DCT

1:23-cv-00031

Amgen Inc v. MSN Laboratories Pvt Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00031, D. Del., 01/12/2023
  • Venue Allegations: Venue is alleged to be proper as to the foreign defendants because they may be sued in any judicial district, and as to the domestic defendant because it is a Delaware corporation and therefore resides in the district.
  • Core Dispute: Plaintiffs allege that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the drug Parsabiv® constitutes an act of patent infringement.
  • Technical Context: The technology concerns stable, injectable liquid pharmaceutical formulations of etelcalcetide, a peptide-based drug used to treat secondary hyperparathyroidism in patients with chronic kidney disease.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendants' submission of ANDA No. 215877 with a "Paragraph IV Certification." This certification asserts that U.S. Patent No. 11,162,500 is invalid, unenforceable, and/or will not be infringed by the proposed generic product. The filing of an ANDA with such a certification is statutorily defined as an act of infringement to create federal court jurisdiction.

Case Timeline

Date Event
2013-06-28 '500 Patent Priority Date
2017-02-07 FDA approval of Plaintiffs' Parsabiv® product
2021-04-08 Plaintiff receives MSN's First Notice Letter
2021-11-02 '500 Patent Issue Date
2022-11-30 Plaintiff receives MSN's Second Notice Letter
2023-01-12 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),” issued November 2, 2021

The Invention Explained

  • Problem Addressed: The patent addresses the challenge that therapeutic peptides like etelcalcetide (also referred to as AMG 416), especially those containing disulfide bonds, tend to have poor stability in aqueous solutions, making them difficult to formulate as ready-to-use liquid injectables (’500 Patent, col. 1:56-62). Lyophilized (freeze-dried) powder formulations, while more stable, are less convenient and introduce risks of improper reconstitution and contamination before patient administration (’500 Patent, col. 2:1-5).
  • The Patented Solution: The invention provides a stable aqueous liquid formulation of etelcalcetide by controlling specific parameters, most notably the formulation's pH. The specification describes how two primary degradation pathways—C-terminal deamidation and homodimer formation—are affected in opposite ways by pH, and identifies a specific pH range that minimizes overall degradation and maximizes stability (’500 Patent, col. 9:45-58). The figures in the patent, such as Figure 4B, graphically illustrate this stability "sweet spot" where purity is maximized at a pH between 3 and 4 after 28 days of storage (’500 Patent, Fig. 4B).
  • Technical Importance: This solution enables a commercially viable, ready-to-use liquid injectable product that can be stored for extended periods, thereby avoiding the costs, user burden, and potential safety issues associated with lyophilized drugs that require reconstitution (’500 Patent, col. 2:5-12).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent Claim 1 (’Compl. ¶39, ¶41).
  • 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.
      (’500 Patent, col. 30:19-24).
  • The complaint reserves the right to assert infringement of other claims of the '500 Patent (’Compl. ¶41).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is "MSN's Proposed ANDA Product," a generic version of Parsabiv® (etelcalcetide) injection, for which MSN seeks FDA approval via ANDA No. 215877 (Compl. ¶1).

Functionality and Market Context

  • The product is an injectable drug formulation containing etelcalcetide as the active pharmaceutical ingredient (Compl. ¶33). It is intended for the same therapeutic use as Parsabiv®: the treatment of secondary hyperparathyroidism in adult patients with chronic kidney disease on hemodialysis (Compl. ¶37).
  • The complaint alleges, on information and belief, that the product described in MSN's ANDA is an aqueous solution of etelcalcetide with physical and chemical properties that fall within the scope of the asserted patent claims (Compl. ¶33, ¶40).
  • As an ANDA product, its path to market relies on establishing bioequivalence to Plaintiffs' approved Parsabiv® product, for which the '500 Patent is listed in the FDA's "Orange Book" (Compl. ¶26, ¶34).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

'500 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
[a] pharmaceutical formulation, comprising: etelcalcetide in aqueous solution, The complaint alleges that MSN's Proposed ANDA Product is a pharmaceutical formulation comprising the active ingredient etelcalcetide in an aqueous solution. ¶33, ¶40 col. 30:19-21
wherein the formulation has a pH of 2.0 to 5.0 It is alleged on information and belief that the aqueous solution in MSN's Proposed ANDA Product has a pH that falls within the range of 2.0 to 5.0. ¶33, ¶40 col. 30:22
and wherein etelcalcetide is present at a concentration of between 0.5 mg/mL to 15 mg/mL. It is alleged on information and belief that the concentration of etelcalcetide in MSN's Proposed ANDA Product is between 0.5 mg/mL and 15 mg/mL. ¶33, ¶40 col. 30:23-24
  • Identified Points of Contention:
    • Factual Questions: The complaint's infringement allegations are made on "information and belief." The central factual dispute will be whether the specific formulation parameters (pH and concentration) detailed in MSN's confidential ANDA submission actually fall within the ranges recited in Claim 1. The outcome of the literal infringement analysis will depend on the contents of the ANDA, which will be subject to discovery.
    • Scope Questions: While the claim terms appear straightforward, MSN’s Paragraph IV certification of non-infringement and invalidity raises the possibility of a dispute over claim scope (Compl. ¶30). A potential issue is whether the claimed numerical ranges are enabled and described across their full scope in the specification, or whether they are vulnerable to an invalidity challenge based on prior art that discloses similar formulations.

V. Key Claim Terms for Construction

  • The Term: "pharmaceutical formulation"
  • Context and Importance: Practitioners may focus on this term because, while seemingly broad, its interpretation could be influenced by the patent's consistent emphasis on achieving stability. Defendants in such cases sometimes argue that a general term like this should be narrowed to include the specific properties—here, enhanced stability—that the patent touts as its inventive contribution, potentially as a strategy to avoid infringement or distinguish prior art.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: Claim 1 itself defines the formulation simply by its components (etelcalcetide, aqueous solution) and two physical parameters (pH, concentration), without any explicit requirement for a specific level of stability or particular excipients (’500 Patent, col. 30:19-24). This language may support an interpretation that covers any formulation meeting these basic criteria.
    • Evidence for a Narrower Interpretation: The patent's title, abstract, and summary of the invention all frame the invention as a "stable" liquid formulation that solves the problem of peptide instability (’500 Patent, Title; Abstract; col. 2:5-12). A party could argue that this pervasive emphasis on stability implies that the term "pharmaceutical formulation" in the claims should be construed to require the specific stability characteristics described as the invention's purpose.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement of infringement, stating that MSN's proposed product labeling will instruct healthcare providers to use the product in a manner that infringes the '500 Patent (Compl. ¶35, ¶48). The specific intent for inducement is alleged based on MSN's planned actions to market the product for the patented use upon FDA approval (Compl. ¶48).
  • Willful Infringement: The complaint alleges that MSN had knowledge of the '500 Patent at the time it submitted its ANDA, citing the patent's listing in the FDA's Orange Book for Parsabiv® (Compl. ¶47). This alleged pre-suit knowledge, combined with the act of filing the ANDA, forms the basis for a potential finding of willful infringement and a request for the case to be deemed "exceptional" for the purpose of awarding attorneys' fees (Compl. p. 12, ¶(e)).

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

  • A primary issue will be one of evidentiary proof: Do the confidential specifications for pH and concentration in MSN's ANDA No. 215877 fall within the ranges of "2.0 to 5.0" and "0.5 mg/mL to 15 mg/mL", respectively, as recited in Claim 1? The literal infringement case hinges on this factual determination.
  • A second central question will be one of patent validity: Is Claim 1, which carves out a specific set of formulation parameters, nonobvious in light of prior art related to peptide formulations? The dispute will likely focus on whether the claimed pH and concentration ranges represent an inventive discovery of a stability "sweet spot" or were merely the result of routine and predictable optimization that would have been obvious to a person of ordinary skill in the art.
  • A potential legal question is one of implicit limitation: Must the term "pharmaceutical formulation" in Claim 1 be construed to require the enhanced stability that the patent specification repeatedly identifies as the invention's key advantage? The court's answer could significantly impact both the infringement and validity analyses.