Eagle Pharma Inc v. Apotex Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Eagle Pharmaceuticals, Inc. (Delaware)
  • Defendant: Apotex Inc. (Canada) and Apotex Corp. (Delaware)
  • Plaintiff’s Counsel: McCarter & English, LLP
• Case Identification: 1:25-cv-00074, D. Del., 01/17/2025
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Apotex Corp. is a Delaware corporation, and Defendant Apotex Inc., a foreign corporation, is subject to personal jurisdiction in the district.
• Core Dispute: Plaintiff alleges that Defendants' generic Bendamustine Hydrochloride Injection product infringes a patent related to stable, ready-to-use liquid formulations of the drug.
• Technical Context: The technology involves pharmaceutical formulations designed to improve the long-term stability of the chemotherapy drug bendamustine, thereby providing a "ready-to-use" liquid product that avoids the clinical inconvenience and potential instability of reconstituting a lyophilized powder.
• Key Procedural History: The complaint alleges that Defendants filed a New Drug Application (NDA) with the FDA, which was approved. It also notes prior patent litigation between the parties concerning related technology and alleges that Plaintiff provided Defendants with notice of the patent-in-suit on the day it issued.

Case Timeline

Date	Event
2010-01-28	Earliest Priority Date for '248 Patent
2022-12-07	FDA Approval of Apotex's NDA Product
2024-11-12	U.S. Patent No. 12,138,248 Issues
2024-11-12	Eagle sends notice letter to Apotex
2025-01-17	Complaint Filed

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

• Patent Identification: U.S. Patent No. 12,138,248, “Formulations of Bendamustine,” issued November 12, 2024. (Compl. ¶25; ’248 Patent, front page).

The Invention Explained

• Problem Addressed: The patent’s background section states that bendamustine, a widely used cancer treatment, exhibits rapid degradation upon reconstitution from its conventional lyophilized (freeze-dried) powder form into an aqueous solution. (’248 Patent, col. 1:49-54). This chemical instability makes the reconstituted drug unsuitable for long-term storage and creates clinical inconvenience. (’248 Patent, col. 1:63-65).
• The Patented Solution: The invention provides a long-term, storage-stable liquid formulation of bendamustine that is "ready to use" without reconstitution. (’248 Patent, col. 1:63-65). The solution uses a non-aqueous, pharmaceutically acceptable fluid, such as polyethylene glycol (PEG), combined with a stabilizing amount of an antioxidant to prevent the degradation of bendamustine. (’248 Patent, Abstract; col. 3:1-9). This approach is designed to maintain total impurities below a specified threshold (5%) for an extended period (at least 15 months). (’248 Patent, col. 2:42-53).
• Technical Importance: This technology creates a commercially viable, ready-to-use liquid bendamustine product, which can reduce preparation time, minimize potential dosing errors, and avoid the chemical instability associated with on-site reconstitution of lyophilized powders. (’248 Patent, col. 1:63-65).

Key Claims at a Glance

• The complaint asserts infringement of at least independent claim 1. (Compl. ¶¶ 26, 49).
• Independent Claim 1 requires:
  • A sterile container containing a liquid bendamustine-containing composition.
  • The bendamustine concentration is about 25 mg/mL.
  • The composition includes a pharmaceutically acceptable fluid "consisting of" polyethylene glycol and optionally one or more of propylene glycol, ethanol, benzyl alcohol, and glycofurol.
  • The composition includes a stabilizing amount of an antioxidant.
  • The total impurities from degradation are less than about 5% peak area response via HPLC after at least 15 months of storage at a temperature from 5°C to 25°C.

III. The Accused Instrumentality

Product Identification

• The accused product is Defendants’ "Apotex NDA Product," identified as Bendamustine Hydrochloride Injection, 100 mg/4 mL (25 mg/mL). (Compl. ¶¶ 2-3).

Functionality and Market Context

• The complaint alleges the accused product is a generic version of Plaintiff’s BELRAPZO® product and is marketed as "Therapeutically Equivalent to BELRAPZO®". (Compl. ¶¶ 31, 51). The product is a sterile, injectable liquid formulation approved for treating certain types of leukemia and lymphoma. (Compl. ¶¶ 23, 50). Its Approved Labeling allegedly states it is supplied in a "multiple-dose clear glass vial" and contains bendamustine hydrochloride, polyethylene glycol 400, ethanol, and monothioglycerol. (Compl. ¶¶ 33-35, 50).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

'248 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A sterile container containing a liquid bendamustine-containing composition comprising bendamustine, or a pharmaceutically acceptable salt thereof, wherein the bendamustine concentration in the composition is about 25 mg/ml;	The accused product is described in its Approved Labeling as a sterile solution in a vial, containing bendamustine hydrochloride at a dosage strength of 25 mg/mL.	¶¶ 33, 34, 50	col. 3:24-30
a pharmaceutically acceptable fluid consisting of polyethylene glycol and optionally one or more of propylene glycol, ethanol, benzyl alcohol and glycofurol;	The product’s Approved Labeling allegedly states it contains polyethylene glycol (PEG) and ethanol. The complaint argues that the use of sodium hydroxide to adjust the pH of the PEG during manufacturing does not remove the final product from the scope of this limitation.	¶¶ 35, 38, 50	col. 3:40-54
a stabilizing amount of an antioxidant,	The product’s Approved Labeling states it contains 5 mg/mL of monothioglycerol. The patent specification identifies monothioglycerol as a suitable antioxidant and 5 mg/mL as a stabilizing amount.	¶45	col. 4:19-25
wherein the total impurities resulting from the degradation of the bendamustine is less than about 5% peak area response, as determined by HPLC at a wavelength of 223 nm 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 accused product for an 18-month shelf life implies that it meets this stability requirement. It further alleges that in a notice letter for a related patent, Defendants did not contest that their product met an identical limitation.	¶¶ 32, 46	col. 2:42-53

• Identified Points of Contention:
  • Scope Questions: The complaint dedicates significant attention to the use of sodium hydroxide in the manufacturing of the PEG component, arguing it is a processing aid that is consumed and not present in the final product. (Compl. ¶¶ 36-44). This suggests a potential dispute over the claim term "consisting of." The question for the court may be whether the use of a processing aid not listed in the claim takes the accused product outside the scope of a fluid "consisting of" the recited components.
  • Technical Questions: The complaint’s allegation that the accused product meets the "less than about 5% impurities" limitation is based on inference drawn from the FDA's approval of an 18-month shelf life. (Compl. ¶32). A central question will be what direct evidence, such as stability testing data, shows that the accused product actually meets this specific quantitative limitation under the conditions recited in the claim.

V. Key Claim Terms for Construction

• The Term: "consisting of"

• Context and Importance: This term is critical because the complaint alleges that a substance not listed in the claim—sodium hydroxide—is used to adjust the pH of the polyethylene glycol precursor during manufacturing. (Compl. ¶¶ 36-42). In patent law, "consisting of" is a closed term that presumptively excludes any unrecited elements. Practitioners may focus on this term because Defendants could argue that the manufacturing process introduces other substances or reaction byproducts, meaning the final fluid does not "consist of" only the listed ingredients.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: Plaintiff may argue that the term applies to the final composition placed in the sterile container, not to the entire manufacturing history of each precursor component. The complaint alleges that the sodium hydroxide is a pH adjuster that is "consumed in that reaction" and not present in the final product vials. (Compl. ¶42). The patent's focus on the stability of the final formulation could support an interpretation that a consumed processing aid does not negate this element. (’248 Patent, col. 3:1-9).
  • Evidence for a Narrower Interpretation: Defendants may argue for a strict interpretation, where the addition of any unlisted substance to a component, even if it reacts, violates the "consisting of" limitation. The claim language itself does not mention or contemplate the use of pH adjusters for its components. (’248 Patent, Claim 1).

• The Term: "about" (as in "about 25 mg/ml" and "less than about 5%")

• Context and Importance: The term "about" modifies the key quantitative limitations of the claim. While the concentration may be less contentious as the accused product is allegedly 25 mg/mL (Compl. ¶34), the interpretation of "about 5%" will define the threshold for infringement regarding product stability. Practitioners may focus on this term because it creates a potential gray area that will be critical for determining whether the measured impurity levels of the accused product infringe.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The patent specification uses "about" frequently when describing ranges, such as for bendamustine concentration ("from about 10 mg/mL to about 100 mg/mL") and antioxidant concentration ("from about 2.5 mg/mL to about 35 mg/mL"). (’248 Patent, col. 3:25-26; col. 4:8-9). This pattern suggests the patentee did not intend for strict numerical precision.
  • Evidence for a Narrower Interpretation: A court could look to the specific data presented in the patent’s examples to give meaning to "about." For instance, the stability data in Tables 1-8 show impurity levels measured to two decimal places, which could be used to argue for a narrower range of equivalents around the claimed "5%" value. (’248 Patent, col. 11-14).

VI. Other Allegations

• Indirect Infringement: The complaint alleges inducement of infringement based on Defendants’ affirmative acts to encourage infringing use. These acts allegedly include marketing the product as "Therapeutically Equivalent to BELRAPZO®," obtaining a therapeutic equivalence code to encourage substitution by healthcare providers, and distributing the product’s Approved Labeling, which instructs on its use. (Compl. ¶¶ 51-52).
• Willful Infringement: Willfulness is alleged based on both pre- and post-suit knowledge. The complaint asserts that Defendants were aware of Plaintiff’s patent portfolio from prior litigation and monitored Plaintiff's patent filings. (Compl. ¶54). More specifically, it alleges that Plaintiff sent Defendants a letter on November 12, 2024—the day the ’248 patent issued—notifying them of the patent and their alleged infringement, and that Defendants’ infringing conduct has continued since receiving this notice. (Compl. ¶54).

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

• A central issue will be one of claim construction: does the term "pharmaceutically acceptable fluid consisting of..." permit a manufacturing process where a precursor component is treated with a pH adjuster that is allegedly not present in the final formulation? The resolution of this question could determine whether the accused product falls within the literal scope of the patent.
• The case will also turn on a key evidentiary question: does direct evidence from stability testing confirm that Defendants' product meets the quantitative limitation of "less than about 5% total impurities" after at least 15 months, as required by Claim 1? Infringement of this limitation will likely require more than the inferential evidence presented in the complaint.