DCT

3:22-cv-07603

Ingenus Pharma LLC v. Nevakar Injectables Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:22-cv-07603, D.N.J., 12/30/2022
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Nevakar is subject to personal jurisdiction and has its principal place of business in the district, and Defendant Endo is a foreign corporation which may be sued in any judicial district.
  • Core Dispute: Plaintiffs allege that Defendants' filing of a New Drug Application (NDA) for a generic version of Plaintiffs' cyclophosphamide injection constitutes an act of patent infringement under the Hatch-Waxman Act.
  • Technical Context: The technology concerns stable, ready-to-use liquid formulations for the injectable chemotherapy drug cyclophosphamide, designed to avoid the need for on-site reconstitution of a lyophilized powder.
  • Key Procedural History: This action was filed under the provisions of the Hatch-Waxman Act within 45 days of Plaintiffs' receipt of a Paragraph IV Notice Letter from Defendants, dated November 17, 2022. The filing of the complaint triggers a statutory 30-month stay of FDA approval for Defendants' NDA. The patent-in-suit is listed in the FDA's "Approved Drug Products with Therapeutic Equivalence Evaluations" (the "Orange Book"). The complaint also notes prior litigation in the district involving the same parties.

Case Timeline

Date Event
2015-02-16 ’952 Patent Priority Date
2020-07-30 Plaintiff's NDA No. 212501 for Cyclophosphamide approved
2021-05-04 U.S. Patent No. 10,993,952 Issued
2021-11-19 Plaintiff's supplemental NDA for new dosage form approved
2022-11-17 Defendants send Paragraph IV Notice Letter to Plaintiffs
2022-12-30 Complaint Filed

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

U.S. Patent No. 10,993,952 - "Stable Ready to Use Cyclophosphamide Liquid Formulations"

The Invention Explained

  • Problem Addressed: The patent's background describes that cyclophosphamide, a chemotherapy agent, was traditionally supplied as a lyophilized (freeze-dried) powder that required reconstitution with a liquid diluent before administration. This process was an extra step for healthcare providers, and the reconstituted solutions had limited stability. Furthermore, the dry powder premixes could acquire "a glassiness and or stickiness" that resulted in "inferior solubility characteristics and decreased potency." (’952 Patent, col. 2:53-59, 2:60-64).
  • The Patented Solution: The invention provides a liquid, ready-to-use parenteral formulation of cyclophosphamide that is stable and does not require reconstitution. The solution uses a specific solvent system comprising ethanol, polyethylene glycol (PEG), and propylene glycol in particular concentrations and ratios to dissolve the cyclophosphamide and maintain its chemical stability over time, thereby limiting the formation of degradation-related impurities. (’952 Patent, Abstract; col. 3:21-38).
  • Technical Importance: The development of a stable, ready-to-use liquid formulation simplifies the administration process for a critical chemotherapy drug, potentially reducing preparation time and the risk of handling errors at the point of care. (’952 Patent, col. 2:60-64).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" of the ’952 Patent without specifying them (Compl. ¶47). Independent claim 1 is representative of the invention.
  • Independent Claim 1:
    • A stable liquid parenteral formulation of cyclophosphamide comprising:
    • i) cyclophosphamide in a concentration of about 12% to about 23% by total formulation weight;
    • ii) an ethanol content of about 70% to about 75% by total formulation 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 formulation weight;
    • v) about 3.4% to about 4.4% propylene glycol by total formulation weight; and
    • vi) a functional stability requirement where, after 7 days at 40° C./75% RH, decomposition into certain specified impurities is less than 0.5%.
  • The complaint does not explicitly reserve the right to assert dependent claims, but makes a general allegation against the patent.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the cyclophosphamide solution described in Defendants' New Drug Application (NDA) No. 217651, submitted to the FDA for approval as a generic drug (Compl. ¶35).

Functionality and Market Context

  • The product is a generic version of Plaintiffs' approved Cyclophosphamide Injection product, intended for intravenous use in treating various malignant diseases (Compl. ¶¶ 30, 39). The complaint alleges the product will be offered in concentrations of 200 mg/ml (e.g., 500 mg/2.5 ml, 1 g/5 ml) (Compl. ¶11). The complaint alleges that Defendants intend to market this product in the U.S. before the expiration of the ’952 Patent, displacing sales of Plaintiffs' product (Compl. ¶¶ 23, 38). The complaint does not provide further technical details regarding the specific formulation of the accused product.

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint alleges that the product described in Defendants' NDA No. 217651 will infringe the ’952 Patent, but does not plead specific facts matching the accused formulation to each element of any asserted claim (Compl. ¶47). The analysis below maps the elements of independent claim 1 to the complaint's general infringement theory.

’952 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A stable liquid parenteral formulation of cyclophosphamide... The product described in NDA No. 217651 is alleged to be a liquid cyclophosphamide injection for intravenous use. ¶¶11, 39 col. 8:1-2
i) cyclophosphamide in a concentration of about 12% to about 23% based on total formulation weight; The complaint does not specify the concentration by weight of cyclophosphamide in the accused product, but generally alleges that the product will infringe. ¶47 col. 8:3-5
ii) an ethanol content of about 70% to about 75% based on total formulation weight; The complaint does not contain specific allegations regarding the ethanol content of the accused product, but alleges the product as a whole will infringe. ¶47 col. 8:6-7
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 contain specific allegations regarding the presence or ratio of polyethylene glycol and propylene glycol in the accused product. ¶47 col. 8:8-11
iv) about 3.4% to about 8.8% based on total formulation weight of polyethylene glycol The complaint does not contain specific allegations regarding the weight percentage of polyethylene glycol in the accused product. ¶47 col. 8:12-14
v) about 3.4% to about 4.4% based on total formulation weight of propylene glycol The complaint does not contain specific allegations regarding the weight percentage of propylene glycol in the accused product. ¶47 col. 8:15-16
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%: a) bis(2-chloroethyl)amine hydrochloride; b) 3-(2-chloroethyl)-2-oxo-2-hydroxy-1,3,6,2-oxadiazaphosphonane; and c) ... The complaint does not provide any testing data or specific allegations that the accused product meets this functional stability limitation. ¶47 col. 8:16-24
  • Identified Points of Contention:
    • Factual Questions: The central dispute will be factual: does the specific formulation detailed in the confidential NDA No. 217651 contain the claimed components within the claimed weight percentages and ratios? The complaint does not provide this information, which will be a key subject of discovery.
    • Scope Questions: The interpretation of the term "about" will be critical. The infringement analysis for multiple limitations may depend on whether the court construes "about" narrowly (e.g., limited by the precision of the patent's examples) or more broadly.
    • Technical Questions: A key evidentiary question will be whether the Defendants' product, when tested, meets the functional stability limitation of claim 1, which requires that levels of specific named impurities remain below 0.5% after accelerated storage. This may involve competing expert analysis and laboratory testing.

V. Key Claim Terms for Construction

  • The Term: "about" (appears in claim 1, limitations i, ii, iv, and v)

  • Context and Importance: This term's construction is central to the dispute, as infringement of several limitations depends on whether the accused formulation's composition falls within the claimed numerical ranges. A broader or narrower definition could be dispositive.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent repeatedly uses "about" and "approximately" in the claims and specification, which may suggest the inventors did not intend for the ranges to be read as strict, absolute limits and that some variability is contemplated (’952 Patent, col. 8:3-16).
    • Evidence for a Narrower Interpretation: The patent provides several examples with precise quantities for each component (e.g., "3.54 g" of ethanol, "0.415 g" of PEG 400) (’952 Patent, col. 3:62-64). A party could argue that the scope of "about" should be informed by the precision of these examples and the expected variance in standard pharmaceutical manufacturing.

  • The Term: "stable" (appears in the preamble of claim 1)

  • Context and Importance: Practitioners may focus on this term because its definition could influence the overall scope of the claim. The key question is whether "stable" is wholly defined by the functional limitation in part (vi) of the claim, or if it imparts a separate, broader requirement.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: A party might argue that "stable" should be given its plain and ordinary meaning in the context of pharmaceutical formulations (e.g., implying long-term shelf stability), in addition to the specific test described in limitation (vi). The patent is titled "Stable Ready to Use..." suggesting stability is a core feature of the invention beyond a single test. (’952 Patent, Title).
    • Evidence for a Narrower Interpretation: A party will likely argue that the patentee acted as their own lexicographer by providing an explicit, objective definition of the required stability in limitation (vi). This suggests that the term "stable" in the preamble is defined and limited by the subsequent functional language, and any product meeting the test in (vi) is "stable" for the purposes of the claim. (’952 Patent, col. 8:16-24).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, Defendants will induce infringement by encouraging direct infringement with knowledge of the ’952 Patent (Compl. ¶48). It also alleges contributory infringement on the basis that Defendants' product is especially made for an infringing use and has no substantial non-infringing uses (Compl. ¶49).
  • Willful Infringement: The complaint alleges that Defendants had "actual and constructive notice" of the patent prior to filing their NDA and that their certification of non-infringement or invalidity was made "without adequate justification." This conduct is alleged to make the case "exceptional" under 35 U.S.C. § 285, entitling Plaintiffs to attorneys' fees. (Compl. ¶¶ 50-51).

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

  • A primary issue will be one of factual correspondence: does the specific formulation disclosed in Defendants' confidential NDA No. 217651 actually contain the components in the concentrations and ratios required by the asserted claims? The complaint's lack of specific factual allegations makes this the central, unresolved question to be determined through discovery.
  • The case will also turn on definitional scope: how broadly will the court construe the term "about" as it applies to the numerical ranges in the claims? The outcome of this claim construction issue could directly determine whether Defendants' formulation, if close to but not exactly matching the claimed ranges, is found to infringe.
  • Finally, a key evidentiary question will be one of functional performance: does testing of Defendants' product demonstrate that it meets the specific stability requirements of claim 1, which mandate that certain degradation impurities remain below a 0.5% threshold after accelerated storage? This will likely require a "battle of the experts" with competing laboratory data.