DCT
1:23-cv-00555
Nexus Pharma Inc v. Exela Pharma Sciences LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Nexus Pharmaceuticals, Inc. (Illinois)
- Defendant: Exela Pharma Sciences, LLC (Delaware)
- Plaintiff’s Counsel: Richards, Layton & Finger, P.A.
- Case Identification: Nexus Pharmaceuticals, Inc. v. Exela Pharma Sciences, LLC, 1:23-cv-00555, D. Del., 05/19/2023
- Venue Allegations: Venue is alleged to be proper in the District of Delaware based on Defendant’s incorporation in the state.
- Core Dispute: Plaintiff alleges that Defendant’s Akovaz prefilled syringe product infringes a patent related to ready-to-use, shelf-stable ephedrine sulfate pharmaceutical formulations.
- Technical Context: The technology concerns sterile injectable drugs used to treat hypotension during anesthesia, a clinical setting where the speed, safety, and convenience of ready-to-use formulations are significant.
- Key Procedural History: The complaint alleges that Plaintiff notified Defendant of its pending patent applications on multiple occasions prior to the patent-in-suit issuing. The complaint also notes that Plaintiff has previously filed suit against Defendant for infringement of two other patents from the same patent family.
Case Timeline
| Date | Event |
|---|---|
| 2016-04-29 | Original FDA approval for AKOVAZ (requiring dilution) |
| 2019-05-16 | ’398 Patent Priority Date |
| 2020-06-30 | Exela acquires the New Drug Application (NDA) for AKOVAZ |
| 2020-11-10 | Exela files supplemental NDA for Akovaz Prefilled Syringe (PFS) Product |
| 2022-02-01 | Nexus sends first of several letters to Exela regarding pending patent applications |
| 2023-02-07 | U.S. Patent No. 11,571,398 issues |
| 2023-05-19 | Complaint filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,571,398 - "Compositions comprising Ephedrine or an ephedrine salt and methods of making and using same"
- Patent Identification: U.S. Patent No. 11,571,398, "Compositions comprising Ephedrine or an ephedrine salt and methods of making and using same," issued February 7, 2023.
The Invention Explained
- Problem Addressed: The patent’s background section describes the drawbacks of existing ephedrine sulfate formulations, which required dilution prior to administration. This process is noted to be inconvenient, time-consuming, and a significant source of potential dosing errors and microbial contamination in critical clinical settings (’398 Patent, col. 1:24-35). Additionally, the patent notes that ready-to-use preparations of ephedrine were not known to be stable for extended periods (’398 Patent, col. 1:62-65).
- The Patented Solution: The invention is a premixed, ready-to-use, and shelf-stable formulation of ephedrine sulfate that does not require dilution. The patent discloses a specific composition—notably free of preservatives—that is claimed to maintain its chemical and physical stability (e.g., pH, concentration) over a long duration, thereby addressing the safety and convenience issues of prior art methods (’398 Patent, Abstract; col. 14:15-21).
- Technical Importance: The development of a stable, ready-to-use formulation provided a method for administering a critical drug for anesthesia-induced hypotension that could reduce the risk of human error and contamination associated with bedside compounding (’398 Patent, col. 1:46-58).
Key Claims at a Glance
- The complaint asserts infringement of at least Claim 1 of the ’398 Patent (Compl. ¶28).
- The essential elements of independent claim 1 are:
- A method for administering ephedrine to a subject for hypotension.
- The method comprises removing a syringe from sealed packaging.
- The syringe contains a sterilized, ready-to-use ephedrine composition with specific ingredients (5 mg/mL ephedrine sulfate, 9 mg/mL sodium chloride or 5% dextrose, water, no preservative) and an initial pH (about 4.5 to 7).
- The composition meets specific stability criteria after 6 or 12 months of storage (maintaining pH within 0.5 units, concentration at least 95%, and endotoxin levels not more than 7 EU/mg).
- The final step is injecting the composition into the subject without dilution.
- The complaint alleges infringement of "at least one claim," focusing its exemplary allegations on Claim 1 (Compl. ¶22, ¶29).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is Defendant’s Akovaz PFS Product, an ephedrine sulfate 25 mg/5 mL (5 mg/mL) solution in a 5 mL prefilled syringe (Compl. ¶1, ¶18).
Functionality and Market Context
- The complaint describes the Akovaz PFS Product as a "shelf-stable, ready-to-use" composition of ephedrine sulfate at a 5 mg/mL concentration that "requires no dilution prior to administration" (Compl. ¶18).
- It is sold for the "treatment of clinically important hypotension occurring in the setting of anesthesia" (Compl. ¶30). The product label, referenced as Exhibit B in the complaint, provides instructions for direct intravenous administration without dilution (Compl. ¶31, ¶35).
- Plaintiff alleges that Defendant’s marketing of the accused product threatens its market share and has led to price erosion (Compl. ¶23).
IV. Analysis of Infringement Allegations
- Claim Chart Summary: The complaint alleges that the Akovaz PFS Product and its method of use meet every limitation of Claim 1. The product’s FDA-approved label, which the complaint references as Exhibit B, is cited as evidence for several elements. For example, the complaint cites Section 11 of the product label to show the product's composition. (Compl. ¶33).
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of administering ephedrine to a subject having hypotension or at risk of developing hypotension in need thereof... | The Akovaz PFS Product's FDA-approved label states it is "indicated for the treatment of clinically important hypotension occurring in the setting of anesthesia." | ¶30 | col. 1:20-24 |
| removing, from sealed packaging, a syringe containing a sterilized ready-to-use ephedrine composition... | The Akovaz PFS Product is supplied as a sterilized, ready-to-use composition in prefilled syringes, which are provided in sealed packages of ten. | ¶32 | col. 14:31-35 |
| ...comprising: a packaged concentration of ephedrine sulfate of 5 mg/mL, 9 mg/mL sodium chloride or 5% dextrose, no preservative, water, an initial pH level of about 4.5 to about 7... | The product label allegedly states that each mL contains 5 mg ephedrine sulfate, 9 mg sodium chloride, and water for injection, with a pH range of 4.5 to 6.5, and makes no mention of a preservative. | ¶33 | col. 11:12-20 |
| having, after storage...a pH level within 0.5 pH units of the initial pH level, an ephedrine sulfate concentration at least 95% of the packaged concentration, and a bacterial endotoxin level not more than 7 EU/mg... | Alleged "upon information and belief" that the Akovaz PFS Product will meet these specific stability criteria when stored for the specified durations. | ¶34 | col. 45:18-24 |
| injecting the sterilized ephedrine composition from the syringe into the subject without diluting the sterilized ephedrine composition. | The product label allegedly instructs users to connect the syringe to an intravenous line and inject the composition, with no instruction for dilution. | ¶35 | col. 45:26-29 |
- Identified Points of Contention:
- Technical Question: The complaint alleges "upon information and belief" that the accused product meets the detailed stability limitations recited in Claim 1 (Compl. ¶34). A central question for the court will be a factual one: does the Akovaz PFS Product, as sold by Exela, actually maintain its pH, concentration, and endotoxin levels within the claimed ranges after being stored for the specified times and conditions? The resolution of this issue will likely depend on expert testing and analysis of the accused product during discovery.
V. Key Claim Terms for Construction
- The Term: "about"
- Context and Importance: This term modifies the claimed initial pH range of "about 4.5 to about 7." The construction of "about" will determine the precise boundaries of this range, which is critical for the infringement analysis. Practitioners may focus on this term because even a small deviation in the accused product's pH could be dispositive of infringement if the term is construed narrowly.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent uses the term "about" consistently when referring to concentrations and pH values, suggesting the patentee did not intend to be limited to the exact numerical values stated (’398 Patent, col. 2:8, col. 11:11-14). The breadth of the claimed range itself (4.5 to 7.0) could also support a more flexible interpretation.
- Evidence for a Narrower Interpretation: The specific examples in the patent disclose formulations with pH values within a much tighter range (5.6 to 6.2), which a party might argue should inform the meaning of "about" (’398 Patent, col. 17:36-38). The stability requirement that the pH remain "within 0.5 pH units" of the initial pH could also be argued to imply a need for precision that favors a narrower reading of "about."
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Exela induces infringement by selling the Akovaz PFS Product with labeling that "encourages and/or facilitates an individual to practice the method claimed" (Compl. ¶36). The basis for this allegation is the product's instructions for use, which allegedly direct medical personnel to perform the steps of the patented method (Compl. ¶31, ¶35).
- Willful Infringement: Willfulness is alleged based on pre-suit knowledge. The complaint asserts that Nexus sent letters to Exela regarding its pending patent applications on February 1, May 1, and July 25, 2022, and that Exela was also aware of prior litigation involving other patents in the same family (Compl. ¶20, ¶23, ¶42). This, the complaint alleges, constitutes actual notice and willful blindness to the infringing activity (Compl. ¶40).
VII. Analyst’s Conclusion: Key Questions for the Case
This case appears to present two primary questions for the court:
A central evidentiary question will be one of technical proof: Can Plaintiff demonstrate through discovery and expert testing that Defendant’s Akovaz PFS Product meets the specific, quantitative stability requirements recited in Claim 1? The allegation is currently made on "information and belief," making this a critical factual hurdle for the Plaintiff.
A key legal issue will be one of induced infringement: Does the FDA-approved labeling for the Akovaz PFS Product contain instructions that are specific enough to demonstrate an affirmative intent to encourage medical professionals to perform the complete, multi-step method claimed in the ’398 patent?