DCT

1:22-cv-00704

Eagle Pharma Inc v. Accord Healthcare Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:22-cv-00704, D. Del., 07/06/22
  • Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware because Defendants are subject to personal jurisdiction in the district, have previously consented to venue in related litigation, and confirmed via email that they would not oppose venue for this action.
  • Core Dispute: Plaintiff alleges that Defendants' submission of a New Drug Application to the FDA for a generic bendamustine hydrochloride injection constitutes an act of infringement of a patent covering long-term, stable, ready-to-use liquid formulations of the drug.
  • Technical Context: The technology concerns pharmaceutical formulations of bendamustine, a chemotherapy agent, designed to be stable in a liquid, non-aqueous solution for extended periods, thereby avoiding the clinical inconvenience and instability associated with reconstituting a lyophilized powder form of the drug.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendants’ submission of New Drug Application No. 216987 with a Paragraph IV Certification against the patent-in-suit. The complaint notes that a key claim term, "stabilizing amount of an antioxidant," was previously construed by the District of Delaware in litigation involving two related patents, a fact that may inform the parties' claim construction positions in this case.

Case Timeline

Date Event
2010-01-28 U.S. Patent No. 11,103,483 Priority Date
2021-08-31 U.S. Patent No. 11,103,483 Issue Date
2022-04-18 Accord Notifies Eagle of its NDA Submission
2022-07-06 Complaint Filing Date

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

U.S. Patent No. 11,103,483 - "Formulations of Bendamustine"

  • Issued: August 31, 2021

The Invention Explained

  • Problem Addressed: The patent addresses the chemical instability of bendamustine, an anti-cancer drug, when in liquid form, particularly aqueous solutions (Compl. ¶34; ’483 Patent, col. 2:56-59). The commercially available form was a lyophilized (freeze-dried) powder that required reconstitution before use, a process described as clinically inconvenient and posing its own instability risks (’483 Patent, col. 2:59-62).
  • The Patented Solution: The invention is a "ready to use" (RTU), non-aqueous liquid formulation of bendamustine that is stable for long-term storage (’483 Patent, Abstract). The solution uses a pharmaceutically acceptable fluid, such as polyethylene glycol (PEG), combined with a "stabilizing amount of an antioxidant" to prevent degradation of the active ingredient over extended periods, such as 15 months or more (’483 Patent, col. 2:16-20, 36-44).
  • Technical Importance: This approach provides a stable, liquid bendamustine product that eliminates the need for on-site reconstitution, potentially improving safety, convenience, and dosing accuracy in a clinical setting (’483 Patent, col. 2:18-20).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claim 8 (Compl. ¶50).
  • The essential elements of independent claim 1 are:
    • A ready to use liquid bendamustine-containing composition comprising:
    • bendamustine, or a pharmaceutically acceptable salt thereof, wherein the bendamustine concentration in the composition is from about 10 mg/mL to about 100 mg/mL;
    • polyethylene glycol; and
    • a stabilizing amount of an antioxidant;
    • the composition having less than about 5% peak area response of total impurities resulting from the degradation of the bendamustine, as determined by HPLC as a wavelength of 223 nm after at least 15 months at a temperature of from about 5° C. to about 25° C.
  • The complaint states that infringement allegations include, but are not limited to, claims 1 and 8, thereby reserving the right to assert additional claims (Compl. ¶50).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendants' proposed Bendamustine Hydrochloride Injection product, formulated at a concentration of 100 mg/4 mL (25 mg/mL) in a multi-dose vial ("Accord's NDA Product") (Compl. ¶10, ¶38). This product is the subject of New Drug Application ("NDA") No. 216987, for which Defendants seek FDA approval (Compl. ¶1).

Functionality and Market Context

  • The complaint alleges that Accord's NDA Product is a "ready to use liquid bendamustine-containing composition" intended as a "concentration for solution for infusion" (Compl. ¶44). The formulation is alleged to contain bendamustine hydrochloride as its active ingredient, polyethylene glycol, and a stabilizing amount of an antioxidant (Compl. ¶¶37, 40, 41). The product is intended to be a generic version of Plaintiff's BELRAPZO® product and is alleged to have the "same or substantially similar stability" as that recited in the claims of the ’483 Patent (Compl. ¶33). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

Claim Chart Summary

U.S. Patent No. 11,103,483 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A ready to use liquid bendamustine-containing composition comprising... Accord's NDA Product is a "ready to use liquid bendamustine-containing composition." ¶44 col. 2:16-20
bendamustine, or a pharmaceutically acceptable salt thereof, wherein the bendamustine concentration...is from about 10 mg/mL to about 100 mg/mL The active ingredient is bendamustine hydrochloride, and the proposed dosage strength is 25 mg/mL. ¶¶37-38 col. 3:15-20
polyethylene glycol Accord's NDA Product contains polyethylene glycol. ¶40 col. 3:33-35
a stabilizing amount of an antioxidant Accord's NDA Product contains an amount of an antioxidant that decreases the amount of bendamustine degradation. ¶41 col. 3:60-64
the composition having less than about 5% peak area response of total impurities...after at least 15 months at a temperature of from about 5° C. to about 25° C. Accord's NDA Product allegedly has less than about 5% total impurities under the claimed storage conditions. ¶45 col. 2:36-44

Identified Points of Contention

  • Scope Questions: The complaint's focus on the prior judicial construction of "stabilizing amount of an antioxidant" suggests a potential dispute over whether the specific type and quantity of antioxidant in Accord's product meets this limitation (Compl. ¶43). A central question may be whether Accord's formulation achieves stability through the means claimed in the patent.
  • Technical Questions: The complaint states that Accord "did not disclose the composition of Accord’s NDA Product and furnish samples, data, or other information sufficient to confirm independently the exact composition" (Compl. ¶39). This raises the evidentiary question of how Plaintiff will prove that the accused product meets each claim limitation, particularly the specific impurity levels after 15 months of storage, without access to the complete formulation and stability data.

V. Key Claim Terms for Construction

"stabilizing amount of an antioxidant"

  • Context and Importance: The inclusion of a "stabilizing amount of an antioxidant" is a core element of the claimed solution to bendamustine's instability. The complaint’s reference to a prior construction of this term in litigation involving related patents indicates its critical and potentially dispositive nature (Compl. ¶43). Practitioners may focus on this term because its scope will likely determine whether Accord's use of an antioxidant infringes.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification defines "stabilizing amount" functionally as "those amounts which increase or enhance the stability of the bendamustine" ('483 Patent, col. 3:62-64). This functional language, which was the basis of the prior broad construction cited in the complaint, could support an interpretation covering any quantity of an antioxidant that has a measurable effect on degradation (Compl. ¶43).
    • Evidence for a Narrower Interpretation: The specification also provides "suitable antioxidant concentrations" within specific numerical ranges, such as "from about 2.5 mg/mL to about 35 mg/mL" ('483 Patent, col. 4:1-3). A party could argue that these examples should guide or limit the scope of the term to amounts within or near these disclosed ranges.

"ready to use"

  • Context and Importance: This term distinguishes the invention from the prior art lyophilized powders, which required a multi-step reconstitution process. Infringement requires Accord's product to be "ready to use." The complaint alleges Accord's product is a "concentration for solution for infusion," which raises a question about the meaning of "ready to use" (Compl. ¶44).
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent repeatedly contrasts the invention with lyophilized powders, suggesting "ready to use" primarily means a liquid formulation that does not require reconstitution from a solid state ('483 Patent, col. 2:18-20, 59-62).
    • Evidence for a Narrower Interpretation: The specification states that the formulations are "advantageously ready to use or ready for further dilution" ('483 Patent, col. 2:18-20). A defendant could argue that if the product requires a mandatory dilution step before infusion, it is only "ready for further dilution" and not "ready to use" in the sense of being ready for direct administration to a patient.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges active inducement of infringement based on Accord's proposed product labeling, which will allegedly encourage, recommend, and instruct the administration of the infringing composition to treat chronic lymphocytic leukemia and non-Hodgkin lymphoma (Compl. ¶¶46, 53).

Willful Infringement

  • Willfulness is alleged based on Accord's "full knowledge of the '483 patent and/or the application leading to the '483 patent" and proceeding without a reasonable basis to believe it would not be liable for infringement (Compl. ¶56). This knowledge is predicated on the Paragraph IV certification process itself.

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

  • A core issue will be one of definitional scope: does the term "stabilizing amount of an antioxidant," as defined in the patent and construed in related litigation, read on the specific quantity and type of antioxidant used in Accord's formulation, or can Accord establish a non-infringing design-around?
  • A key evidentiary question will be one of compositional proof: given the complaint's allegation that Accord has not fully disclosed its product's composition, what will discovery reveal about the formulation's precise ingredients and long-term stability data, and will that evidence be sufficient to prove that the accused product meets every limitation of the asserted claims?