DCT
1:23-cv-01187
ZS Pharma Inc v. Alkem Laboratories Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: ZS Pharma, Inc. (Delaware) and AstraZeneca Pharmaceuticals LP (Delaware)
- Defendant: Alkem Laboratories Ltd. (Republic of India)
- Plaintiff’s Counsel: McCarter & English, LLP; O'Melveny & Myers LLP
- Case Identification: 1:23-cv-01187, D. Del., 10/20/2023
- Venue Allegations: Venue is alleged to be proper because Defendant is a foreign corporation subject to personal jurisdiction in the district.
- Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the drug LOKELMA® constitutes an act of infringement of a patent covering low-lead zirconium silicate compositions and methods of their use.
- Technical Context: The technology concerns pharmaceutical compositions for treating hyperkalemia (dangerously high potassium levels in the blood), a condition often associated with kidney disease and heart failure.
- Key Procedural History: This action arises from Defendant's filing of ANDA No. 217558, which included a Paragraph IV Certification for the patent-in-suit, asserting that the patent is invalid, unenforceable, or will not be infringed. The complaint notes that the same ANDA was the subject of a previous lawsuit filed by Plaintiffs against Defendant on August 22, 2022, involving different patents.
Case Timeline
| Date | Event |
|---|---|
| 2015-10-14 | Earliest Priority Date for '044 Patent |
| 2022-07-14 | Date of Defendant's Notice Letter regarding ANDA No. 217558 |
| 2022-08-22 | Plaintiffs filed prior suit regarding ANDA No. 217558 |
| 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
- Patent Identification: 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 serious health risks of hyperkalemia and notes that existing treatments can have significant side effects, such as intestinal obstruction, or are otherwise unsuitable for long-term administration (’044 Patent, col. 2:23-52). Furthermore, the patent explains that manufacturing zirconium silicate compositions at an industrial scale can introduce impurities, particularly lead, to levels that are unacceptable for extended pharmaceutical use (’044 Patent, col. 3:15-34).
- The Patented Solution: The invention is a zirconium silicate composition specifically formulated for extended use in treating hyperkalemia, characterized by a very low lead content of less than 0.6 parts per million (ppm) (’044 Patent, col. 3:56-61). The patent also details a manufacturing process, using colloidal silica and specific reaction conditions in a large-scale reactor, designed to achieve this high level of purity while maintaining the material's effectiveness at binding potassium (’044 Patent, col. 7:1-9; col. 11:38-51).
- Technical Importance: By achieving a significantly lower lead content, the invention purports to create a zirconium silicate composition that is safe for the long-term, chronic administration required to manage persistent hyperkalemia, addressing a limitation of prior compositions (’044 Patent, col. 1:19-23).
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims" without specifying which ones (Compl. ¶27). Independent claim 1 is a representative method of treatment claim.
- Independent Claim 1:
- A method of treatment of hyperkalemia
- comprising administering over a period of more than 5 consecutive days to a patient in need thereof
- a cation exchange composition comprising a zirconium silicate of formula (I)
- wherein 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. ¶27).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is Defendant's "Proposed ANDA Product," a generic version of LOKELMA® (sodium zirconium cyclosilicate) for oral suspension, intended to be marketed in 5 g and 10 g per packet dosages (Compl. ¶1).
Functionality and Market Context
- The Proposed ANDA Product is a pharmaceutical intended to treat hyperkalemia by acting as a non-absorbed zirconium silicate that captures potassium in the gastrointestinal tract in exchange for hydrogen and sodium, thereby lowering serum potassium levels (Compl. ¶14). The complaint alleges that Defendant's ANDA filing relies on data demonstrating the bioequivalence of its Proposed ANDA Product to Plaintiffs' LOKELMA® product (Compl. ¶22). The infringement alleged is the statutory act of filing the ANDA to seek approval for this product before the expiration of the ’044 Patent (Compl. ¶1, ¶19). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint alleges that the filing of ANDA No. 217558 constitutes infringement under 35 U.S.C. § 271(e)(2) and that future commercialization will constitute direct and indirect infringement (Compl. ¶19, ¶30). The infringement theory for the method claims appears to rely on the allegation that the proposed product label will instruct healthcare providers and patients to use the product in a manner that performs the claimed method steps (Compl. ¶23-24, ¶29).
’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... to a patient in need thereof | Defendant's Proposed ANDA Product is intended for use by healthcare providers to treat hyperkalemia, as will be set forth in its proposed product label. | ¶23, ¶24 | col. 13:35-38 |
| over a period of more than 5 consecutive days | The complaint does not specify facts related to this duration but alleges the proposed label will instruct infringing use. | ¶24, ¶29 | col. 13:36-37 |
| a cation exchange composition comprising a zirconium silicate of formula (I) | The Proposed ANDA Product's active ingredient is sodium zirconium cyclosilicate, which the complaint alleges is "as patented by the '044 Patent." | ¶20, ¶21, ¶27 | col. 11:38-40 |
| wherein the composition exhibits a lead content below 0.6 ppm | The complaint alleges that the Proposed ANDA Product infringes claims of the patent, which requires inferring that it meets this limitation. No specific data on the product's lead content is provided. | ¶21, ¶27 | col. 13:60-62 |
- Identified Points of Contention:
- Technical Question: A central factual dispute will likely be whether Defendant's Proposed ANDA Product, as it would be commercially manufactured, actually "exhibits a lead content below 0.6 ppm" as required by claim 1. The complaint does not provide evidence on this point, which will be a focus of discovery.
- Scope Question: The analysis may raise the question of whether Defendant's proposed product label will instruct administration "over a period of more than 5 consecutive days." Infringement of this method step will depend on the specific language of the instructions for use that Defendant submits to the FDA.
V. Key Claim Terms for Construction
The Term: "lead content below 0.6 ppm"
Context and Importance: This limitation is the core of the patent's asserted novelty over prior art compositions that may have been unsuitable for long-term use. Proving that the accused product meets this negative limitation is essential to the Plaintiff's infringement case. Practitioners may focus on this term because the method of measurement could influence the outcome of whether the limitation is met.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The plain language of the claim suggests any amount less than 0.6 ppm, without specifying a lower bound other than zero.
- Evidence for a Narrower Interpretation: The patent specification repeatedly frames the invention in the context of specific ranges, such as "from 0.1 and 0.6 ppm, more preferably from 0.3 to 0.5 ppm" (’044 Patent, col. 3:56-59). Claim 13 explicitly requires that the lead content is "determined using inductively coupled plasma-mass spectrometry (ICP-MS)," suggesting that the claim term must be interpreted in light of the specific measurement protocol described in the patent (’044 Patent, col. 6:5-13, col. 14:12-15).
The Term: "administering over a period of more than 5 consecutive days"
Context and Importance: This term connects the method to the patent's "extended use" purpose. Its construction will be critical for determining whether the instructions on the accused product's label induce infringement of the method claim.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party might argue this term is met by any administration period that exceeds five full 24-hour periods in a row.
- Evidence for a Narrower Interpretation: The specification's focus on "long term administration" and "chronic basis" use to "prevent the relapse or occurrence" of hyperkalemia could suggest a more prolonged or continuous period of administration is contemplated, beyond just six days (’044 Patent, col. 1:19-23; col. 2:49-52).
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b), stating that Defendant intends for healthcare providers to use the Proposed ANDA Product as instructed by the product label, which will allegedly direct use in an infringing manner (Compl. ¶29, ¶30). The complaint also alleges contributory infringement under § 271(c), asserting that the product is not a staple article of commerce and is especially made or adapted for an infringing use (Compl. ¶31).
- Willful Infringement: The complaint alleges that Defendant has or will have knowledge of the ’044 Patent and of its infringement (Compl. ¶31). The basis for this knowledge includes Defendant's amendment of its ANDA to include a Paragraph IV Certification against the ’044 Patent (Compl. ¶18). While not using the word "willful," the complaint requests a declaration that the case is "exceptional" and an award of attorneys' fees under 35 U.S.C. § 285 (Prayer for Relief ¶(e)).
VII. Analyst’s Conclusion: Key Questions for the Case
The resolution of this case appears to hinge on two primary questions for the court:
- A core issue will be one of evidentiary proof: Can Plaintiffs demonstrate through discovery and testing that Defendant’s Proposed ANDA Product, as manufactured at a commercial scale, will in fact contain a "lead content below 0.6 ppm," thereby meeting the central limitation of the asserted claims?
- A key infringement question will be one of label-based instruction: Does the specific language of the proposed label for Defendant's generic product instruct or encourage physicians and patients to administer the drug "over a period of more than 5 consecutive days," thereby satisfying the "extended use" limitation of the asserted method claim?