DCT

5:24-cv-00095

Eagle Pharma Inc v. Accord Healthcare Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 5:24-cv-00095, E.D.N.C., 02/16/2024
  • Venue Allegations: Venue is alleged to be proper as to Defendant Accord Healthcare Inc. because it is incorporated and resides in the district, and as to the foreign defendants because they are subject to personal jurisdiction within the district.
  • Core Dispute: Plaintiff alleges that Defendants' submission of a New Drug Application to the FDA for a generic version of Plaintiff's BELRAPZO® (bendamustine hydrochloride) injection constitutes an act of infringement of two patents covering stable, liquid formulations of the drug.
  • Technical Context: The technology concerns ready-to-use liquid formulations of bendamustine, an anti-cancer drug, designed to overcome the chemical instability and clinical inconvenience associated with prior-art lyophilized (freeze-dried) versions that require reconstitution.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' notification to Plaintiff on January 4, 2024, that they had filed a New Drug Application (No. 216987) with a Paragraph IV certification, challenging the patents-in-suit, which are listed in the FDA's "Orange Book" for BELRAPZO®.

Case Timeline

Date Event
2010-01-28 Earliest Priority Date for ’783 & ’214 Patents
2023-11-29 U.S. Patent No. 11,844,783 Issues
2024-01-04 Accord Sends Paragraph IV Notice Letter to Eagle
2024-01-16 U.S. Patent No. 11,872,214 Issues
2024-02-16 Complaint Filed

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

U.S. Patent No. 11,844,783 - "Formulations of Bendamustine" (Issued Nov. 29, 2023)

The Invention Explained

  • Problem Addressed: The patent describes that bendamustine, a drug for treating cancers like leukemia, is chemically unstable and degrades rapidly when reconstituted from a lyophilized (freeze-dried) powder into a liquid for injection. This reconstitution process is also clinically inconvenient, taking 15-30 minutes. (’783 Patent, col. 1:49-65).
  • The Patented Solution: The invention is a method of treatment using a liquid, ready-to-use or ready-to-dilute bendamustine formulation that exhibits long-term storage stability. The solution pairs the bendamustine active ingredient with a specific non-aqueous fluid, such as one based on polyethylene glycol (PEG), and adds a "stabilizing amount of an antioxidant." This combination is designed to limit the formation of degradation-related impurities to less than 5% after at least 15 months of storage, thereby avoiding the problems of on-site reconstitution. (’783 Patent, Abstract; col. 3:1-7).
  • Technical Importance: This approach provides healthcare professionals with a bendamustine product that simplifies drug preparation, reduces potential administration errors, and maintains chemical stability for an extended shelf life. (’783 Patent, col. 1:63-col. 2:2).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and reserves the right to assert others (Compl. ¶45).
  • Essential Elements of Claim 1:
    • A method of treating leukemia in a human comprising:
    • providing a liquid bendamustine composition with a concentration of about 20 mg/mL to 60 mg/mL;
    • in a pharmaceutically acceptable fluid "consisting of" polyethylene glycol and optionally one or more of propylene glycol, ethanol, benzyl alcohol, and glycofurol;
    • with a "stabilizing amount of an antioxidant";
    • wherein total impurities are less than about 5% after at least 15 months at 5-25 °C;
    • diluting the composition; and
    • intravenously administering the diluted composition.

U.S. Patent No. 11,872,214 - "Formulations of Bendamustine" (Issued Jan. 16, 2024)

The Invention Explained

  • Problem Addressed: The patent addresses the same technical challenge as its parent '783 Patent: the rapid degradation of bendamustine in aqueous solutions and the clinical inconvenience of reconstituting lyophilized powders before administration. (’214 Patent, col. 1:45-65).
  • The Patented Solution: Rather than a method of use, this patent claims the drug product itself: a sterile vial that contains the stable liquid bendamustine formulation. The claimed composition specifies about 100 mg of bendamustine at a concentration of about 25 mg/mL in a non-aqueous fluid containing polyethylene glycol and an antioxidant, which achieves the same long-term stability profile as described in the ’783 Patent. (’214 Patent, Abstract; col. 2:25-27).
  • Technical Importance: The invention provides a finished drug product in its final container, offering a stable, ready-to-use format that enhances safety and efficiency in clinical settings. (’214 Patent, col. 1:63-col. 2:2).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and reserves the right to assert others (Compl. ¶53).
  • Essential Elements of Claim 1:
    • A sterile vial containing a liquid bendamustine composition comprising:
    • about 100 mg of bendamustine (or salt thereof) at a concentration of about 25 mg/mL;
    • a pharmaceutically acceptable fluid "consisting of" polyethylene glycol and optionally one or more of propylene glycol, ethanol, benzyl alcohol, and glycofurol;
    • a "stabilizing amount of antioxidant";
    • wherein total impurities are less than about 5% after at least 15 months at 5-25 °C.

III. The Accused Instrumentality

Product Identification

Defendants' proposed generic version of BELRAPZO®, identified as "Accord's NDA Product," which is a bendamustine hydrochloride injection at a concentration of 100 mg/4 mL (25 mg/mL) and the subject of New Drug Application No. 216987 (Compl. ¶1).

Functionality and Market Context

The accused product is a liquid formulation of bendamustine hydrochloride intended for intravenous administration to treat chronic lymphocytic leukemia and non-Hodgkin's lymphoma (Compl. ¶¶38, 40). The complaint alleges, on information and belief, that the product contains polyethylene glycol, an antioxidant, and has stability characteristics that are the same or substantially similar to the patented BELRAPZO® product (Compl. ¶¶36, 41-42). As a generic drug, it is intended to be a lower-cost, bioequivalent alternative to the branded product (Compl. ¶¶35-36).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

U.S. Patent No. 11,844,783 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
providing a liquid bendamustine-containing composition comprising bendamustine... wherein the bendamustine concentration... is from about 20 mg/mL to about 60 mg/mL Accord's NDA Product is a liquid composition containing bendamustine hydrochloride at a concentration of 25 mg/mL. ¶¶37-38 col. 14:3-8
a pharmaceutically acceptable fluid consisting of polyethylene glycol and optionally one or more of propylene glycol, ethanol, benzyl alcohol and glycofurol Accord's NDA Product is alleged on information and belief to contain polyethylene glycol. ¶41 col. 14:9-12
a stabilizing amount of an antioxidant Accord's NDA Product is alleged on information and belief to contain a stabilizing amount of an antioxidant. ¶41 col. 14:13
wherein the total impurities... is less than about 5% peak area response, as determined by HPLC... after at least about 15 months at a temperature of about 5 °C to about 25 °C Accord's NDA Product is alleged on information and belief to have the same or substantially similar stability as BELRAPZO®, meeting the claimed impurity level. ¶¶36, 42 col. 14:14-19
diluting the liquid bendamustine containing composition; and intravenously administering the diluted composition to the human. The proposed labeling for Accord's NDA Product will allegedly direct healthcare professionals to dilute and intravenously administer the composition to treat leukemia. ¶¶40, 47 col. 14:20-22

U.S. Patent No. 11,872,214 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A sterile vial containing a liquid bendamustine-containing composition comprising about 100 mg of bendamustine... wherein the bendamustine concentration in the composition is about 25 mg/mL Accord's NDA Product is a liquid composition in a vial containing 100 mg of bendamustine hydrochloride at a concentration of 25 mg/mL. ¶¶1, 38 col. 14:2-6
a pharmaceutically acceptable fluid consisting of polyethylene glycol and optionally one or more of propylene glycol, ethanol, benzyl alcohol and glycofurol Accord's NDA Product is alleged on information and belief to contain polyethylene glycol. ¶41 col. 14:7-10
a stabilizing amount of antioxidant Accord's NDA Product is alleged on information and belief to contain a stabilizing amount of an antioxidant. ¶41 col. 14:11
wherein the total impurities... is less than about 5% peak area response, as determined by HPLC... after at least about 15 months at a temperature of about 5 °C to about 25 °C. Accord's NDA Product is alleged on information and belief to have the same or substantially similar stability as BELRAPZO®, meeting the claimed impurity level. ¶¶36, 42 col. 14:12-17

Identified Points of Contention

Scope Questions

Both asserted claims use the restrictive transition phrase "consisting of" to define the pharmaceutically acceptable fluid. A primary question for the court will be whether the accused product's fluid contains only the recited ingredients. The complaint notes that Accord has not disclosed the full composition (Compl. ¶39), suggesting a potential dispute over whether the accused product contains unlisted excipients that would place it outside the literal scope of the claims.

Technical Questions

The allegations that the accused product meets the specific stability and impurity limitations are made "upon information and belief" (Compl. ¶¶36, 42). An evidentiary question will be what proof Plaintiff can obtain through discovery from Accord's confidential NDA data to substantiate that the accused product's formulation actually achieves less than 5% total impurities after 15 months of storage under the specified conditions.

V. Key Claim Terms for Construction

Term: "pharmaceutically acceptable fluid consisting of polyethylene glycol and optionally one or more of propylene glycol, ethanol, benzyl alcohol and glycofurol"

Context and Importance

This term appears in the independent claim of both asserted patents. The phrase "consisting of" is a term of art in patent law that closes the claim to any elements not recited. Practitioners may focus on this term because if the accused product’s fluid contains any other active excipient—even a common one—it would likely fall outside the literal scope of the claim. The complaint's admission that the full composition is unknown highlights this as a central point of future dispute (Compl. ¶39).

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: A party might argue that the term does not exclude trace impurities or manufacturing residuals that are not part of the intended formulation, a standard exception to the "consisting of" rule. The specification does not appear to provide language to broaden the term beyond this narrow exception.
  • Evidence for a Narrower Interpretation: The specification consistently describes formulations using these specific components, reinforcing the closed nature of the list. For example, the summary of the invention explicitly lists these solvents (’783 Patent, col. 2:5-8), and the examples use them in various combinations (’783 Patent, col. 6:45-50). This provides strong support for a strict, closed interpretation where the fluid can only contain the listed substances.

Term: "a stabilizing amount of an antioxidant"

Context and Importance

This functional limitation is critical because it defines a required characteristic of a key ingredient. The dispute may center on whether any amount of an antioxidant suffices, or if the amount must be sufficient to achieve the claimed stability result (i.e., <5% impurities).

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The specification provides a wide quantitative range for suitable antioxidant concentrations, "from about 2.5 mg/mL to about 35 mg/mL" (’783 Patent, col. 4:8-9), which could support an argument that any amount within this range is a "stabilizing amount."
  • Evidence for a Narrower Interpretation: The patent explicitly links this term to function, stating its purpose is to "increase or enhance the stability of the bendamustine" and that its presence "contributes, at least in part to the long term stability" (’783 Patent, col. 4:3-7). A party could argue that "stabilizing amount" must be construed as an amount proven to be effective in causing the claimed stability outcome, tying it directly to the "less than 5% impurities" limitation.

VI. Other Allegations

Indirect Infringement

The complaint alleges that Defendants will induce infringement of the ’783 method patent. This allegation is based on the assertion that the proposed labeling for the accused product will instruct healthcare professionals to perform the claimed steps of diluting and administering the formulation (Compl. ¶¶47-48, 64-65). It further alleges contributory infringement, stating the product is especially adapted for this infringing use and not suitable for substantial non-infringing use (Compl. ¶¶49, 66).

Willful Infringement

The complaint seeks a declaratory judgment that Defendants have "acted without a reasonable basis for believing that it would not be liable for infringing" the patents-in-suit (Compl. ¶¶68, 80). This allegation is based on Defendants' knowledge of the patents, evidenced by their filing of a Paragraph IV certification, and on information and belief, their knowledge of the underlying patent applications (Compl. ¶¶34, 61, 73).

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

  • A core issue will be one of compositional scope: given the restrictive "consisting of" language in the claims, the case may turn on the factual question of whether the accused generic product's non-aqueous fluid contains any excipients beyond polyethylene glycol and the short list of optional solvents recited in the patents. Resolution will depend on the precise formulation revealed in discovery.
  • A key evidentiary question will be one of proven stability: can Plaintiff substantiate its "information and belief" allegations that the accused product meets the quantitative stability requirement of having "less than about 5% total impurities" after 15 months? This will require a technical battle over the interpretation of Defendants' confidential stability data from their FDA submission.