DCT
1:21-cv-01256
Eagle Pharma Inc v. Slayback Pharma LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Eagle Pharmaceuticals, Inc. (Delaware)
- Defendant: Slayback Pharma LLC (Delaware); Apotex Inc. (Canada); Apotex Corp. (Delaware)
- Plaintiff’s Counsel: Shaw Keller LLP
- Case Identification: 1:21-cv-01256, D. Del., 08/31/2021
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Slayback Pharma LLC and Apotex Corp. are incorporated in Delaware. For Apotex Inc., a Canadian corporation, venue is based on it being subject to personal jurisdiction in the district.
- Core Dispute: Plaintiff alleges that Defendants' submission of New Drug Applications (NDAs) to the FDA for generic versions of Plaintiff's BELRAPZO® product constitutes an act of infringement of a patent covering stable, ready-to-use liquid formulations of bendamustine.
- Technical Context: The lawsuit concerns liquid formulations for bendamustine hydrochloride, an alkylating drug used in chemotherapy to treat certain types of leukemia and lymphoma, which is historically unstable in aqueous solutions.
- Key Procedural History: The complaint notes prior litigation between Eagle and Slayback over related patents that share the same specification as the patent-in-suit. In that litigation, Slayback reportedly conceded that its proposed product met all limitations of a representative claim except for one. The complaint also states that Slayback's NDA for its product received tentative FDA approval on July 2, 2020.
Case Timeline
| Date | Event |
|---|---|
| 2010-01-28 | '483 Patent Priority Date |
| 2018-10-31 | Slayback sends notice letter to Eagle regarding its NDA |
| 2020-07-02 | Slayback's NDA Product receives tentative FDA approval |
| 2021-08-16 | Apotex sends notice letter to Eagle regarding its NDA |
| 2021-08-31 | '483 Patent Issue Date |
| 2021-08-31 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,103,483 - "Formulations of Bendamustine"
- Patent Identification: 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 in aqueous solutions, which necessitates that it be supplied as a lyophilized (freeze-dried) powder. This powder requires a clinically inconvenient and time-consuming reconstitution process before administration, which itself can lead to degradation of the active ingredient ('483 Patent, col. 6:52-60).
- The Patented Solution: The invention provides long-term storage stable, "ready to use" (RTU) liquid formulations of bendamustine. The solution involves dissolving bendamustine in a non-aqueous, pharmaceutically acceptable fluid, such as polyethylene glycol (PEG) or propylene glycol (PG), and including a "stabilizing amount of an antioxidant" to prevent degradation over time ('483 Patent, Abstract; col. 6:61-65).
- Technical Importance: By creating a stable liquid formulation, the invention obviates the need for on-site reconstitution, which can simplify clinical workflow, reduce preparation time, and minimize the risk of product degradation before patient administration ('483 Patent, col. 6:56-60).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claim 8 (Compl. ¶¶56, 66).
- Independent Claim 1 requires:
- A ready to use liquid bendamustine-containing composition;
- Comprising bendamustine (or a salt thereof) at a concentration of about 10 mg/mL to 100 mg/mL;
- Comprising polyethylene glycol;
- Comprising a stabilizing amount of an antioxidant; and
- Having less than about 5% total impurities from degradation after at least 15 months of storage at a temperature between 5 °C and 25 °C.
- The complaint reserves the right to assert additional claims of the '483 patent (Compl. ¶¶56, 66).
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are "Slayback's NDA Product" (associated with NDA No. 212209) and "Apotex's NDA Product" (associated with NDA No. 215033) (Compl. ¶¶33, 45).
Functionality and Market Context
- The complaint alleges both accused products are ready-to-use liquid compositions of bendamustine hydrochloride at a concentration of 25 mg/mL (Compl. ¶¶39, 40, 42, 48, 49, 51).
- The formulations are alleged to contain polyethylene glycol and a stabilizing amount of an antioxidant (Compl. ¶¶41, 50).
- The products are intended for administration to patients with chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma (Compl. ¶¶44, 53). The complaint alleges that the proposed products rely on bioavailability and/or bioequivalence data from Eagle's approved BELRAPZO® product (Compl. ¶¶1, 37, 46).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
'483 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A ready to use liquid bendamustine-containing composition comprising | The accused Slayback and Apotex products are described as ready-to-use liquid bendamustine-containing compositions. | ¶42, ¶51 | col. 6:58-60 |
| 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; | The accused products are alleged to contain bendamustine hydrochloride at a proposed dosage strength of 25 mg/mL. | ¶39, ¶40, ¶48, ¶49 | col. 12:22-25 |
| polyethylene glycol; and | The accused products are alleged to contain polyethylene glycol. | ¶41, ¶50 | col. 12:26-27 |
| a stabilizing amount of an antioxidant; | The accused products are alleged to contain a stabilizing amount of an antioxidant. | ¶41, ¶50 | col. 12:27-28 |
| 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 accused products are alleged to have less than about 5% total impurities under the specified conditions, and to have stability that is the same or substantially similar to that recited in the claims. | ¶43, ¶52, ¶37, ¶46 | col. 12:29-34 |
Identified Points of Contention
- Technical Questions: A central factual dispute may concern whether the accused products actually meet the quantitative stability limitation of having "less than about 5% peak area response of total impurities" after 15 months under the specified storage conditions. The outcome will likely depend on expert analysis of stability data from the defendants' NDAs. Another question is whether the amount of antioxidant present in the accused products is, in fact, a "stabilizing amount."
- Scope Questions: The case may raise the question of whether the term "ready to use," as defined in the patent, reads on the accused products if they require any form of dilution or preparation prior to infusion. The complaint alleges they are RTU, but this could become a point of dispute.
V. Key Claim Terms for Construction
The Term: "ready to use"
- Context and Importance: This term is used to distinguish the invention from prior art lyophilized powders requiring significant reconstitution. Its construction is critical because if the accused products require any preparation that the court deems to be outside the scope of "ready to use," infringement may be avoided.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification states that "The inventive formulations are advantageously ready to use or ready for further dilution," which may suggest that the term does not foreclose a dilution step ('483 Patent, col. 6:19-21).
- Evidence for a Narrower Interpretation: The patent's background contrasts the invention with lyophilized products that are "clinically inconvenient, taking 15-30 mins" for reconstitution, suggesting "ready to use" means, at a minimum, avoiding such a complex and time-consuming step ('483 Patent, col. 6:56-58).
The Term: "stabilizing amount of an antioxidant"
- Context and Importance: This is a functional limitation. The dispute will likely center on whether the quantity of antioxidant in the accused products performs the claimed function of stabilization to the degree contemplated by the patent. Practitioners may focus on this term because similar definitional disputes over formulation components were central to prior litigation on related patents (Compl. ¶35).
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification defines "stabilizing amount" as "those amounts which increase or enhance the stability of the bendamustine in the compositions described herein," a broad, results-oriented definition ('483 Patent, col. 7:63-65).
- Evidence for a Narrower Interpretation: A party could argue that the term must be understood in the context of the patent's examples, which demonstrate specific antioxidants at particular concentrations achieving significant stability improvements. An argument could be made that an incidental or de minimis stabilizing effect would not meet this limitation.
VI. Other Allegations
Indirect Infringement
- The complaint alleges both induced and contributory infringement. Inducement is based on allegations that the defendants' proposed product labeling will instruct and encourage medical professionals to administer the product in an infringing manner (Compl. ¶¶59, 69). Contributory infringement is based on allegations that the defendants know their products are especially made or adapted for an infringing use and are not suitable for substantial non-infringing use (Compl. ¶¶60, 70).
Willful Infringement
- Willfulness is alleged based on the defendants' purported "full knowledge of the '483 patent and/or the application leading to the '483 patent" and proceeding "without a reasonable basis for believing" they would not be liable (Compl. ¶¶62, 72). The complaint's reference to prior litigation on related patents may be used to support these allegations (Compl. ¶35).
VII. Analyst’s Conclusion: Key Questions for the Case
- A key evidentiary question will be one of quantitative proof: can the plaintiff demonstrate through discovery that the defendants' proposed generic formulations, as described in their respective NDAs, will in fact exhibit "less than about 5% peak area response of total impurities" after 15 months of storage, as required by claim 1?
- A core issue will be one of functional scope: how will the court construe the term "stabilizing amount of an antioxidant"? Will any measurable increase in stability suffice, or must the term be interpreted to require a specific degree of stabilization attributable to the antioxidant, as might be suggested by the patent's examples?
- A third central question will concern the impact of prior litigation: how will the defendants' alleged concession of infringement on most elements of a claim from a related patent, which shares the same specification as the '483 patent, influence the court's view of the current infringement allegations and the defendants' claims of non-infringement or invalidity?