DCT

1:23-cv-01189

ZS Pharma Inc v. AstraZeneca Pharma LP

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-01189, D. Del., 10/20/2023
  • Venue Allegations: Venue is alleged to be proper for Lupin Pharmaceuticals, Inc. as a Delaware corporation and for Lupin Limited as an alien corporation subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the hyperkalemia drug LOKELMA® constitutes an act of infringement of a patent covering low-impurity pharmaceutical compositions.
  • Technical Context: The technology relates to zirconium silicate compositions used as potassium binders to treat hyperkalemia, a condition of elevated potassium in the blood, where the compositions are specifically formulated to have very low lead content for safe, extended-term use.
  • Key Procedural History: This action was filed under the Hatch-Waxman Act following Defendants' submission of ANDA No. 217549 and a corresponding Paragraph IV certification for the patent-in-suit. The complaint notes the patent issued after the ANDA was filed but cites Federal Circuit precedent that this does not preclude infringement liability. The parties have engaged in prior litigation (Civil Action No. 22-1055) concerning the same ANDA and other patents in the same family.

Case Timeline

Date Event
2015-10-14 '044 Patent Priority Date
2022-07-01 Defendants' "First Notice Letter" regarding other patents
2022-09-30 Defendants' "Second Notice Letter" regarding other patents
2023-08-29 '044 Patent Issue Date
2023-10-20 Complaint Filing Date

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

U.S. Patent No. 11,738,044 - "Extended Use Zirconium Silicate Compositions and Methods of Use Thereof"

  • Issued: August 29, 2023.

The Invention Explained

  • Problem Addressed: The patent describes the challenge of producing zirconium silicate compositions for treating hyperkalemia that are safe for long-term or extended administration (Compl. ¶21; ’044 Patent, col. 3:16-21). Specifically, it notes that producing these compositions at an industrial scale can result in unacceptable levels of heavy metal impurities, particularly lead, which is a significant safety concern for chronic-use drugs ('044 Patent, col. 3:21-34).
  • The Patented Solution: The invention is a method of treating hyperkalemia by administering a specific zirconium silicate composition that is characterized by having a lead content below a certain threshold (0.6 parts per million) ('044 Patent, Abstract; col. 8:36-61). The patent specification details manufacturing processes, such as using colloidal silica as a reactant and employing particular reactor configurations, designed to achieve this high level of purity at industrial scale ('044 Patent, col. 5:2-12; col. 7:1-9).
  • Technical Importance: Achieving exceptionally low lead levels is critical for pharmaceuticals intended for chronic use, as regulatory bodies impose strict limits on the total daily intake of such impurities ('044 Patent, col. 3:21-24).

Key Claims at a Glance

  • The complaint asserts infringement of one or more unspecified claims (Compl. ¶35). The first independent claim is Claim 1.
  • Independent Claim 1: A method claim with the following essential elements:
    • A method of treating hyperkalemia.
    • The method comprises administering a cation exchange composition "over a period of more than 5 consecutive days to a patient in need thereof."
    • The composition comprises a specific zirconium silicate of formula (I).
    • The composition "exhibits a lead content below 0.6 ppm."
  • The complaint does not explicitly reserve the right to assert dependent claims, but the general allegation of infringing "one or more claims" leaves this possibility open (Compl. ¶35).

III. The Accused Instrumentality

Product Identification

  • Defendants’ "Proposed ANDA Product," which is a generic version of LOKELMA® (sodium zirconium cyclosilicate) for oral suspension in 5 g and 10 g packets, as described in ANDA No. 217549 (Compl. ¶1). No probative visual evidence provided in complaint.

Functionality and Market Context

  • The Proposed ANDA Product contains the active ingredient sodium zirconium cyclosilicate, a non-absorbed compound that lowers serum potassium levels by capturing potassium ions in the gastrointestinal tract (Compl. ¶21, ¶28). The ANDA filing seeks approval for a product that is bioequivalent to AstraZeneca's branded LOKELMA® product (Compl. ¶30). The complaint alleges Defendants intend to market the product for the same therapeutic use upon receiving FDA approval (Compl. ¶31, ¶32).

IV. Analysis of Infringement Allegations

The complaint alleges infringement under 35 U.S.C. § 271(e)(2), where the filing of the ANDA is the statutory act of infringement (Compl. ¶27). The infringement theory is that the product described in the ANDA, and whose use will be instructed by its proposed label, meets all the limitations of the asserted claims.

'044 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treatment of hyperkalemia comprising administering over a period of more than 5 consecutive days to a patient in need thereof... The complaint alleges Defendants' proposed product label will instruct healthcare providers to prescribe the product in a manner that constitutes treatment for hyperkalemia. The "extended use" nature of the patent aligns with chronic treatment regimens. ¶32, ¶37 col. 8:36-39
a cation exchange composition comprising a zirconium silicate of formula (I): A(p)M(x)Zr(1-x)Si(n)Ge(y)O(m)... The Proposed ANDA Product's active ingredient is identified as sodium zirconium cyclosilicate, which the complaint alleges is the composition patented by the '044 Patent. ¶28, ¶29 col. 8:40-59
wherein the composition exhibits a lead content below 0.6 ppm. The complaint alleges that the Proposed ANDA Product contains a sodium zirconium silicate "as covered by one or more of the claims of the '044 Patent," which would necessarily include the lead content limitation. ¶35 col. 8:60-61
  • Identified Points of Contention:
    • Technical Question: The central factual dispute will likely be whether the Defendants' Proposed ANDA Product actually has a lead content "below 0.6 ppm." The complaint does not provide specific factual allegations or test data to support this element, asserting only that the product is "covered by" the claims (Compl. ¶35). The actual impurity profile of the generic product will be a key subject of discovery.
    • Scope Questions: For this method-of-use claim, a key question will be whether the Defendants' proposed product label instructs or encourages administration "over a period of more than 5 consecutive days." The infringement analysis will depend on the specific language of the proposed label that Defendants submitted to the FDA.

V. Key Claim Terms for Construction

  • The Term: "lead content below 0.6 ppm"
  • Context and Importance: This limitation appears to be the primary point of novelty recited in the patent, distinguishing the invention from compositions that might be unsafe for extended use. The outcome of the infringement analysis may depend entirely on whether the accused product meets this quantitative threshold.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim language itself presents a simple, objective ceiling ("below 0.6 ppm"). A party could argue for its plain and ordinary meaning, where any composition with a measured lead content less than this value infringes, regardless of the manufacturing process.
    • Evidence for a Narrower Interpretation: A party could argue that the term's meaning is informed by the specification's detailed disclosure. The patent extensively discusses a specific manufacturing process using colloidal silica as being necessary to achieve this low lead level ('044 Patent, col. 7:1-9, Example 3). Furthermore, the patent discloses a specific analytical method (ICP-MS) for determining lead content, and a party might argue this specified method is required for claim construction or infringement analysis ('044 Patent, col. 9:16-20). The patent also describes a "most preferably" range of 0.3 to 0.45 ppm, which could be used to argue the inventors contemplated a narrower scope ('044 Patent, col. 3:58-60).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement of infringement under 35 U.S.C. § 271(b) (Compl. ¶38). The factual basis for this allegation is that Defendants "will instruct healthcare providers to use the Proposed ANDA Product in accordance with the proposed product labeling," which allegedly directs users to perform the patented method (Compl. ¶37).
  • Willful Infringement: The complaint does not use the term "willful." However, it alleges that "Defendants have or will have knowledge" that making and selling the product described in the ANDA would infringe the '044 Patent (Compl. ¶39). These allegations may form the basis for a claim of post-filing willfulness.

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

  1. A central issue will be one of evidentiary proof: Can Plaintiffs demonstrate that the Defendants' proposed generic product, as specified in its ANDA, will necessarily have a "lead content below 0.6 ppm"? The complaint lacks specific data on this point, making it a critical factual question for discovery and expert testimony.
  2. The case will also turn on a question of label-induced infringement: Does the language of the Defendants' proposed product label, which is not included in the complaint, actively instruct or encourage physicians and patients to administer the drug for "more than 5 consecutive days," thereby satisfying the key temporal limitation of the asserted method claim?