DCT

1:20-cv-00484

Chiesi USA Inc v. Hikma Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:20-cv-00484, D. Del., 04/08/2020
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware based on Hikma USA and EuroHealth being Delaware corporations. For Hikma PLC, a foreign entity, the complaint asserts that federal venue statutes do not apply. The complaint also alleges that all defendants have continuous and systematic contacts with Delaware and that the submission of the Abbreviated New Drug Application (ANDA) constitutes an act of infringement in the district.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an ANDA to the FDA seeking approval to market a generic version of Plaintiff's Ferriprox® (deferiprone) tablets constitutes an act of infringement of a patent covering a method of using the drug to treat iron-induced cardiac disease.
  • Technical Context: The dispute involves an oral iron chelation therapy used to treat transfusional iron overload, a serious condition often resulting from treatments for thalassemia, which can lead to fatal cardiac complications.
  • Key Procedural History: This is a Hatch-Waxman action triggered by Defendants' filing of an ANDA with a Paragraph IV certification, challenging U.S. Patent No. 7,049,328, which is listed in the FDA's Orange Book for the Ferriprox® product. The inventor filed a disclaimer for claim 3 of the patent on September 11, 2017.

Case Timeline

Date Event
2000-06-30 ’328 Patent Priority Date
2006-05-23 ’328 Patent Issue Date
2017-09-11 Disclaimer filed for Claim 3 of '328 Patent
2020-01-08 Chiesi Farmaceutici S.p.A. acquires ’328 Patent
2020-02-25 Plaintiff receives Defendants' Paragraph IV Notice Letter
2020-04-08 Complaint Filing Date
2021-06-28 ’328 Patent Expiration Date (per complaint)

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

U.S. Patent No. 7,049,328 - "Use For Deferiprone"

  • Patent Identification: U.S. Patent No. 7,049,328, "Use For Deferiprone", issued May 23, 2006.

The Invention Explained

  • Problem Addressed: The patent’s background section describes that patients with conditions like thalassemia require regular blood transfusions, which leads to a dangerous iron overload in the body. While the standard injectable iron chelator, desferrioxamine, can reduce total body iron, a high level of premature cardiac deaths persists, suggesting that simply lowering the total iron load is "insufficient to protect against iron-induced heart damage" (’328 Patent, col. 2:51-54). Poor patient compliance with the difficult injectable regimen further complicates treatment (’328 Patent, col. 1:50-60).
  • The Patented Solution: The invention is a method of using deferiprone, an orally administered iron chelator, to specifically treat or prevent iron-induced cardiac disease. The patent asserts that deferiprone has an unexpected "cardio selective/preferred function" compared to other chelators (’328 Patent, col. 9:11-12). It proposes that deferiprone's chemical properties allow it to readily cross cell membranes and bind intracellular iron directly within heart muscle cells (myocytes), thus providing targeted protection beyond what is achieved by general iron reduction (’328 Patent, col. 11:12-23). Figure 2 of the patent presents a Kaplan-Meier survival curve purporting to show that deferiprone-treated patients had significantly better heart-disease-free survival than patients treated with desferrioxamine (’328 Patent, Fig. 2).
  • Technical Importance: The invention claims to provide an oral therapy that is not only more convenient for patients but is also specifically more effective at preventing the cardiac complications that are a leading cause of mortality in this patient population (’328 Patent, col. 2:10-18).

Key Claims at a Glance

  • The complaint asserts infringement of independent claims 1, 6, 7, 8, 9, and 10, along with dependent claims 2, 4, and 5 (Compl. ¶57). Claim 3 has been disclaimed.
  • Independent Claim 1, the broadest method claim, recites the following elements:
    • A method of treating iron induced cardiac disease
    • in a blood transfusion dependent patient
    • experiencing an iron overload condition of the heart
    • comprising administering to the patient a therapeutically effective amount of deferiprone or a physiologically acceptable salt thereof
    • sufficient to stabilize/reduce iron accumulation in the heart resulting from being transfusion dependent.
  • The complaint reserves the right to assert additional claims (’328 Patent, col. 18:18-20).

III. The Accused Instrumentality

Product Identification

  • Defendants' 500 mg deferiprone tablet, referred to as the "ANDA Product," for which Defendants submitted Abbreviated New Drug Application (ANDA) No. 213239 to the FDA (Compl. ¶¶14, 20).

Functionality and Market Context

  • The ANDA Product is a generic version of Plaintiff's Ferriprox® 500 mg deferiprone tablet, which is its reference listed drug (Compl. ¶51).
  • The complaint alleges that the proposed prescribing information for the ANDA Product will recommend its use for the same indication as Ferriprox®: "for the treatment of patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate" (Compl. ¶¶35, 42, 45).
  • It is further alleged that the ANDA Product's label will instruct for the same dosage and administration as Ferriprox® (75 mg/kg to 99 mg/kg total daily dose) and will teach the same clinical study results, which include data on the reduction of serum ferritin and an increase in cardiac MRI T2*, an indicator of reduced cardiac iron (Compl. ¶¶36, 37, 43, 44).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

Claim Chart Summary

The complaint does not contain a claim chart. The following table summarizes the infringement theory for Claim 1, which is based on induced infringement via the proposed product label.

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating iron induced cardiac disease... The proposed label for the ANDA Product will allegedly recommend the same "Indication and Usage" as Ferriprox®, which is for treating patients with transfusional iron overload, a condition the patent identifies as causing cardiac disease. ¶42, ¶45 col. 9:13-18
...in a blood transfusion dependent patient experiencing an iron overload condition of the heart... The alleged indication is for "transfusional iron overload," which by definition occurs in transfusion-dependent patients and, according to the patent, causes toxic degenerative changes in the heart. ¶35, ¶45 col. 1:24-31
...comprising administering to the patient a therapeutically effective amount of deferiprone... The ANDA Product is a 500 mg deferiprone tablet, and its label will allegedly recommend a daily dosage regimen identical to that of Ferriprox®. ¶44, ¶52 col. 10:55-63
...sufficient to stabilize/reduce iron accumulation in the heart resulting from being transfusion dependent. The ANDA Product's label will allegedly teach the same clinical study results as Ferriprox®, including data showing an "increase in cardiac MRI T2*," which the complaint presents as evidence of reduced iron in the heart. ¶36, ¶43 col. 16:1-12

Identified Points of Contention

  • Scope Questions: A central question may be whether instructing the use of deferiprone for "transfusional iron overload" is legally sufficient to induce infringement of a claim directed specifically to "treating iron induced cardiac disease." A defendant could argue that its label only addresses systemic iron levels and does not actively promote the specific cardiac treatment method claimed in the patent.
  • Technical Questions: The case will likely involve a dispute over whether the "cardio selective/preferred function" described in the patent specification is a real, non-obvious phenomenon. Defendants' Paragraph IV certification alleges invalidity (Compl. ¶40), raising the question of whether any observed cardiac benefit is merely an inherent, and therefore obvious, result of using any effective iron chelator in patients whose primary cause of death is iron-induced heart failure.

V. Key Claim Terms for Construction

  • The Term: "treating iron induced cardiac disease"
  • Context and Importance: The construction of this term is fundamental to both infringement and validity. Whether the ANDA label induces infringement depends on whether its instructions meet the definition of "treating" this specific condition. For validity, the question is whether this method was novel and non-obvious over prior art methods of treating general iron overload.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification repeatedly uses phrases like "prevention/stabilization/reduction of the risk of heart disease," which may support an interpretation that "treating" includes prophylactic or risk-reducing administration in patients not yet diagnosed with cardiac disease (’328 Patent, col. 9:41-43).
    • Evidence for a Narrower Interpretation: The claim language uses the word "treating," not "preventing." The patent also highlights data showing "improvement of the cardiac function" in patients who presumably already had a degree of cardiac dysfunction, which could support a narrower construction requiring an existing diagnosed condition (’328 Patent, col. 15:20-22).

VI. Other Allegations

Indirect Infringement

  • The complaint alleges that Defendants will induce infringement by physicians and patients. The basis for this claim is the allegation that the ANDA Product's prescribing information and label will actively instruct and encourage users to administer the 500 mg deferiprone tablet according to the indications, clinical findings, and dosage regimens of Ferriprox®, thereby directing them to perform the patented method (Compl. ¶¶42-44, 63).

Willful Infringement

  • The complaint alleges that Defendants had knowledge of the ’328 patent at least since filing their ANDA with its Paragraph IV certification (Compl. ¶¶41, 61). Willfulness is further alleged on the basis that Defendants' non-infringement and invalidity positions in their Notice Letter are "devoid of any objective good-faith basis" and that they acted "without a reasonable basis for believing that they would not be liable for infringing" (Compl. ¶¶62, 63).

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

  • A central question for the court will be one of validity and non-obviousness: Was the specific cardio-protective benefit of deferiprone, as claimed in the ’328 patent, an unexpected and non-obvious discovery, or was it merely an inherent and therefore obvious property of using an oral iron chelator to treat systemic iron overload in a patient population known to suffer from cardiac complications?
  • A key evidentiary question will concern induced infringement: Will the final, FDA-approved label for the Defendants’ generic product contain sufficiently specific data or instructions regarding cardiac effects to demonstrate an affirmative intent to encourage physicians to perform the patented method, or will the label be limited to claims about treating general iron overload, potentially falling short of inducing infringement of the specific method claims?