DCT
1:24-cv-00064
Eagle Pharma Inc v. Apotex Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Eagle Pharmaceuticals, Inc. (Delaware)
- Defendant: Apotex Inc. (Canadian) and Apotex Corp. (Delaware)
- Plaintiff’s Counsel: McCarter & English, LLP; Latham & Watkins LLP
- Case Identification: 1:24-cv-00064, D. Del., 04/15/2024
- Venue Allegations: Venue is alleged to be proper as Defendant Apotex Corp. is incorporated in Delaware, and Defendant Apotex Inc. is a foreign corporation subject to personal jurisdiction in the district.
- Core Dispute: Plaintiff alleges that Defendant’s generic Bendamustine Hydrochloride Injection product infringes patents related to stable, liquid formulations of the anti-cancer drug.
- Technical Context: The technology concerns ready-to-use liquid formulations of bendamustine designed to overcome the chemical instability and clinical inconvenience of prior art lyophilized (freeze-dried) powder versions.
- Key Procedural History: The complaint notes prior patent litigation between the parties, suggesting Defendants were aware of Plaintiff’s patent portfolio. Plaintiff also alleges it provided Defendants with actual notice of the patents-in-suit on or shortly after their issuance dates. The complaint references a prior Paragraph IV certification by Defendants on a related patent.
Case Timeline
| Date | Event |
|---|---|
| 2010-01-28 | Earliest Priority Date for '783 and '214 Patents |
| 2022-12-07 | FDA Approval for Apotex NDA Product |
| 2023-12-19 | U.S. Patent No. 11,844,783 Issues |
| 2023-12-20 | Eagle sends letter to Apotex regarding '783 Patent |
| 2024-01-16 | U.S. Patent No. 11,872,214 Issues |
| 2024-01-16 | Eagle sends letter to Apotex regarding '214 Patent |
| 2024-04-15 | First Amended Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,844,783 - "Formulations of Bendamustine," issued December 19, 2023
The Invention Explained
- Problem Addressed: The patent describes that bendamustine, an active ingredient in the cancer drug Treanda®, was supplied as a lyophilized powder that exhibited rapid degradation when reconstituted with water for administration, creating issues of chemical instability and clinical inconvenience (’783 Patent, col. 1:49-65).
- The Patented Solution: The invention is a stable, liquid formulation of bendamustine that avoids the need for reconstitution. It achieves long-term stability by dissolving the drug in a non-aqueous, pharmaceutically acceptable fluid, such as polyethylene glycol (PEG), and including a stabilizing amount of an antioxidant, such as monothioglycerol (’783 Patent, Abstract; col. 2:4-16). This creates a ready-to-use or ready-to-dilute product.
- Technical Importance: This approach provides a formulation with enhanced stability, which simplifies the clinical preparation process and reduces the risk of administering a degraded drug product (’783 Patent, col. 1:63-65).
Key Claims at a Glance
- The complaint asserts independent Claim 1 (Compl. ¶54).
- Essential elements of Claim 1 include:
- A method of treating leukemia in a human, which comprises providing a liquid bendamustine composition, diluting it, and intravenously administering it.
- The composition must contain bendamustine at a concentration of about 20 mg/mL to 60 mg/mL.
- The composition must contain a "pharmaceutically acceptable fluid consisting of polyethylene glycol" and optionally other specified solvents like ethanol.
- The composition must contain a "stabilizing amount of an antioxidant."
- The composition must meet a stability requirement: total impurities must be less than about 5% after at least 15 months of storage at 5 °C to 25 °C.
- The complaint reserves the right to assert other claims (Compl. ¶54).
U.S. Patent No. 11,872,214 - "Formulations of Bendamustine," issued January 16, 2024
The Invention Explained
- Problem Addressed: The patent addresses the same problem as the ’783 Patent: the rapid degradation of bendamustine in aqueous solutions, making lyophilized powders that require reconstitution clinically challenging (’214 Patent, col. 1:49-65).
- The Patented Solution: The solution is also the same as in the ’783 Patent: a long-term storage-stable liquid formulation using a non-aqueous fluid like PEG and a stabilizing antioxidant. The key distinction is that the ’214 Patent claims the product itself ("A sterile vial containing...") rather than a method of use (’214 Patent, Abstract; col. 2:4-16).
- Technical Importance: This invention provides the physical product—a stable, ready-to-use formulation of bendamustine—that offers greater convenience and reliability in a clinical setting (’214 Patent, col. 1:63-65).
Key Claims at a Glance
- The complaint asserts independent Claim 1 (Compl. ¶66).
- Essential elements of Claim 1 include:
- A sterile vial that contains a liquid bendamustine composition.
- The composition must contain about 100 mg of bendamustine at a concentration of about 25 mg/mL.
- The composition must contain a "pharmaceutically acceptable fluid consisting of polyethylene glycol" and optionally other specified solvents like ethanol.
- The composition must contain a "stabilizing amount of antioxidant."
- The composition must meet a stability requirement: total impurities must be less than about 5% after at least 15 months of storage at 5 °C to 25 °C.
- The complaint reserves the right to assert other claims (Compl. ¶66).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality 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 product is a generic liquid formulation of bendamustine hydrochloride submitted to the FDA under NDA No. 215033 (Compl. ¶2). The complaint alleges it is marketed as being "Therapeutically Equivalent to BELRAPZO®," Plaintiff's branded product (Compl. ¶57).
- According to the complaint, the Approved Labeling for the Apotex product specifies that each milliliter contains 25 mg bendamustine hydrochloride, polyethylene glycol 400, absolute ethanol, and 5 mg monothioglycerol (Compl. ¶¶38, 39, 49, 56). The product is supplied in a 100 mg/4 mL vial (Compl. ¶67).
- The complaint alleges the product is approved for an 18-month shelf life (Compl. ¶36).
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 |
|---|---|---|---|
| A method of treating leukemia in a human in need thereof comprising... | The Approved Labeling for the Apotex product allegedly recommends and instructs its use for treating patients with chronic lymphocytic leukemia. | ¶51 | col. 14:1-14 |
| providing a liquid bendamustine-containing composition comprising bendamustine...concentration...is from about 20 mg/mL to about 60 mg/mL; | Apotex imports and sells its Bendamustine Hydrochloride Injection, which is a liquid product with a concentration of 25 mg/mL. | ¶¶34, 38 | col. 3:18-19 |
| a pharmaceutically acceptable fluid consisting of polyethylene glycol and optionally...ethanol...; and | The Approved Labeling allegedly states the product contains polyethylene glycol and ethanol. | ¶39 | col. 4:51-53 |
| a stabilizing amount of an antioxidant; | The Approved Labeling allegedly states the product contains 5 mg/mL monothioglycerol, which the patent identifies as an antioxidant. | ¶49 | col. 4:20-22 |
| wherein the total impurities...is less than about 5% peak area response...after at least about 15 months...; | The complaint alleges that the FDA's approval of an 18-month shelf life for the product means this stability requirement must be met. | ¶36 | col. 2:41-51 |
| diluting the liquid bendamustine containing composition; and | The Approved Labeling allegedly instructs healthcare professionals to withdraw the required dose and transfer it to a 500 mL infusion bag for dilution. | ¶55 | col. 14:15-16 |
| intravenously administering the diluted composition to the human. | The Approved Labeling allegedly instructs intravenous administration of the diluted product. | ¶55 | col. 14:17-18 |
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...is about 25 mg/mL; | Apotex allegedly markets its product in a 100 mg/4 mL vial, which corresponds to a concentration of 25 mg/mL. | ¶67 | col. 3:24-25 |
| a pharmaceutically acceptable fluid consisting of polyethylene glycol and optionally...ethanol...; and | The product's Approved Labeling allegedly states that it contains polyethylene glycol and ethanol. | ¶67 | col. 4:51-53 |
| a stabilizing amount of antioxidant, | The Approved Labeling allegedly states the product contains 5 mg/mL monothioglycerol, which the patent identifies as an antioxidant. | ¶67 | col. 4:20-22 |
| wherein the total impurities...is less than about 5% peak area response...after at least about 15 months... | The complaint alleges that the product's FDA-approved 18-month shelf life demonstrates that it meets this stability limitation. | ¶36 | col. 2:41-51 |
Identified Points of Contention
- Scope Questions: The complaint preemptively addresses the use of sodium hydroxide in the manufacturing of the accused product (Compl. ¶¶40-48). A potential dispute may arise over the claim term "consisting of," which is legally restrictive. The question for the court will be whether the use of sodium hydroxide as a pH adjuster for a component (PEG) adds an unrecited element to the final "pharmaceutically acceptable fluid," thereby placing the accused product outside the claim's scope.
- Technical Questions: The complaint infers that the accused product meets the claims' stability limitations based on its FDA-approved 18-month shelf life (Compl. ¶36). What evidence does the complaint provide that the accused product's impurity profile, when measured by the specific HPLC method recited in the claims, is actually "less than about 5% peak area response" after 15 months? The case may require direct evidentiary proof beyond the fact of FDA approval.
V. Key Claim Terms for Construction
- The Term: "a pharmaceutically acceptable fluid consisting of..." (appears in '783 Claim 1 and '214 Claim 1)
- Context and Importance: Practitioners may focus on this term because "consisting of" is a term of art in patent law that creates a strong presumption that the claim is closed to unrecited elements. The complaint dedicates significant attention to arguing that sodium hydroxide, allegedly used to adjust the pH of the polyethylene glycol component, does not take the accused product outside this limitation (Compl. ¶¶40-48). The interpretation of this term could be dispositive of infringement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation (i.e., allowing for the pH adjuster): A party might argue that standard processing aids or impurities that do not materially alter the basic and novel properties of the composition are permitted even with "consisting of" language. The complaint suggests that using sodium hydroxide to bring a component (PEG) into compliance with its official monograph standard is a routine practice that should not defeat infringement (Compl. ¶43, ¶48).
- Evidence for a Narrower Interpretation (i.e., strictly excluding the pH adjuster): A party would argue that the plain meaning of "consisting of" forbids any unrecited substance in the final fluid. The fact that the patent specification details specific components for the fluid but never mentions sodium hydroxide or other pH adjusters could be used to argue that they were intentionally excluded from the claimed invention.
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement of the ’783 Patent. The allegations are based on Defendants' Approved Labeling, which allegedly instructs healthcare professionals to dilute and intravenously administer the product to treat leukemia, thereby performing the steps of the claimed method (Compl. ¶55). The complaint also points to marketing that encourages substitution for Plaintiff's product (Compl. ¶¶57-58).
- Willful Infringement: The complaint alleges willful infringement based on both pre- and post-suit knowledge of the patents. It alleges Defendants were aware of Plaintiff’s patent portfolio from prior litigation and from actively monitoring Plaintiff's patent filings (Compl. ¶¶60, 69). The complaint further alleges that Plaintiff sent letters to Defendants providing actual notice of the '783 and '214 patents on or immediately after their respective issue dates, but that Defendants continued to infringe (Compl. ¶¶60, 69).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of claim construction: can the restrictive term "consisting of," as used in the claims to define the formulation's fluid, be interpreted to permit the presence or use of unlisted substances like sodium hydroxide as a manufacturing pH adjuster, or does this practice place the accused product outside the literal scope of the patents?
- A key evidentiary question will be one of functional proof: does the accused product's FDA approval for an 18-month shelf life suffice to prove infringement of the claims' specific stability limitations, or will the court require direct evidence demonstrating that the product's total impurities fall below the 5% threshold as measured by the precise analytical method recited in the patents?