DCT

1:23-cv-00377

Ingenus Pharma LLC v. Accord Healthcare Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00377, D. Del., 04/03/2023
  • Venue Allegations: Plaintiffs allege venue is proper based on Defendant's business activities in Delaware, purposeful availment of the forum through prior litigation, and express consent to venue provided by Defendant's counsel.
  • Core Dispute: This is a Hatch-Waxman Act case in which Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic cyclophosphamide solution constitutes an act of infringement of a patent covering a stable, ready-to-use liquid formulation of the drug.
  • Technical Context: The technology concerns pharmaceutical formulations for cyclophosphamide, an injectable chemotherapy agent, designed to be stable in a liquid, ready-to-use form to avoid the need for reconstitution before administration.
  • Key Procedural History: The lawsuit was triggered by Defendant's "Notice Letter," which included a Paragraph IV certification asserting that its proposed generic product would not infringe or that the patent-in-suit is invalid. The complaint was filed within the 45-day statutory window, which triggers an automatic 30-month stay of FDA approval for Defendant's ANDA.

Case Timeline

Date Event
2015-02-16 '952 Patent Priority Date
2020-07-30 Plaintiff's New Drug Application (NDA) No. 212501 approved
2021-05-04 U.S. Patent No. 10,993,952 Issued
2021-11-19 Plaintiff's supplemental NDA approved
2023-02-20 Defendant sends Paragraph IV Notice Letter to Plaintiffs
2023-04-03 Complaint Filed

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

U.S. Patent No. 10,993,952 - "Stable Ready to Use Cyclophosphamide Liquid Formulations" (Issued May 4, 2021)

The Invention Explained

  • Problem Addressed: The patent's background explains that cyclophosphamide is susceptible to hydrolysis, or degradation in the presence of water. (’952 Patent, col. 2:37-38). Consequently, prior formulations were typically supplied as lyophilized (freeze-dried) powders that required reconstitution with a liquid before use, a process that is inconvenient and can lead to handling errors. (’952 Patent, col. 1:60-64).
  • The Patented Solution: The invention is a liquid, ready-to-use parenteral formulation that is stable without lyophilization. This is achieved by dissolving cyclophosphamide in a specific, non-aqueous solvent system that includes ethanol, polyethylene glycol (PEG), and propylene glycol in particular concentrations and ratios, optionally with an antioxidant. (’952 Patent, Abstract; col. 3:26-30, 51-59).
  • Technical Importance: By creating a stable liquid formulation, the invention eliminates the need for on-site reconstitution by healthcare professionals, thereby simplifying the administration process and reducing the potential for error. (’952 Patent, col. 1:60-64).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" of the '952 Patent (Compl. ¶36). The patent contains two independent claims, 1 and 4.
  • Independent Claim 1 recites the essential elements of the formulation:
    • A stable liquid parenteral formulation of cyclophosphamide comprising:
    • i) cyclophosphamide in a concentration of about 12% to about 23% by total weight;
    • ii) an ethanol content of about 70% to about 75% by total weight;
    • iii) both polyethylene glycol and propylene glycol, with a PEG-to-propylene glycol mass ratio between approximately 1.0:1.0 and 2.0:1.0;
    • iv) about 3.4% to about 8.8% polyethylene glycol by total weight;
    • v) about 3.4% to about 4.4% propylene glycol by total weight; and
    • vi) a stability requirement where, after 7 days at 40° C./75% RH, decomposition into certain specified impurities is less than 0.5%.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Defendant’s proposed generic cyclophosphamide solution for intravenous injection, as described in Abbreviated New Drug Application (ANDA) No. 218250 (the "ANDA Product") (Compl. ¶1). The ANDA seeks approval for concentrations of 500mg/2.5ml, 1gm/5ml, and 2gm/10ml, all corresponding to 200mg/ml (Compl. ¶10).

Functionality and Market Context

The ANDA Product is an injectable solution intended for the treatment of various malignant diseases (Compl. ¶20, 29). The complaint alleges that the ANDA Product is a purported generic version of Plaintiffs' approved NDA Product and, if approved, will be sold in the U.S. to compete with and displace sales of Plaintiffs' product (Compl. ¶¶14, 25).

IV. Analysis of Infringement Allegations

The complaint alleges that Defendant’s ANDA Product "falls within one or more claims of the '952 Patent" but does not provide a detailed, element-by-element infringement analysis or an appended claim chart (Compl. ¶36). The infringement theory is based on the contents of Defendant's confidential ANDA submission.

No probative visual evidence provided in complaint.

'952 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
i) cyclophosphamide in a concentration of about 12% to about 23% based on total formulation weight; The complaint alleges the ANDA Product is a cyclophosphamide solution at a concentration of 200 mg/mL, intended as a generic version of Plaintiffs' product. ¶1, ¶10 col. 7:22-24
ii) an ethanol content of about 70% to about 75% based on total formulation weight; The complaint does not specify the ethanol content of the ANDA Product but makes a general allegation that the product infringes one or more claims. ¶36 col. 7:25-26
iii) both polyethylene glycol and propylene glycol, wherein a polyethylene glycol to propylene glycol mass ratio is between approximately 1.0:1.0 to approximately 2.0:1.0; The complaint does not specify the excipients or their ratios in the ANDA Product but alleges the product meets the limitations of the asserted claims. ¶36 col. 8:1-3
iv) about 3.4% to about 8.8% based on total formulation weight of polyethylene glycol The complaint does not specify the polyethylene glycol content of the ANDA Product but alleges the product infringes. ¶36 col. 8:27-29
v) about 3.4% to about 4.4% based on total formulation weight of propylene glycol The complaint does not specify the propylene glycol content of the ANDA Product but alleges the product infringes. ¶36 col. 8:1-2
vi) wherein, after storage for 7 days at 40° C./75% RH, decomposition to form any of the following impurities is less than 0.5%... The complaint does not provide stability data for the ANDA Product but alleges it will infringe upon commercialization. ¶39 col. 8:4-12

Identified Points of Contention

  • Factual Questions: The central dispute will be factual: does the formulation described in Defendant's confidential ANDA contain the claimed ingredients in the claimed concentrations and ratios? Because the complaint lacks specific factual allegations mapping the ANDA formulation to the claim elements, this determination will depend entirely on discovery.
  • Scope Questions: The interpretation of the term "about," used to qualify every concentration range in Claim 1, will be a critical issue. The scope afforded to "about" could determine whether Defendant's formulation literally infringes, particularly if its component percentages are close to but not exactly matching the recited ranges.
  • Technical Questions: A key technical question is whether the ANDA Product meets the functional limitation of Claim 1(vi) regarding stability and impurity levels under specified conditions. This will likely require laboratory testing of the proposed generic product.

V. Key Claim Terms for Construction

The complaint does not provide sufficient detail for a full analysis of claim construction disputes. However, based on the claim language, certain terms are likely to be central.

  • Term: "about"

    • Context and Importance: This term qualifies all five compositional limitations in Claim 1. Its construction will directly impact the scope of the claims and will be critical for determining literal infringement, as the Defendant’s formulation may have concentrations that are near, but not identical to, the recited numerical endpoints.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: Plaintiffs may argue that the specification’s disclosure of much wider "preferred" ranges (e.g., "5-40%" for cyclophosphamide and "20-98%" for ethanol) suggests the inventors did not intend the claims to be strictly limited to the recited values (’952 Patent, col. 3:51-59).
      • Evidence for a Narrower Interpretation: Defendant may argue that the claims recite specific, "optimised" ranges necessary to achieve the desired stability (’952 Patent, col. 2:19-22). They may contend that "about" should only encompass minor variations inherent in measurement, as the specific ranges were what distinguished the invention.

  • Term: "stable"

    • Context and Importance: This term appears in the preamble of Claim 1 ("A stable liquid parenteral formulation..."). Practitioners may focus on this term because its interpretation could either add a separate requirement for infringement or be rendered superfluous by the more specific stability limitation recited in the body of the claim.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation (Non-limiting): A plaintiff would likely argue that the preamble states an intended purpose and that the patentee defined the operative meaning of "stable" within the body of the claim itself—specifically, the impurity limitation in clause (vi) (’952 Patent, col. 8:4-12).
      • Evidence for a Narrower Interpretation (Limiting): A defendant could argue that "stable" is a separate, essential feature of the invention that must be met, pointing to the patent's emphasis on overcoming the instability of prior art formulations as a key objective (’952 Patent, col. 2:37-40).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, Defendant will induce infringement by, among other things, instructing users via its product labeling to use the ANDA Product in an infringing manner (Compl. ¶¶31, 40). Contributory infringement is alleged on the basis that the ANDA Product is "especially made or especially adapted for a use that infringes" and has "no substantial noninfringing uses" (Compl. ¶41).
  • Willful Infringement: Willfulness is alleged based on Defendant’s "actual and constructive notice" of the '952 Patent prior to filing its ANDA (Compl. ¶42). The complaint further alleges that Defendant's Paragraph IV certification lacked a "reasonable basis," rendering the case "exceptional" under 35 U.S.C. § 285 (Compl. ¶¶42-43).

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

  • A primary issue is one of evidentiary proof: does the chemical formulation described in Defendant's confidential ANDA actually contain the specific components, in the specific concentrations and ratios, required by the asserted claims? The outcome will hinge on discovery of the ANDA's contents.
  • A second core issue will be one of definitional scope: how broadly will the court construe the term "about" as it applies to the numerical ranges in the claims? The resolution of this claim construction question may determine whether Defendant's product literally infringes.
  • A final key question will be one of functional performance: does Defendant's proposed product meet the stability requirement of Claim 1, which limits the formation of specific impurities to less than 0.5% under accelerated storage conditions? This will likely require expert analysis and testing of the accused formulation.