DCT

1:19-cv-00040

Keryx Biopharma Inc v. Mylan Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-00040, N.D. W. Va., 03/15/2019
  • Venue Allegations: Venue is alleged to be proper as Defendant is a corporation organized under the laws of West Virginia with its principal place of business in the district.
  • 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 infringement of fourteen patents covering the drug composition and methods of use.
  • Technical Context: The technology concerns ferric citrate, an iron-based, non-calcium, non-aluminum phosphate binder used to control serum phosphorus levels in patients with chronic kidney disease.
  • Key Procedural History: The action arises under the Hatch-Waxman Act, triggered by Defendant’s filing of ANDA No. 212834 with a Paragraph IV certification alleging that Plaintiffs’ patents are invalid, unenforceable, and/or will not be infringed. The complaint was filed within the 45-day statutory window following receipt of Defendant's notice letter, initiating a 30-month stay on FDA approval of the ANDA.

Case Timeline

Date Event
1996-12-16 ’706 Patent Priority Date
1998-05-19 U.S. Patent No. 5,753,706 Issued
2003-02-19 Earliest Priority Date for ’851, ’423, ’298, ’642, ’896, ’257, ’258, ’976, ’349, ’316, ’133, and ’416 Patents
2005-08-19 ’191 Patent 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
2019-02-04 Plaintiffs’ receipt of Defendant’s ANDA Notice Letter (at the earliest)
2019-03-15 Complaint Filing Date

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

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

The Invention Explained

  • Problem Addressed: The patent describes that patients with renal failure inevitably experience phosphate retention (hyperphosphatemia), as the kidneys are the primary route of phosphate excretion (’706 Patent, col. 1:11-13). For decades, treatments involved aluminum-based compounds, which raised toxicity concerns, or calcium-based compounds, which could lead to excessive calcium levels in end-stage renal disease patients (’706 Patent, col. 1:35-44).
  • The Patented Solution: The invention proposes an oral method of treatment using ferric-containing compounds, specifically ferric citrate and ferric acetate, to bind with dietary phosphate in the digestive tract (’706 Patent, Abstract). This binding action forms an insoluble precipitate, preventing the phosphate from being absorbed into the bloodstream (’706 Patent, col. 2:30-34). An additional benefit described is that the citrate or acetate component, once absorbed, is converted to bicarbonate, which helps correct the metabolic acidosis also common in renal failure patients (’706 Patent, col. 2:25-28, 35-38).
  • Technical Importance: The invention offered a therapeutic alternative that avoided the toxicities associated with aluminum and the calcium-loading issues of then-prevalent phosphate binders.

Key Claims at a Glance

  • The complaint asserts independent claims 1 and 6 (Compl. ¶33).
  • Independent Claim 1 contains the following essential elements:
    • A method of controlling phosphate retention in a patient suffering from hyperphosphatemia or a patient predisposed to development of 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.
  • Independent Claim 6 contains the following essential elements:
    • A therapeutic composition in oral dosage form for controlling phosphate retention in patients having need for reduced absorption of dietary phosphate,
    • said composition comprising on a per dose basis from about 500 mg to about 1000 mg of a compound selected from the group consisting of ferric citrate, ferric acetate and combinations thereof, and
    • a pharmaceutically acceptable excipient for said oral dosage form.

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

The Invention Explained

  • Problem Addressed: The patent notes that prior forms of ferric citrate, such as the crystalline form disclosed in the ’706 Patent, have a slow dissolution rate (’851 Patent, col. 1:52-54). This slow dissolution requires patients to take substantially large oral doses to be effective, which can impact patient compliance and lead to side effects (’851 Patent, col. 1:49-57).
  • The Patented Solution: The invention discloses a novel, amorphous form of ferric citrate with a significantly enhanced dissolution rate and a large active surface area (’851 Patent, Abstract). This form is produced through a specific synthesis method, which involves reacting a soluble ferric iron salt with an alkaline metal hydroxide to form a precipitate, and then reacting that precipitate with a crystalline organic acid (like citric acid) before precipitating the final compound with an organic solvent (’851 Patent, col. 2:22-42; Fig. 1).
  • Technical Importance: By creating a more soluble form of ferric citrate, the invention suggests the possibility of achieving therapeutic efficacy with lower doses, potentially improving patient compliance and reducing adverse gastrointestinal effects.

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶42).
  • Independent Claim 1 contains the following essential elements:
    • 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 specific steps (a) through (e), including adding an alkaline metal hydroxide to a ferric chloride solution and precipitating the final product with an organic solvent.

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. ¶8).
  • Technology Synopsis: This patent, a continuation of the '851 patent, further describes the manufacturing and quality control processes for producing a "pharmaceutical-grade" ferric citrate that consistently complies with established specifications. The invention addresses the need for a scalable process to produce ferric citrate suitable for human use with controlled purity and physical properties (’423 Patent, col. 1:62-col. 2:4).
  • Asserted Claims: Independent claim 7 (Compl. ¶49).
  • Accused Features: Mylan's proposed generic ferric citrate tablets are accused of infringement (Compl. ¶49).

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. ¶9).
  • Technology Synopsis: As a continuation of the '423 patent, this patent claims a form of ferric citrate with a specific BET active surface area exceeding 16 sq. m/g. This property is linked to the enhanced dissolution rate that distinguishes it from prior crystalline forms and is a key feature of the pharmaceutical-grade compound (’298 Patent, Abstract; col. 1:55-61).
  • Asserted Claims: Independent claim 1 (Compl. ¶57).
  • Accused Features: Mylan's proposed generic ferric citrate tablets are accused of infringement (Compl. ¶57).

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. ¶10).
  • Technology Synopsis: This patent is a continuation of the application that led to the '851 patent and claims the specific form of ferric citrate produced by the novel synthesis method. The claims cover the product defined by its unique manufacturing process, which imparts the desirable solubility characteristics (’642 Patent, col. 1:5-10; Abstract).
  • Asserted Claims: Independent claims 1, 8, 10, and 17 (Compl. ¶64).
  • Accused Features: Mylan's proposed generic ferric citrate tablets are accused of infringement (Compl. ¶64).

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. ¶11).
  • Technology Synopsis: This patent, another continuation in the same family, claims an orally administrable form of ferric citrate prepared from a precursor material having a high BET active surface area. This links the final drug product back to the novel physical properties of the active pharmaceutical ingredient created by the patented synthesis process (’896 Patent, col. 1:5-10; Abstract).
  • Asserted Claims: Independent claim 1 (Compl. ¶73).
  • Accused Features: Mylan's proposed generic ferric citrate tablets are accused of infringement (Compl. ¶73).

Multi-Patent Capsule: U.S. Patent No. 8,754,257

  • Patent Identification: U.S. Patent No. 8,754,257, "Pharmaceutical-Grade Ferric Organic Compounds, Uses Thereof and Methods of Making Same," issued June 17, 2014 (Compl. ¶12).
  • Technology Synopsis: This patent is a divisional of the application that led to the '423 patent. It claims methods of treating hyperphosphatemia by administering a pharmaceutical composition containing ferric citrate with a specific intrinsic dissolution rate, directly tying the therapeutic method to the novel physical properties of the drug substance (’257 Patent, col. 1:12-19; Abstract).
  • Asserted Claims: Independent claim 1 (Compl. ¶80).
  • Accused Features: Mylan's proposed generic ferric citrate tablets are accused of infringement (Compl. ¶80).

Multi-Patent Capsule: U.S. Patent No. 8,754,258

  • Patent Identification: U.S. Patent No. 8,754,258, "Ferric Organic Compounds, Uses Thereof and Methods of Making Same," issued June 17, 2014 (Compl. ¶13).
  • Technology Synopsis: This patent is a continuation of the application that led to the '896 patent. It claims an orally administrable form of ferric citrate where the intrinsic dissolution rate is measured by the specific USP assay, reinforcing the patentability of the compound's specific, measurable physical properties that distinguish it from the prior art (’258 Patent, Abstract).
  • Asserted Claims: Independent claim 1 (Compl. ¶87).
  • Accused Features: Mylan's proposed generic ferric citrate tablets are accused of infringement (Compl. ¶87).

Multi-Patent Capsule: U.S. Patent No. 8,846,976

  • Patent Identification: U.S. Patent No. 8,846,976, "Ferric Organic Compounds, Uses Thereof and Methods of Making Same," issued September 30, 2014 (Compl. ¶14).
  • Technology Synopsis: This patent, a continuation of the application that led to the '258 patent, claims a method of treating hyperphosphatemia by administering the orally administrable form of ferric citrate that is prepared from the high-surface-area precursor. The claims tie the method of treatment directly to the novel form of the drug substance (’976 Patent, Abstract).
  • Asserted Claims: Independent claim 1 (Compl. ¶94).
  • Accused Features: Mylan's proposed generic ferric citrate tablets are accused of infringement (Compl. ¶94).

Multi-Patent Capsule: U.S. Patent No. 8,901,349

  • Patent Identification: U.S. Patent No. 8,901,349, "Ferric Organic Compounds, Uses Thereof and Methods of Making Same," issued December 2, 2014 (Compl. ¶15).
  • Technology Synopsis: A continuation of the application that led to the '976 patent, this patent focuses on a method of treating hyperphosphatemia where the administered ferric citrate has the specific intrinsic dissolution rate of 1.88-4.0 mg/cm²/min. This again links the therapeutic method claim to the specific physical property of the novel drug form (’349 Patent, Abstract).
  • Asserted Claims: Independent claim 1 (Compl. ¶102).
  • Accused Features: Mylan's proposed generic ferric citrate tablets are accused of infringement (Compl. ¶102).

Multi-Patent Capsule: U.S. Patent No. 9,050,316

  • Patent Identification: U.S. Patent No. 9,050,316, "Pharmaceutical-Grade Ferric Organic Compounds, Uses Thereof and Methods of Making Same," issued June 9, 2015 (Compl. ¶16).
  • Technology Synopsis: This patent is a continuation of the application that led to the '257 patent. It claims a pharmaceutical composition comprising the novel form of ferric citrate with the specified intrinsic dissolution rate, focusing on the composition itself rather than the method of treatment (’316 Patent, Abstract).
  • Asserted Claims: Independent claims 1 and 12 (Compl. ¶110).
  • Accused Features: Mylan's proposed generic ferric citrate tablets are accused of infringement (Compl. ¶110).

Multi-Patent Capsule: U.S. Patent No. 9,328,133

  • Patent Identification: U.S. Patent No. 9,328,133, "Ferric Organic Compounds, Uses Thereof and Methods of Making Same," issued May 3, 2016 (Compl. ¶17).
  • Technology Synopsis: As a continuation of the application leading to the '642 patent, this patent claims the solid form of ferric citrate having the specified intrinsic dissolution rate. The claims focus on the product-by-process and resulting physical properties of the novel ferric citrate material (’133 Patent, Abstract).
  • Asserted Claims: Independent claims 1, 8, 10, and 17 (Compl. ¶118).
  • Accused Features: Mylan's proposed generic ferric citrate tablets are accused of infringement (Compl. ¶118).

Multi-Patent Capsule: U.S. Patent No. 9,387,191

  • Patent Identification: U.S. Patent No. 9,387,191, "Ferric Citrate Dosage Forms," issued July 12, 2016 (Compl. ¶18).
  • Technology Synopsis: This patent shifts focus to the final dosage form, claiming a tablet that includes ferric citrate and a binder, where the formulation exhibits specific dissolution, hardness, and disintegration properties. The invention addresses the technical challenges of formulating the novel ferric citrate into a robust, immediate-release tablet (’191 Patent, Abstract; col. 2:45-50).
  • Asserted Claims: Independent claims 1, 6, 11, and 16 (Compl. ¶127).
  • Accused Features: Mylan's proposed generic ferric citrate tablets are accused of infringement (Compl. ¶127).

Multi-Patent Capsule: U.S. Patent No. 9,757,416

  • Patent Identification: U.S. Patent No. 9,757,416, "Pharmaceutical-Grade Ferric Organic Compounds, Uses Thereof and Methods of Making Same," issued September 12, 2017 (Compl. ¶19).
  • Technology Synopsis: This patent is a continuation of the application that led to the '316 patent. It claims a method of treating hyperphosphatemia by administering a tablet containing the novel form of ferric citrate. The claims link the therapeutic method to the specific dosage form having the advantageous properties (’416 Patent, Abstract).
  • Asserted Claims: Independent claims 1 and 23 (Compl. ¶134).
  • Accused Features: Mylan's proposed generic ferric citrate tablets are accused of infringement (Compl. ¶134).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is "Mylan's Proposed Product," which is a generic version of AURYXIA® (Ferric Citrate) Tablets for which Defendant Mylan submitted Abbreviated New Drug Application (ANDA) No. 212834 to the FDA (Compl. ¶1).

Functionality and Market Context

The complaint alleges that Mylan's Proposed Product is a generic version of Keryx's AURYXIA®, an orally available, iron-based medicine approved for controlling serum phosphorus levels in adult patients with chronic kidney disease on dialysis (Compl. ¶20). By filing the ANDA, Mylan seeks FDA approval to commercially manufacture and sell this generic product in the United States prior to the expiration of the patents-in-suit (Compl. ¶26). The act of filing the ANDA, which certifies that the generic will have the same active ingredient, dosage form, and route of administration as the branded drug, is the statutory act of infringement under 35 U.S.C. § 271(e)(2).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint alleges infringement of all fourteen patents-in-suit through the submission of ANDA No. 212834, but does not provide specific technical evidence, such as test results or product specifications, to map the accused product to the claim elements. The infringement theory appears to be based on the statutory presumption that a generic product seeking approval as a therapeutic equivalent to a branded drug will practice the patents covering that drug.

‘706 Patent 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, Mylan's proposed product is a generic version of AURYXIA®, which is FDA-approved for the control of serum phosphorus levels in patients with chronic kidney disease. Mylan allegedly encourages this use. ¶20, ¶36 col. 10:25-27
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. Mylan's proposed product is a ferric citrate tablet intended for oral administration to patients. ¶1, ¶36 col. 10:27-30
  • Identified Points of Contention:
    • Scope Questions: A potential dispute may arise over whether Mylan’s proposed labeling and instructions will induce administration specifically for "controlling phosphate retention" as required by claim 1, particularly as the branded drug also has an indication for treating iron deficiency anemia (Compl. ¶20), which is not explicitly claimed.
    • Technical Questions: For the composition claim 6, a question will be whether the dosage of Mylan’s product, as prescribed, delivers "from about 500 mg to about 1000 mg" of ferric citrate per dose.

‘851 Patent 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... The complaint alleges on information and belief that Mylan's proposed ferric citrate product will meet the claimed physical property of intrinsic dissolution rate. ¶42, ¶44 col. 12:1-4
wherein the solid form of ferric citrate is synthesized by a method comprising [steps (a)-(e)]... The complaint alleges on information and belief that Mylan's product is or will be made by a process that meets the claimed synthesis steps. ¶42, ¶44 col. 12:5-16
  • Identified Points of Contention:
    • Technical Questions: The central issue will be evidentiary. What is the actual "intrinsic dissolution rate" of Mylan's proposed product? The complaint does not provide data to support this allegation.
    • Scope Questions: Does the process Mylan uses to manufacture its ferric citrate fall within the scope of the method steps recited in claim 1? The infringement allegation is a product-by-process claim, which will require discovery into Mylan's confidential manufacturing information contained in the ANDA.

V. Key Claim Terms for Construction

  • The Term: "therapeutically-effective amount" (’706 Patent, Claim 1)

    • Context and Importance: The definition of this term is critical for the method claims, as it links the administration of the compound to a therapeutic outcome. Practitioners may focus on this term because its meaning depends on the specific condition being treated—"controlling phosphate retention"—which Mylan may argue is not the sole or primary purpose for which its generic drug will be prescribed.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification suggests an amount "effective to achieve a selected desired result," which is broadly defined as a "clinically observable reduction in absorption of ingested phosphate and/or a correction in metabolic acidosis" (’706 Patent, col. 3:14-19).
      • Evidence for a Narrower Interpretation: The patent provides specific daily dosage examples, such as "about 5 g to about 10 g," which could be argued to define the scope of what the inventor considered effective (’706 Patent, col. 3:21-22).

  • The Term: "intrinsic dissolution rate" (’851 Patent, Claim 1)

    • Context and Importance: This quantitative physical property is the primary feature distinguishing the claimed invention from prior art crystalline forms of ferric citrate. The entire infringement analysis for the '851 patent and many of its progeny will depend on whether Mylan's product falls within the recited numerical range of 1.9 to 4.0 mg/cm²/min.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification presents a range of experimental results showing dissolution rates for different batches, which may support some flexibility in interpreting the boundaries of the claimed range (’851 Patent, Table 3).
      • Evidence for a Narrower Interpretation: The claim explicitly states the rate is "as determined by the USP intrinsic dissolution assay in water" (’851 Patent, col. 12:3-5). This ties the claim term directly to a standardized, well-defined measurement protocol, which may support a strict interpretation of the numerical values obtained using that specific test.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement of infringement for the asserted method claims (e.g., Compl. ¶36). The basis for this allegation is that Mylan, through its product labeling, marketing, and instructions, will encourage and instruct healthcare providers and patients to administer the proposed generic product in a manner that directly infringes the method claims of the patents-in-suit, with knowledge of those patents.
  • Willful Infringement: The complaint does not explicitly allege "willful" infringement. However, it alleges that Mylan has knowledge of the patents-in-suit and, in each count, states that the case is "an exceptional one" and requests an award of attorneys' fees under 35 U.S.C. § 285 (e.g., Compl. ¶¶ 36, 40, 47). Such a request is often predicated on conduct that could be considered willful or otherwise egregious.

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

  • A key evidentiary question will be one of physical characterization: does Mylan’s proposed generic product, as detailed in its confidential ANDA, possess the specific intrinsic dissolution rates and BET active surface areas claimed in the ’851 patent family? The complaint’s allegations are based on the statutory act of infringement, and the case will require technical discovery to determine if the accused product literally meets these quantitative limitations.
  • A central issue of infringement for the method claims will be one of induced infringement: can Plaintiffs establish that Mylan's proposed product label will instruct or encourage administration for the specific patented purpose of controlling phosphate retention, as opposed to other potential uses such as treating iron deficiency anemia, for which the branded drug is also approved?
  • With a large family of fourteen asserted patents stemming from common priority applications, a core issue for the defense will likely be validity: Mylan may challenge the patents on grounds of obviousness-type double patenting or argue that the claims of later-issued patents are invalid as obvious over the disclosures of the earlier patents in the same family.