DCT

1:22-cv-00037

KAI Pharma Inc v. AuroMedics Pharma LLC

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:22-cv-00037, D. Del., 01/10/2022
  • Venue Allegations: Venue for the domestic defendants is based on their incorporation in Delaware. Venue for the foreign defendants is asserted under 28 U.S.C. § 1391(c), which permits suit against a foreign entity in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendants' filing of Abbreviated New Drug Applications (ANDAs) seeking to market generic versions of Parsabiv® (etelcalcetide) constitutes an act of infringement of a patent covering a stable liquid formulation of the drug.
  • Technical Context: The technology relates to pharmaceutical formulations for peptide-based drugs, specifically creating a stable, ready-to-use aqueous solution to avoid the cost and inconvenience of products that require reconstitution before use.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 215840 (Aurobindo) and ANDA No. 215877 (MSN) to the U.S. Food and Drug Administration. The patent-in-suit is subject to a terminal disclaimer.

Case Timeline

Date Event
2013-06-28 '500 Patent Priority Date
2017-02-07 FDA grants approval for Parsabiv® (etelcalcetide)
2021-03-26 Plaintiff receives Aurobindo's ANDA Notice Letter
2021-04-08 Plaintiff receives MSN's ANDA Notice Letter
2021-11-02 '500 Patent Issue Date
2022-01-10 Complaint Filing Date

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

U.S. Patent No. 11,162,500 - "Stable Liquid Formulation of AMG 416 (Etelcalcetide)"

  • Patent Identification: U.S. Patent No. 11,162,500, "Stable Liquid Formulation of AMG 416 (Etelcalcetide)," issued November 2, 2021.

The Invention Explained

  • Problem Addressed: The patent describes that therapeutic peptides like etelcalcetide (identified as AMG 416), particularly those with disulfide bonds, often have poor stability in aqueous solutions. This instability can necessitate providing the drug in a lyophilized (freeze-dried) powder form, which must be reconstituted before use. This process is described as less convenient, more costly, and introduces risks of improper dilution or contamination (’500 Patent, col. 1:55 - col. 2:5).
  • The Patented Solution: The invention provides a stable, aqueous liquid formulation of etelcalcetide that is suitable for parenteral administration. The key to the solution is maintaining the formulation's pH within a specific range, which is disclosed to balance two competing chemical degradation pathways: C-terminal deamidation, which predominates at lower pH, and homodimer formation, which predominates at higher pH (’500 Patent, col. 2:16-23; col. 9:45-59). By controlling the pH, the formulation can remain stable over an extended period, creating a ready-to-use product (’500 Patent, col. 2:6-12).
  • Technical Importance: Developing a stable, liquid, ready-to-use formulation simplifies drug administration and enhances patient safety by eliminating the need for reconstitution, a significant advantage in the clinical setting for intravenous drugs (’500 Patent, col. 2:6-12).

Key Claims at a Glance

  • The complaint asserts infringement of independent claim 1 (Compl. ¶66, ¶79).
  • The essential elements of independent claim 1 are:
    • A pharmaceutical formulation comprising etelcalcetide in aqueous solution,
    • wherein the formulation has a pH of 2.0 to 5.0 and
    • wherein etelcalcetide is present at a concentration of between 0.5 mg/mL to 15 mg/mL.
  • The complaint alleges infringement of "one or more claims," preserving the right to assert additional claims, including dependent claims (Compl. ¶67, ¶80).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are the proposed generic etelcalcetide injection products described in Aurobindo's ANDA No. 215840 and MSN's ANDA No. 215877 (Compl. ¶1).

Functionality and Market Context

  • The accused products are intended to be generic versions of Plaintiffs' branded drug, Parsabiv®, for the treatment of secondary hyperparathyroidism in adult patients with chronic kidney disease on hemodialysis (Compl. ¶2, ¶3).
  • The complaint alleges, upon information and belief, that both proposed generic products are "a pharmaceutical formulation comprising etelcalcetide in an aqueous solution having a pH of 2.0 to 5.0 and an etelcalcetide concentration of between 0.5 mg/mL to 15 mg/mL" (Compl. ¶56, ¶60). These alleged characteristics directly map onto the limitations of asserted claim 1 of the ’500 Patent.
  • Upon FDA approval, these products would be marketed as direct competitors to Parsabiv® (Compl. ¶2, ¶3).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

  • Claim Chart Summary: The complaint alleges that both the Aurobindo and MSN proposed ANDA products will infringe the ’500 Patent. The infringement theory is identical for both sets of defendants and is based on the alleged properties of their respective generic formulations.
Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical formulation comprising etelcalcetide in aqueous solution, The proposed ANDA product is alleged to be a pharmaceutical formulation containing etelcalcetide in an aqueous solution. ¶56, ¶60 col. 2:16-18
wherein the formulation has a pH of 2.0 to 5.0 and The proposed ANDA product is alleged to have a pH between 2.0 and 5.0. ¶56, ¶60 col. 2:18-20
wherein etelcalcetide is present at a concentration of between 0.5 mg/mL to 15 mg/mL. The proposed ANDA product is alleged to have an etelcalcetide concentration between 0.5 mg/mL and 15 mg/mL. ¶56, ¶60 col. 9:18-20
  • Identified Points of Contention:
    • Factual Questions: The complaint's infringement allegations are made "on information and belief" (Compl. ¶56, ¶60). A central point of contention will therefore be factual: whether discovery confirms that the specifications for pH and concentration in the Defendants' confidential ANDA filings fall within the ranges recited in claim 1.
    • Scope Questions: The infringement theory presented is one of literal infringement, where the accused products are alleged to meet every claim limitation exactly. This suggests that if the complaint's factual assertions are correct, the primary dispute may shift from non-infringement to the validity of the ’500 patent's claims.

V. Key Claim Terms for Construction

  • The Term: "a pH of 2.0 to 5.0"
  • Context and Importance: This pH range is the central feature of the claimed invention, defining the purported "sweet spot" of maximum stability. Practitioners may focus on this term because its precise meaning—whether it requires the pH to remain strictly within this range for the product's entire shelf life or refers to a target range at the time of manufacture—could determine the outcome of the infringement analysis.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification frequently uses the word "about" when discussing the claimed pH range, stating "the formulation has a pH of about 2.0 to about 5.0" (’500 Patent, col. 2:18-20) and that it "typically has a pH of about 2.0 to about 5.0" (’500 Patent, col. 9:36-37). A party could argue this language supports a construction that allows for minor deviations from the recited 2.0-5.0 endpoints.
    • Evidence for a Narrower Interpretation: The claim itself recites "a pH of 2.0 to 5.0" without the modifier "about." A party could argue that the patentees deliberately chose to claim the range precisely, effectively disclaiming any scope beyond the recited numerical boundaries. The presentation of stability data at distinct pH integers (e.g., pH 2, 3, 4, 5) could also be used to argue that the inventors viewed these as defining a precise, rather than approximate, operational range (’500 Patent, Fig. 3A-3B).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendants will actively induce infringement upon approval of their ANDAs (Compl. ¶73, ¶86). The basis for this allegation is that the proposed product labels will instruct healthcare providers and other users to administer the generic products in a manner that directly infringes one or more claims of the ’500 patent (Compl. ¶58, ¶62, ¶68).
  • Willful Infringement: While not pleaded as a separate count, the complaint lays the groundwork for a finding of willfulness by alleging that Defendants have "no reasonable basis to believe" that their proposed products would not infringe the ’500 patent (Compl. ¶69, ¶82). The complaint was filed after the patent issued, establishing Defendants' post-suit knowledge.

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

  • A primary issue will be one of evidentiary confirmation: will discovery into the contents of Defendants' confidential ANDA filings substantiate the complaint's allegations that the proposed generic products are formulated with a pH and drug concentration that fall literally within the scope of claim 1 of the ’500 patent?
  • A second central question, likely contingent on the first, will concern patent validity: assuming the accused products are found to infringe, was it obvious to a person of ordinary skill in pharmaceutical formulation in 2013 to create a stable aqueous solution of etelcalcetide by maintaining the pH between 2.0 and 5.0, in light of prior art knowledge regarding peptide chemistry and pH-based stability optimization?