benefit derived from the specific physical properties of the active ingredient in the tablet form.
  • Asserted Claims: Claims 1 and 23 (Compl. ¶166).
  • Accused Features: The use of the Zydus Proposed Product tablets as instructed by its proposed labeling is alleged to infringe the claimed methods (Compl. ¶166, ¶168).

U.S. Patent No. 10,300,039 - "Ferric Citrate Dosage Forms"

  • Issued: May 28, 2019
  • Technology Synopsis: This patent claims a method for treating hyperphosphatemia by administering a specific tablet formulation of ferric citrate that includes pregelatinized starch and a lubricant, and which exhibits certain physical properties like a friability of less than 1% and a specific dissolution profile ('039 Patent, claim 1). The invention addresses the challenge of creating a robust and effective oral dosage form for ferric citrate.
  • Asserted Claims: Claims 1, 4, 5, 8, 11, 14, and 15 (Compl. ¶175).
  • Accused Features: The use of the Zydus Proposed Product tablets as directed by its proposed labeling is alleged to infringe the claimed methods (Compl. ¶175, ¶177).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is "Zydus's Proposed Product," which is a generic version of Keryx's AURYXIA® (Ferric Citrate) Tablets for which Defendants seek FDA approval via ANDA No. 218192 (Compl. ¶1).
  • Functionality and Market Context: The complaint alleges that the Zydus Proposed Product is an orally available, iron-based medicine intended 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. ¶27). As a generic drug submitted through an ANDA, it is intended to be a therapeutic equivalent to the branded AURYXIA® product. The complaint alleges that upon FDA approval, Defendants will manufacture, use, sell, offer to sell, or import the product in the United States (Compl. ¶44). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain or reference a claim chart exhibit providing a detailed element-by-element infringement analysis. This is common in ANDA litigation initiated before the ANDA itself is produced to the plaintiff. The complaint alleges infringement based on the act of submitting the ANDA, which seeks approval for a product that, if marketed, would allegedly infringe the patents-in-suit (Compl. ¶¶51, 61). The infringement theory is that the Zydus Proposed Product will have the same active ingredient, dosage form, and indications as AURYXIA®, and therefore will meet the limitations of the asserted composition, formulation, and method-of-use claims.

  • Identified Points of Contention:
    • Physical Properties: For composition claims like claim 1 of the ’851 Patent, a central question will be whether Zydus's proposed ferric citrate product possesses the specific physical properties required by the claims, such as the claimed "intrinsic dissolution rate" and BET active surface area. This suggests a potential dispute centered on analytical testing and expert interpretation of the results.
    • Method of Treatment: For method claims like claim 7 of the ’423 Patent, the analysis raises the question of whether the proposed labeling for the Zydus product will instruct or encourage medical professionals and patients to administer the drug in a manner that directly infringes the claimed method of treating hyperphosphatemia. The scope of the term "effective amount" may also become a point of contention.

V. Key Claim Terms for Construction

  • The Term: "intrinsic dissolution rate" (appearing in claim 1 of the ’851 Patent and claim 7 of the ’423 Patent)

  • Context and Importance: This term is a quantitative physical property used to define the novel form of ferric citrate and is central to the infringement and validity analysis for numerous asserted patents. Practitioners may focus on this term because the dispute will likely involve competing expert analyses of whether the accused product's dissolution rate falls within the claimed numerical range.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patents state the rate is "as determined by USP (United States Pharmacopeia) intrinsic dissolution assay in water" ('851 Patent, col. 12:3-5), which could suggest that any standard application of that test method is appropriate.
    • Evidence for a Narrower Interpretation: The specifications provide specific examples and dissolution profiles under particular conditions (e.g., pH 8.0), and show tables comparing the novel form to commercially available forms ('851 Patent, Table 3; col. 10:43-67). Defendants may argue that the term should be construed in light of these specific examples and testing conditions disclosed in the patent.

  • The Term: "pharmaceutical-grade" (appearing in claim 7 of the ’423 Patent)

  • Context and Importance: This term qualifies the claimed ferric organic compound. Its definition is critical because it may import specific purity and consistency requirements into the claim, distinguishing it from less-refined chemical-grade compounds.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The term could be interpreted broadly to mean any ferric citrate compound suitable for use in a pharmaceutical product, consistent with general industry understanding.
    • Evidence for a Narrower Interpretation: The specification of the '423 Patent is focused on a specific manufacturing and quality control process designed to "consistently produce ferric organic compounds...of the required pharmaceutical grade" ('423 Patent, col. 2:1-4). This may support an argument that "pharmaceutical-grade" should be limited to compounds made with a level of quality control and consistency taught in the patent.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement for all asserted patents, based on the allegation that Defendants' proposed product labeling will instruct and encourage healthcare providers and patients to use the product in an infringing manner (Compl. ¶¶54, 63). The complaint also pleads contributory infringement, alleging the Zydus product is a material part of the claimed inventions, is especially made or adapted for infringing use, and is not a staple article of commerce (Compl. ¶¶55, 64).
  • Willful Infringement: The complaint does not explicitly allege willful infringement. However, for each patent, it states that the case is "an exceptional one" and seeks an award of reasonable attorneys' fees under 35 U.S.C. § 285 (Compl. ¶¶59, 67). This allegation is based on the totality of circumstances surrounding the infringement, which the plaintiffs will need to establish during litigation.

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

  • A core issue will be one of product characterization: Can Plaintiffs demonstrate through chemical and physical testing that the Zydus Proposed Product will necessarily meet the specific quantitative limitations of the composition claims, such as the "intrinsic dissolution rate" and "BET active surface area" that define the patented form of ferric citrate? This will likely involve a significant battle of competing expert evidence.
  • A key legal question will be induced infringement: For the numerous asserted method-of-treatment claims, the case will turn on whether the proposed label for the Zydus product instructs users to administer the drug for the claimed indications (e.g., hyperphosphatemia) in a manner that would lead to direct infringement by patients and doctors.
  • A central dispute for the formulation patents will be one of compositional identity: Does the combination of active ingredient and excipients in Zydus's proposed tablet fall within the specific component and weight percentage ranges required by claims in patents such as the ’191 and ’039 patents, and does the final tablet exhibit the claimed physical properties like friability and disintegration time?