DCT

1:19-cv-00220

Keryx Biopharma Inc v. Chemo Research SL

Log In
Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-00220, D. Del., 02/01/2019
  • Venue Allegations: Venue is alleged to be proper as Defendants are foreign corporations. Personal jurisdiction is alleged based on Defendants' systematic and continuous contacts with the State of Delaware and the United States as a whole, including activities related to preparing and submitting Abbreviated New Drug Applications (ANDAs) to the FDA.
  • Core Dispute: Plaintiffs allege that Defendants' filing of an ANDA to market a generic version of Plaintiffs' AURYXIA® (Ferric Citrate) tablets constitutes an act of patent infringement.
  • Technical Context: The patents relate to ferric citrate compounds, pharmaceutical formulations, and methods for treating renal failure, specifically for controlling serum phosphorus levels in patients with chronic kidney disease.
  • Key Procedural History: The litigation was initiated under the Hatch-Waxman Act, triggered by Defendants' submission of ANDA No. 212738 to the FDA. The ANDA included a Paragraph IV Certification alleging that the patents-in-suit are invalid, unenforceable, or will not be infringed by the proposed generic product.

Case Timeline

Date Event
1996-12-16 U.S. Patent No. 5,753,706 Priority Date
1998-05-19 U.S. Patent No. 5,753,706 Issued
2003-02-19 U.S. Patent No. 7,767,851 Priority Date
2003-02-19 U.S. Patent No. 8,093,423 Priority Date
2003-02-19 U.S. Patent No. 8,299,298 Priority Date
2003-02-19 U.S. Patent No. 8,338,642 Priority Date
2003-02-19 U.S. Patent No. 8,609,896 Priority Date
2003-02-19 U.S. Patent No. 8,754,257 Priority Date
2003-02-19 U.S. Patent No. 8,754,258 Priority Date
2003-02-19 U.S. Patent No. 8,846,976 Priority Date
2003-02-19 U.S. Patent No. 8,901,349 Priority Date
2003-02-19 U.S. Patent No. 9,050,316 Priority Date
2003-02-19 U.S. Patent No. 9,328,133 Priority Date
2003-02-19 U.S. Patent No. 9,757,416 Priority Date
2009-07-21 U.S. Patent No. 9,387,191 Priority Date
2010-08-03 U.S. Patent No. 7,767,851 Issued
2012-01-10 U.S. Patent No. 8,093,423 Issued
2012-10-30 U.S. Patent No. 8,299,298 Issued
2012-12-25 U.S. Patent No. 8,338,642 Issued
2013-12-17 U.S. Patent No. 8,609,896 Issued
2014-06-17 U.S. Patent No. 8,754,257 Issued
2014-06-17 U.S. Patent No. 8,754,258 Issued
2014-09-30 U.S. Patent No. 8,846,976 Issued
2014-12-02 U.S. Patent No. 8,901,349 Issued
2015-06-09 U.S. Patent No. 9,050,316 Issued
2016-05-03 U.S. Patent No. 9,328,133 Issued
2016-07-12 U.S. Patent No. 9,387,191 Issued
2017-09-12 U.S. Patent No. 9,757,416 Issued
2018-12-21 Defendants sent Paragraph IV Certification Notice Letter (no earlier than)
2019-02-01 Complaint Filed

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

U.S. Patent No. 5,753,706 - "Methods for Treating Renal Failure," Issued May 19, 1998

The Invention Explained

  • Problem Addressed: Patients with renal failure experience phosphate retention, as the kidneys are the primary route for phosphate excretion (Compl. Ex. A, ’706 Patent, col. 1:11-14). This can lead to secondary hyperparathyroidism and soft tissue calcification. Existing treatments using aluminum or calcium-based phosphate binders presented issues of toxicity or hypercalcemia, respectively (’706 Patent, col. 1:35-44).
  • The Patented Solution: The invention proposes an oral method of administering a ferric-containing compound, such as ferric citrate or ferric acetate, to bind with ingested phosphate in the digestive tract (’706 Patent, col. 2:11-20). This process forms an insoluble precipitate, preventing intestinal absorption of the phosphate. The patent also notes that absorbed citrate can be converted to bicarbonate, helping to correct metabolic acidosis common in renal failure (’706 Patent, col. 2:33-38).
  • Technical Importance: The invention provided a method for phosphate binding that avoided the known side effects associated with aluminum and calcium-based compounds, offering a potentially safer therapeutic option for chronic kidney disease patients.

Key Claims at a Glance

  • The complaint asserts at least claims 1, 6, and 9 (Compl. ¶40). Independent claim 1 is asserted.
  • Claim 1 (Method):
    • A method of controlling phosphate retention in a patient suffering from hyperphosphatemia or predisposed to developing a hyperphosphatemic condition,
    • comprising the step of administering to the patient a therapeutically-effective amount of a compound selected from the group consisting of ferric citrate, ferric acetate and combinations thereof.
  • The complaint does not explicitly reserve the right to assert dependent claims but asserts "one or more claims" (Compl. ¶40).

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: Commercially available forms of ferric citrate have slow dissolution rates, requiring a substantially large oral dose to be effective as a phosphate binder (Compl. Ex. B, ’851 Patent, col. 1:49-59). This can impact patient compliance and therapeutic efficacy.
  • The Patented Solution: The invention discloses a novel form of ferric organic compounds, including ferric citrate, that is soluble over a wider pH range and has a large active surface area (’851 Patent, Abstract). The patent describes a specific synthesis method involving the addition of an alkaline metal hydroxide to a ferric iron salt to form a uniform polyiron oxo colloidal suspension, which is then processed to precipitate an amorphous ferric-organic acid compound with enhanced dissolution properties (’851 Patent, col. 2:22-42; Fig. 1).
  • Technical Importance: By creating a more soluble form of ferric citrate with a larger surface area, the invention suggests the possibility of achieving the desired phosphate-binding effect with a lower dose, potentially improving patient tolerability and treatment outcomes.

Key Claims at a Glance

  • The complaint asserts at least claim 1 (Compl. ¶49). Independent claim 1 is asserted.
  • Claim 1 (Composition of Matter):
    • 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 specified multi-step method.
  • The complaint asserts "one or more of the claims" (Compl. ¶49).

Multi-Patent Capsule: U.S. Patent No. 8,093,423

  • 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 (Compl. ¶11).
  • Technology Synopsis: This patent describes a manufacturing and quality control process for producing pharmaceutical-grade ferric citrate that consistently complies with established specifications. The process aims to provide a scalable method for producing ferric citrate suitable for human use, addressing the need for consistent quality in large-scale production (Compl. Ex. C, ’423 Patent, col. 2:1-8).
  • Asserted Claims: At least claims 1-7 (Compl. ¶56).
  • Accused Features: The Defendant's "Proposed Product" is alleged to infringe (Compl. ¶56).

Multi-Patent Capsule: U.S. Patent No. 8,299,298

  • Patent Identification: U.S. Patent No. 8,299,298, "Pharmaceutical-Grade Ferric Organic Compounds, Uses Thereof and Method of Making Same," Issued October 30, 2012 (Compl. ¶12).
  • Technology Synopsis: This patent, related to the '423 patent, also discloses manufacturing processes for pharmaceutical-grade ferric citrate. It claims ferric citrate compositions with a specific BET active surface area (at least 16 sq. m/g) and methods of treating hyperphosphatemia with these compositions (Compl. Ex. D, ’298 Patent, cl. 1, 8).
  • Asserted Claims: At least claim 1 (Compl. ¶64).
  • Accused Features: The Defendant's "Proposed Product" is alleged to infringe (Compl. ¶64).

Multi-Patent Capsule: U.S. Patent No. 8,338,642

  • Patent Identification: U.S. Patent No. 8,338,642, "Ferric Organic Compounds, Uses Thereof and Methods of Making Same," Issued December 25, 2012 (Compl. ¶13).
  • Technology Synopsis: This patent, related to the '851 patent family, claims an orally administrable form of ferric citrate prepared from a form having a specified intrinsic dissolution rate. It focuses on the therapeutic composition itself, derived from the novel forms of ferric citrate with enhanced solubility (Compl. Ex. E, ’642 Patent, cl. 1).
  • Asserted Claims: At least claims 1, 8-10, and 17-18 (Compl. ¶71).
  • Accused Features: The Defendant's "Proposed Product" is alleged to infringe (Compl. ¶71).

Multi-Patent Capsule: U.S. Patent No. 8,609,896

  • Patent Identification: U.S. Patent No. 8,609,896, "Ferric Organic Compounds, Uses Thereof and Methods of Making Same," Issued December 17, 2013 (Compl. ¶14).
  • Technology Synopsis: This patent is also in the '851 patent family and claims methods of treating hyperphosphatemia by administering the specifically defined, high-surface-area ferric citrate. It focuses on the method of use for the novel composition (Compl. Ex. F, ’896 Patent, cl. 1).
  • Asserted Claims: At least claim 1 (Compl. ¶80).
  • Accused Features: The Defendant's "Proposed Product" is alleged to infringe through its intended use (Compl. ¶80).

Multi-Patent Capsule: U.S. Patent Nos. 8,754,257 & 8,754,258

  • Patent Identification: U.S. Patent Nos. 8,754,257 and 8,754,258, both titled "Pharmaceutical-Grade Ferric Organic Compounds, Uses Thereof and Methods of Making Same," Issued June 17, 2014 (Compl. ¶¶15-16).
  • Technology Synopsis: These related patents claim pharmaceutical compositions of ferric citrate with specified high intrinsic dissolution rates and methods of treating hyperphosphatemia by administering them. They build on the earlier patents by claiming compositions and methods tied to the specific physical properties of the improved ferric citrate (Compl. Exs. G & H).
  • Asserted Claims: At least claim 1 of each patent (Compl. ¶¶87, 94).
  • Accused Features: The Defendant's "Proposed Product" is alleged to infringe (Compl. ¶¶87, 94).

Multi-Patent Capsule: U.S. Patent Nos. 8,846,976 & 8,901,349

  • Patent Identification: U.S. Patent Nos. 8,846,976 and 8,901,349, both titled "Ferric Organic Compounds, Uses Thereof and Methods of Making Same," Issued September 30, 2014 and December 2, 2014, respectively (Compl. ¶¶17-18).
  • Technology Synopsis: These patents, also in the '851 family, continue to claim methods of treating hyperphosphatemia and the specific, high-surface-area ferric citrate compositions used therein. The claims are directed to both the method and the composition with specific physical properties (Compl. Exs. I & J).
  • Asserted Claims: At least claim 1 of each patent (Compl. ¶¶101, 109).
  • Accused Features: The Defendant's "Proposed Product" is alleged to infringe (Compl. ¶¶101, 109).

Multi-Patent Capsule: U.S. Patent Nos. 9,050,316 & 9,757,416

  • Patent Identification: U.S. Patent Nos. 9,050,316 and 9,757,416, both titled "Pharmaceutical-Grade Ferric Organic Compounds, Uses Thereof and Methods of Making Same," Issued June 9, 2015 and September 12, 2017, respectively (Compl. ¶¶19, 22).
  • Technology Synopsis: These patents continue to claim methods and compositions related to pharmaceutical-grade ferric citrate, focusing on specific characteristics and treatment protocols for chronic kidney disease (Compl. Exs. K & N).
  • Asserted Claims: ’316 Patent: at least claims 1 and 12. ’416 Patent: at least claims 1, 12, 23, and 30 (Compl. ¶¶117, 141).
  • Accused Features: The Defendant's "Proposed Product" is alleged to infringe (Compl. ¶¶117, 141).

Multi-Patent Capsule: U.S. Patent Nos. 9,328,133 & 9,387,191

  • Patent Identification: U.S. Patent No. 9,328,133, "Ferric Organic Compounds, Uses Thereof and Methods of Making Same," Issued May 3, 2016; and U.S. Patent No. 9,387,191, "Ferric Citrate Dosage Forms," Issued July 12, 2016 (Compl. ¶¶20-21).
  • Technology Synopsis: The ’133 patent continues the theme of high-surface-area ferric citrate compositions and their use. The ’191 patent is directed to specific ferric citrate tablet formulations that meet certain dissolution, tableting, and disintegration standards, claiming tablets with at least 65% ferric citrate by weight and specific binders (Compl. Exs. L & M; '191 Patent, Abstract).
  • Asserted Claims: '133 Patent: at least claims 1, 8-10, and 17-18. '191 Patent: at least claims 1, 6, 11, and 16 (Compl. ¶¶125, 134).
  • Accused Features: The Defendant's "Proposed Product" is alleged to infringe (Compl. ¶¶125, 134).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is "Chemo's Proposed Product," an unmarketed generic version of Keryx's AURYXIA® (Ferric Citrate) Tablets for which Defendants have filed ANDA No. 212738 with the FDA (Compl. ¶1, 33).
  • Functionality and Market Context: The Proposed Product is a pharmaceutical tablet containing ferric citrate as its active ingredient (Compl. ¶1). It is intended for the same therapeutic uses as AURYXIA®, which is FDA-approved 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. ¶23). By filing an ANDA, Defendants are seeking to market their product as a bioequivalent and therapeutically equivalent substitute for the branded AURYXIA® drug before the expiration of the patents-in-suit (Compl. ¶1, 33, 36).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed claim chart or specific, element-by-element infringement allegations. The infringement theory is based on the statutory act of infringement under 35 U.S.C. § 271(e)(2)(A), which provides that submitting an ANDA for a drug claimed in a patent is an act of infringement. The complaint alleges that upon approval, the commercial manufacture, use, or sale of Chemo's Proposed Product will directly infringe the asserted patents (Compl. ¶42, 51).

  • 5,753,706 Infringement Allegations
Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of controlling phosphate retention in a patient suffering from hyperphosphatemia or a patient predisposed to development of a hyperphosphatemic condition, The complaint alleges that Defendants' Proposed Product is a generic version of AURYXIA®, a drug used to control serum phosphorus, and its use will therefore constitute this method (Compl. ¶¶1, 23, 40). ¶40 col. 2:11-20
comprising the step of administering to the patient a therapeutically-effective amount of a compound selected from the group consisting of ferric citrate, ferric acetate and combinations thereof. The Proposed Product is a ferric citrate tablet, which, when administered as directed by its proposed labeling, will provide a therapeutically-effective amount of ferric citrate for controlling phosphate retention (Compl. ¶¶1, 40). ¶40 col. 2:11-20

  • Identified Points of Contention:

    • Scope Questions: A potential dispute may arise over whether the proposed label for the generic product will instruct users to perform the specific steps of "controlling phosphate retention" as recited in the claim, which is central to establishing induced infringement of this method claim.
    • Technical Questions: Since the complaint is based on the ANDA filing, a key question for the court will be whether the characteristics of the actual proposed generic product, once revealed in discovery, fall within the scope of what is meant by "ferric citrate" as used in the patent, particularly if its chemical form, purity, or isomer content differs from that contemplated by the patent.

  • 7,767,851 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
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, The complaint alleges that the Proposed Product is a generic ferric citrate tablet that infringes the asserted claims, implying it possesses the claimed chemical formula and physical properties (Compl. ¶49). ¶49 col. 2:50-56
wherein the solid form of ferric citrate is synthesized by a method comprising... [multi-step synthesis process] The complaint’s allegation of infringement implies that the method of manufacturing the Proposed Product is the same as or equivalent to the claimed synthesis method, or results in a product with identical claimed properties (Compl. ¶49). ¶49 col. 2:22-42
  • Identified Points of Contention:
    • Scope Questions: The analysis will likely focus on whether the term "synthesized by a method comprising" requires the accused infringer to perform the exact recited steps, or if it can be read as a product-by-process claim where the structure and properties of the final product are determinative, regardless of the manufacturing process.
    • Technical Questions: A central evidentiary question will be whether Defendants' generic product actually has an "intrinsic dissolution rate between 1.9 and 4.0 mg/cm²/min." This is a precise, quantifiable property that will require expert testing and analysis of the accused product.

V. Key Claim Terms for Construction

  • The Term: "a compound selected from the group consisting of ferric citrate, ferric acetate and combinations thereof" (’706 Patent, cl. 1)

    • Context and Importance: This term defines the active pharmaceutical ingredient. Practitioners may focus on this term because the precise chemical nature of the ferric citrate in the accused product—including its hydration state, isomeric form, or the presence of related substances—could be a basis for a non-infringement argument if it is alleged to fall outside the patent's definition of "ferric citrate."
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claim uses the general chemical name "ferric citrate" without specifying a particular crystalline form, hydration state, or purity level, which may support an interpretation covering any substance chemically identifiable as ferric citrate (’706 Patent, col. 2:15-16).
      • Evidence for a Narrower Interpretation: The specification describes experiments with a specific form of ferric citrate (FeC6H5O7, M.W. 245), which could be used to argue that the claims are limited to the specific forms of ferric citrate disclosed and tested in the patent (’706 Patent, col. 4:18-19).

  • The Term: "a solid form of ferric citrate having... an intrinsic dissolution rate between 1.9 and 4.0 mg/cm²/min" (’851 Patent, cl. 1)

    • Context and Importance: This quantitative limitation is critical to distinguishing the claimed invention from prior art ferric citrate, which the patent describes as having slow dissolution (’851 Patent, col. 1:56-57). The infringement analysis for this patent family will likely depend heavily on whether the accused product's dissolution rate falls within this specific numerical range.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claim covers a "form" of ferric citrate with this property, suggesting that any physical form (e.g., amorphous, different polymorphs) that meets the dissolution rate would infringe, not just the specific form created by the patent's examples (’851 Patent, cl. 11).
      • Evidence for a Narrower Interpretation: The patent attributes the enhanced dissolution rate to the specific synthesis method described, which creates a large active surface area (’851 Patent, col. 1:36-42). This suggests the dissolution rate is intrinsically tied to the novel form produced by the disclosed process, potentially narrowing the claim's scope to forms having the structural characteristics that result from that process.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for multiple method-of-use patents, including the ’706 Patent (Compl. ¶¶43-44). The allegations are based on the assertion that Defendants know of the patents and that their Proposed Product is specifically designed for the infringing use (i.e., the labeled indications), lacks substantial non-infringing uses, and that Defendants will intentionally encourage infringement through their marketing and labeling upon FDA approval.
  • Willful Infringement: The complaint does not use the term "willful," but for each asserted patent it alleges that the case is "an exceptional one" and requests an award of attorneys' fees under 35 U.S.C. § 285 (Compl. ¶47, 54, 62, etc.). These allegations are predicated on Defendants' knowledge of the patents-in-suit, established by the patents' listing in the FDA's Orange Book for AURYXIA® and by Defendants' service of a Paragraph IV Notice Letter, which explicitly addresses the patents (Compl. ¶¶24, 36).

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

This litigation presents a classic Hatch-Waxman dispute, which will likely turn on three central questions for the court:

  • A primary question will be one of validity: Defendants' Paragraph IV certification asserts that the patents-in-suit are invalid or unenforceable. Consequently, a core part of the case will involve Defendants' attempts to prove, by clear and convincing evidence, that the claims are invalid, for instance, as being anticipated by or obvious over the prior art.
  • A key evidentiary question will be one of physical and chemical properties: For the numerous composition-of-matter patents, the dispute will center on whether the Defendants' generic product possesses the specific, quantitative characteristics required by the claims, such as the intrinsic dissolution rate and BET active surface area. This will necessitate extensive discovery and competing expert testimony on the physical nature of the accused product.
  • A critical legal issue will be one of induced infringement: For the asserted method-of-use patents, the analysis will focus on whether the language in the proposed label for the generic product will be found to actively instruct or encourage medical professionals and patients to administer the drug in a manner that performs all steps of the claimed methods.