DCT

1:24-cv-00064

Eagle Pharma Inc v. Apotex Inc

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Key Events
Amended Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00064, D. Del., 06/12/2025
  • Venue Allegations: Venue is alleged as proper based on Defendant Apotex Corp. being a Delaware corporation and Defendant Apotex Inc. being a foreign corporation subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiff alleges that Defendant’s generic bendamustine hydrochloride injection product infringes two patents related to stable, liquid pharmaceutical formulations of the drug.
  • Technical Context: The technology concerns ready-to-use liquid formulations for the chemotherapy agent bendamustine, designed to overcome the chemical instability and clinical inconvenience associated with traditional lyophilized (powder) versions that require reconstitution.
  • Key Procedural History: The complaint notes prior patent litigation between the parties involving related patents, suggesting a history of disputes over bendamustine formulations and Defendant's awareness of Plaintiff's patent portfolio.

Case Timeline

Date Event
2010-01-28 Earliest Priority Date for ’783 and ’214 Patents
2022-12-07 FDA Approval of Apotex's New Drug Application
2023-12-19 U.S. Patent No. 11,844,783 Issues
2023-12-20 Eagle sends notice letter to Apotex regarding ’783 Patent
2024-01-16 U.S. Patent No. 11,872,214 Issues
2024-01-16 Eagle sends notice letter to Apotex regarding ’214 Patent
2025-06-12 Second Amended Complaint Filed

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

U.S. Patent No. 11,844,783 - *"Formulations of Bendamustine"*

The Invention Explained

  • Problem Addressed: The patent’s background section describes that bendamustine, a chemotherapy drug, rapidly degrades when its commercial lyophilized (powder) form is reconstituted with water for injection (’783 Patent, col. 1:49-52). This instability, measured in hours, makes the reconstitution process clinically inconvenient and creates a need for formulations with enhanced long-term stability in liquid form (’783 Patent, col. 1:61-65).
  • The Patented Solution: The invention is a long-term, storage-stable liquid formulation of bendamustine that avoids the need for reconstitution (’783 Patent, col. 2:24-27). The solution involves using a specific non-aqueous, "pharmaceutically acceptable fluid," such as polyethylene glycol (PEG) or propylene glycol (PG), combined with a "stabilizing amount of an antioxidant" like thioglycerol (’783 Patent, col. 3:1-9, col. 4:1-5). This formulation is designed to limit the formation of total impurities from degradation to less than 5% after at least 15 months of storage (’783 Patent, col. 2:41-49).
  • Technical Importance: The invention provides a "ready to use" liquid bendamustine product, which improves safety and convenience for clinicians by eliminating the time-sensitive and potentially error-prone step of reconstituting a lyophilized powder before administration (’783 Patent, col. 1:61-65).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent Claim 1 (Compl. ¶28, 57).
  • Claim 1 of the ’783 Patent is a method of treatment claim with the following essential elements:
    • A method of treating leukemia comprising providing a liquid bendamustine composition.
    • The composition contains bendamustine at a concentration of about 20 mg/mL to 60 mg/mL.
    • The composition also contains a "pharmaceutically acceptable fluid consisting of" polyethylene glycol and optionally other specified solvents like ethanol.
    • The composition further contains a "stabilizing amount of an antioxidant."
    • The composition is characterized by having less than 5% total impurities after at least 15 months of storage at 5 °C to 25 °C.
    • The method concludes with the steps of diluting the composition and intravenously administering it.

U.S. Patent No. 11,872,214 - *"Formulations of Bendamustine"*

The Invention Explained

  • Problem Addressed: The ’214 Patent addresses the same technical problem as the ’783 Patent: the rapid degradation of bendamustine in aqueous solutions, which complicates the use of traditional lyophilized powder formulations (’214 Patent, col. 1:49-52).
  • The Patented Solution: The patented solution is substantively identical to that of the ’783 Patent, providing a stable, liquid, ready-to-use bendamustine formulation using a non-aqueous fluid (like PEG) and an antioxidant to control impurity formation over long-term storage (’214 Patent, Abstract; col. 3:1-9). The key difference is that the asserted claim of the ’214 patent is a product claim directed to a sterile vial containing the formulation, rather than a method of using it.
  • Technical Importance: As with the ’783 patent, this invention offers clinicians a more stable and convenient alternative to lyophilized bendamustine, reducing preparation time and potential for degradation (’214 Patent, col. 1:61-65).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent Claim 1 (Compl. ¶33, 69).
  • Claim 1 of the ’214 Patent is a product claim with the following essential elements:
    • A sterile vial containing a liquid bendamustine composition.
    • The composition comprises about 100 mg of bendamustine at a concentration of about 25 mg/mL.
    • The composition also contains a "pharmaceutically acceptable fluid consisting of" polyethylene glycol and optionally other specified solvents.
    • The composition further contains a "stabilizing amount of antioxidant."
    • The composition is characterized by having less than 5% total impurities after at least 15 months of storage at 5 °C to 25 °C.

III. The Accused Instrumentality

Product Identification

  • Defendant’s Bendamustine Hydrochloride Injection, 100 mg/4 mL (25 mg/mL), identified in the complaint as the "Apotex NDA Product" (Compl. ¶3).

Functionality and Market Context

  • The accused product is a liquid, injectable formulation of bendamustine hydrochloride (Compl. ¶3, 40). According to its Approved Labeling cited in the complaint, the formulation contains 25 mg/mL bendamustine hydrochloride, polyethylene glycol 400, ethanol, and 5 mg/mL monothioglycerol, an antioxidant (Compl. ¶41, 42, 52, 59). The FDA approved the product with an 18-month shelf life (Compl. ¶39). The complaint alleges that Apotex markets the product as "Therapeutically Equivalent to BELRAPZO®," Plaintiff’s branded product, and obtained a therapeutic equivalence code to encourage its substitution by healthcare providers (Compl. ¶60, 61).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

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 in the composition is from about 20 mg/mL to about 60 mg/mL The Apotex NDA Product is a liquid composition containing bendamustine hydrochloride at a concentration of 25 mg/mL. ¶41, 59 col. 14:56-62
a pharmaceutically acceptable fluid consisting of polyethylene glycol and optionally one or more of propylene glycol, ethanol, benzyl alcohol and glycofurol The Apotex NDA Product's Approved Labeling states that it contains polyethylene glycol 400 and ethanol. ¶42, 59 col. 14:63-65
a stabilizing amount of an antioxidant The Apotex NDA Product contains 5 mg/mL of monothioglycerol, which the patent specification identifies as a suitable antioxidant. ¶52 col. 14:66
wherein the total impurities... is less than about 5% peak area response... after at least about 15 months at a temperature of about 5 °C to about 25 °C The complaint alleges that the FDA's approval of the product for an 18-month shelf life means it must satisfy this stability requirement. ¶39, 53 col. 15:1-6
diluting the liquid bendamustine containing composition Apotex’s Approved Labeling allegedly instructs healthcare professionals to withdraw the product from the vial and transfer it to a 500 mL infusion bag of a diluent (e.g., 0.9% Sodium Chloride Injection). ¶58 col. 15:7-8
intravenously administering the diluted composition to the human Apotex’s Approved Labeling allegedly instructs intravenous administration for the treatment of leukemia. ¶54, 58 col. 15:9-10

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 The Apotex NDA Product is marketed in a 100 mg/4 mL vial, which corresponds to 100 mg of bendamustine at a concentration of 25 mg/mL. ¶70 col. 14:4-8
a pharmaceutically acceptable fluid consisting of polyethylene glycol and optionally one or more of propylene glycol, ethanol, benzyl alcohol and glycofurol The Apotex NDA Product contains polyethylene glycol 400 and ethanol. ¶42, 70 col. 14:9-12
a stabilizing amount of antioxidant The Apotex NDA Product contains monothioglycerol, an antioxidant. ¶52, 70 col. 14:13
wherein the total impurities... is less than about 5% peak area response... after at least about 15 months at a temperature of about 5 °C to about 25 °C The complaint alleges this limitation is met by inference, as the FDA would not have approved an 18-month shelf life if the product did not meet this stability requirement. ¶39, 53 col. 14:14-19

Identified Points of Contention

  • Scope Questions: Both asserted claims require a fluid "consisting of" a specific list of components. The complaint anticipates a non-infringement defense by addressing the use of sodium hydroxide "as needed to adjust pH" of the polyethylene glycol ingredient during manufacturing (Compl. ¶43-51). This raises the question of whether a processing aid used on an ingredient, which may or may not be present in the final product, falls outside the scope of a claim using the restrictive "consisting of" transition phrase.
  • Technical Questions: The complaint alleges the accused product meets the quantitative stability limitation ("less than about 5% total impurities... after at least about 15 months") by inferring this fact from the FDA's approval of an 18-month shelf life (Compl. ¶39). This raises the evidentiary question of what direct proof exists that the accused product's impurity profile, as measured by the specific HPLC method recited in the patents, actually meets the claimed threshold.

V. Key Claim Terms for Construction

  • The Term: "pharmaceutically acceptable fluid consisting of..." (’783 Patent, Claim 1; ’214 Patent, Claim 1)

  • Context and Importance: This term is critical because "consisting of" is a closed-ended phrase in patent law, meaning the fluid cannot contain other material ingredients. The complaint alleges the potential use of sodium hydroxide as a pH adjuster for an ingredient (PEG), and whether this takes the accused product outside the claim scope will likely be a central dispute (Compl. ¶43-51). Practitioners may focus on this term because it appears to be the primary basis for a potential non-infringement argument.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: A party could argue that the term refers to the primary, functional components of the fluid and does not exclude trace amounts of processing aids that do not materially affect the fluid's properties. The complaint advances this theory by arguing that sodium hydroxide is used to render the PEG compliant with its own official monograph specification, making it part of the standardized ingredient rather than a separate component of the final fluid (Compl. ¶46, 51).
    • Evidence for a Narrower Interpretation: The plain meaning of "consisting of" is strictly limiting. A party could argue that the presence of any unlisted substance in the final fluid, regardless of its origin or concentration, places the product outside the literal scope of the claims. The patent specifications do not explicitly carve out exceptions for pH adjusters or other manufacturing aids from this limitation.

  • The Term: "a stabilizing amount of an antioxidant" (’783 Patent, Claim 1; ’214 Patent, Claim 1)

  • Context and Importance: This is a functional limitation defined by its result—stabilizing the bendamustine. The scope of this term is tied to the degree of stability required by the claims (i.e., less than 5% impurities after 15 months). The dispute will concern whether the amount of antioxidant in the accused product (5 mg/mL monothioglycerol) actually performs this function to the claimed level (Compl. ¶52).

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification defines a "stabilizing amount" simply as an amount that "increase[s] or enhance[s] the stability of the bendamustine" and provides a wide range of suitable concentrations (2.5 mg/mL to 35 mg/mL), suggesting flexibility (’783 Patent, col. 4:1-10).
    • Evidence for a Narrower Interpretation: The claims themselves tie the function to a specific, measurable outcome (less than 5% impurities over 15+ months). A party could argue that a "stabilizing amount" must be an amount sufficient to achieve that specific outcome. The patent’s examples link specific concentrations of antioxidants, including 5 mg/mL, to stability data meeting this threshold, potentially limiting the term to amounts proven to be effective to that degree (’783 Patent, col. 8:44-53, Table 4).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement of the ’783 method patent. The allegations are based on Defendant’s Approved Labeling, which allegedly instructs and encourages healthcare professionals to perform the claimed method steps of diluting the liquid composition and intravenously administering it to patients for the treatment of leukemia (Compl. ¶57-58). Marketing the product as therapeutically equivalent is also alleged as an act of inducement (Compl. ¶60-61).
  • Willful Infringement: Willfulness is alleged for both patents based on Defendant’s alleged pre-suit knowledge. The complaint asserts that Defendant was aware of Plaintiff's patent portfolio from prior litigation and, further, that Plaintiff sent notice letters to Defendant on the day of or day after each patent issued (December 20, 2023, for the ’783 Patent; January 16, 2024, for the ’214 Patent) (Compl. ¶63, 72). Regular monitoring of Plaintiff’s patent filings is also alleged (Compl. ¶63, 72).

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

  • A core issue will be one of claim scope: can the restrictive claim term "consisting of," when defining a pharmaceutical fluid, be construed to permit the presence of substances used as processing aids for an ingredient during manufacturing, or does any such presence place the final product outside the boundaries of the claim?
  • A key evidentiary question will be one of infringement proof: can the plaintiff demonstrate that the accused product meets the quantitative stability limitation required by the claims, given that the complaint's allegations rely on an inference from FDA regulatory approval rather than on direct comparative testing data?
  • A third question will be one of intent: did the defendant's alleged history of litigation with the plaintiff and its alleged monitoring of the plaintiff's patent filings, combined with the post-issuance notice letters, create a basis for willful infringement from the moment the patents issued?