DCT
1:22-cv-01233
Nexus Pharma Inc v. Exela Pharma Sciences LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Nexus Pharmaceuticals, LLC (Illinois)
- Defendant: Exela Pharma Sciences, LLC (Delaware)
- Plaintiff’s Counsel: ArentFox Schiff LLP
- Case Identification: 1:22-cv-01233, D. Del., 07/05/2023
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant is a Delaware corporation.
- Core Dispute: Plaintiff alleges that Defendant’s AKOVAZ prefilled syringe, a ready-to-use ephedrine sulfate injection, infringes patents related to shelf-stable pharmaceutical compositions and methods of making them.
- Technical Context: The technology concerns sterile injectable pharmaceutical formulations, specifically creating ready-to-use ephedrine sulfate solutions that improve safety and convenience by eliminating the need for dilution by clinicians.
- Key Procedural History: The complaint alleges that Plaintiff provided Defendant with notice of the pending patent applications that matured into the patents-in-suit via letters starting in February 2022, potentially supporting allegations of willful infringement.
Case Timeline
| Date | Event |
|---|---|
| 2016-04-29 | Original AKOVAZ product (concentrated version) first approved by FDA |
| 2019-05-16 | Earliest Priority Date for ’369 and ’752 Patents |
| 2020-06-30 | Exela acquires the New Drug Application for AKOVAZ |
| 2020-11-10 | Exela files supplemental New Drug Application for the accused Akovaz PFS Product |
| 2022-02-01 | Nexus sends first of several letters to Exela regarding pending patent applications |
| 2022-08-30 | U.S. Patent No. 11,426,369 issues |
| 2022-10-11 | U.S. Patent No. 11,464,752 issues |
| 2023-07-05 | Complaint filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,426,369 - "Compositions comprising Ephedrine or an ephedrine salt and methods of making and using same"
- Issued: August 30, 2022
The Invention Explained
- Problem Addressed: The patent’s background section states that all FDA-approved formulations of ephedrine sulfate required dilution before administration, a process that is inconvenient, creates delays, and introduces a "significant and dangerous source of potential error" and contamination in clinical settings (’369 Patent, col. 1:24-39). Furthermore, ephedrine sulfate compositions are known to be susceptible to degradation from pH changes and humidity, leading to short shelf lives (’369 Patent, col. 1:63-2:2).
- The Patented Solution: The invention is a method for making a ready-to-use, premixed ephedrine sulfate composition that does not require reconstitution or dilution and remains stable after prolonged storage (’369 Patent, Abstract; col. 2:54-58). The method involves combining specific ingredients to form a batch solution, filtering and sanitizing, and sealing the solution in containers under conditions that ensure specific pH stability metrics are maintained over time (’369 Patent, col. 46:1-27).
- Technical Importance: This method enables the production of a safer and more convenient formulation of a critical drug used to treat hypotension, particularly in surgical settings (Compl. ¶24).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶53).
- The essential elements of Claim 1 are:
- A method of making a shelf-stable, ready-to-use ephedrine composition, comprising:
- combining ephedrine sulfate, sodium chloride or dextrose, and water to form a batch solution with specific concentrations (5 mg/mL ephedrine sulfate, 9 mg/mL sodium chloride or 5% dextrose) and no preservative;
- optionally contacting the batch solution with an acid or a base to obtain an initial pH level of 4.5 to 7;
- filtering the batch solution through a membrane filter;
- sanitizing one or more containers;
- placing not more than 20 mL of the filtered solution into the sanitized containers; and
- sealing each container to obtain a composition that is shelf-stable, defined as remaining within 0.5 pH units of the initial pH level during storage at specified conditions (25°C/60% relative humidity for at least 12 months or 40°C/75% relative humidity for at least 6 months).
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 11,464,752 - "Compositions comprising Ephedrine or an ephedrine salt and methods of making and using same"
- Issued: October 11, 2022
The Invention Explained
- Problem Addressed: As with the related ’369 Patent, this patent addresses the clinical risks and inconveniences associated with diluting concentrated ephedrine sulfate solutions prior to use, as well as the inherent instability of such compositions (’752 Patent, col. 1:24-39, 1:63-2:2).
- The Patented Solution: The invention is a finished pharmaceutical product, rather than a method. It claims a packaged, ready-to-use, single-use container (such as a vial or syringe) that holds a shelf-stable, sterilized ephedrine sulfate composition with specific ingredients and performance characteristics after long-term storage (’752 Patent, Abstract; col. 2:56-61).
- Technical Importance: This invention provides clinicians with the final, ready-to-administer drug product, directly improving patient safety by eliminating manual dilution steps (Compl. ¶18, ¶24).
Key Claims at a Glance
- The complaint asserts independent claim 10 (Compl. ¶93).
- The essential elements of Claim 10 are:
- A pharmaceutical product comprising:
- a packaged ready-to-use single-use container;
- comprising a shelf-stable sterilized pharmaceutical composition, which itself comprises:
- a packaged concentration of ephedrine sulfate of 5 mg/mL;
- 9 mg/mL sodium chloride;
- water;
- no preservative; and
- an initial pH level of about 4.5 to about 7.
- The composition must have, after storage under specified conditions (25°C/60% RH for 12 months or 40°C/75% RH for 6 months):
- an ephedrine sulfate concentration of at least 95% of the packaged concentration; and
- a pH level within 0.5 pH units of an initial pH level.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
III. The Accused Instrumentality
Product Identification
- Defendant’s AKOVAZ ephedrine sulfate 25 mg/5 mL (5 mg/mL) solution in a 5 mL prefilled syringe (“Akovaz PFS Product”) (Compl. ¶1, ¶25).
Functionality and Market Context
- The Akovaz PFS Product is described as a "premixed formulation" that is "ready to use" and does not require dilution prior to administration (Compl. ¶43, ¶95). It is provided as a sterile solution in a single-dose prefilled syringe intended for use in one patient during a single surgical procedure (Compl. ¶46, ¶95).
- The complaint alleges this product is a shelf-stable composition with a 24-month shelf life, marketed for treating clinically important hypotension (Compl. ¶12, ¶75, ¶96). It is alleged to be different from an older, concentrated version of Akovaz that was sold in vials and required dilution (Compl. ¶24, ¶28).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’369 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of making a shelf-stable, ready-to-use ephedrine composition, the method comprising: | The complaint alleges Exela makes the Akovaz PFS Product using a method that meets all claimed steps. | ¶54 | col. 45:46-48 |
| combining ephedrine sulfate, sodium chloride...and water to form a batch solution comprising an initial ephedrine sulfate level of 5 mg/mL, 9mg/mL sodium chloride...and no preservative; | The product label allegedly identifies 5 mg/mL ephedrine sulfate, 9 mg/mL sodium chloride, water, and no preservative. The complaint alleges on information and belief that these are combined in a batch process. | ¶57-59 | col. 46:1-5 |
| optionally contacting the batch solution with an acid or a base to obtain an initial pH level of the solution of 4.5 to 7; | The product packaging allegedly states it may contain agents for pH adjustment to achieve a final pH of 4.5-6.5, which is within the claimed range. | ¶61, ¶63 | col. 46:6-9 |
| filtering the batch solution through a membrane filter to obtain a filtered batch solution; | Alleged on information and belief that filtering is an essential manufacturing step to meet stringent FDA standards for injectable drugs. | ¶66-67 | col. 46:10-11 |
| sanitizing one or more containers; | Alleged on information and belief that sanitizing syringe containers is required to meet FDA standards for impurities and contaminants. | ¶70-71 | col. 46:17 |
| placing not more than 20 mL of the filtered batch solution into one of the one or more sanitized containers...; | The accused product is allegedly a 5 mL prefilled syringe, which contains a volume of less than 20 mL. | ¶73 | col. 46:18-20 |
| sealing each filled container to obtain sealed containers including a shelf-stable, ready-to-use ephedrine sulfate composition...that is within 0.5 pH units of the initial pH level during storage... | The product is allegedly sold in individually sealed syringes with a "tamper evident seal." The complaint alleges on information and belief that the product meets this stability requirement to obtain FDA approval for its 24-month shelf life. | ¶74-77 | col. 46:21-27 |
Identified Points of Contention
- Scope Questions: The complaint asserts infringement of a method patent based largely on analysis of the final product and inferences about standard manufacturing practices. A central question will be whether the final Akovaz PFS Product can only be made using the claimed process, which may trigger the burden-shifting provisions of 35 U.S.C. § 295, as referenced by the Plaintiff (Compl. ¶83).
- Technical Questions: The complaint alleges the final "sealing" and stability step is met based on the product’s 24-month FDA-approved shelf life. A key factual question is whether meeting FDA requirements for a 24-month shelf life necessarily means the product's pH remains "within 0.5 pH units of the initial pH level" as claimed, or if the FDA standard is different. The complaint raises the doctrine of equivalents as an alternative, suggesting the actual pH drift may be greater than 0.5 units (Compl. ¶78).
’752 Patent Infringement Allegations
| Claim Element (from Independent Claim 10) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical product comprising: a packaged ready-to-use single-use container comprising a shelf-stable sterilized pharmaceutical composition comprising: | The Akovaz PFS Product is alleged to be a packaged, ready-to-use, single-use, shelf-stable, and sterilized product in a prefilled syringe. | ¶95, ¶97 | col. 46:10-13 |
| a packaged concentration of ephedrine sulfate of 5 mg/mL, 9 mg/mL sodium chloride, water, no preservative, and an initial pH level of about 4.5 to about 7; | The product label allegedly confirms these exact component concentrations, the absence of preservatives, and a pH range of 4.5 to 6.5, which falls within the claimed range. | ¶99-100 | col. 46:14-18 |
| having, after storage...an ephedrine sulfate concentration of at least 95% of the packaged concentration, and a pH level within 0.5 pH units of an initial pH level. | The complaint alleges on information and belief that to obtain FDA approval for a 24-month shelf life, the product must meet stringent potency and stability requirements that satisfy these claimed limitations. | ¶101-104, ¶107 | col. 46:19-27 |
Identified Points of Contention
- Scope Questions: The dispute may center on whether the term "shelf-stable sterilized pharmaceutical composition" is strictly defined by the subsequent quantitative limitations (≥95% potency, ≤0.5 pH drift) or if it carries a broader meaning.
- Technical Questions: The primary technical question is evidentiary: what data supports the allegation that the accused product maintains at least 95% of its initial ephedrine sulfate concentration and a pH drift of no more than 0.5 units after 12 months at 25°C? The complaint relies on inference from the product's FDA approval rather than direct testing data, and also pleads infringement under the doctrine of equivalents as an alternative theory (Compl. ¶104-106).
V. Key Claim Terms for Construction
- The Term: "shelf-stable"
- Context and Importance: This term appears in both asserted independent claims and captures the core of the invention. Its construction is critical because the dispute centers on whether the accused product achieves the specific, long-term stability metrics patented by Nexus. Practitioners may focus on this term because it is arguably defined by the subsequent quantitative limitations within the claims themselves (e.g., pH stability and potency maintenance).
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification uses the term in a more general sense in the background section to describe the need for formulations that "remains stable and active after prolonged storage" without tying it to specific numerical values in that context (’369 Patent, col. 2:57-58).
- Evidence for a Narrower Interpretation: The body of both asserted claims appears to provide an explicit definition for "shelf-stable." Claim 1 of the '369 patent recites "sealed containers including a shelf-stable, ready-to-use ephedrine sulfate composition... that is within 0.5 pH units of the initial pH level during storage..." This structure suggests "shelf-stable" is not an abstract quality but is defined by the specific, objective criteria that follow.
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement of infringement, asserting that Exela is the New Drug Application holder and directs third-party contract manufacturers to produce the Akovaz PFS Product according to the approved (and allegedly infringing) product label and specifications (Compl. ¶80, ¶108).
- Willful Infringement: Willfulness is alleged based on pre-suit knowledge. The complaint states that Nexus sent multiple letters to Exela, starting over a year before the suit was filed, identifying the pending patent applications and, later, the issued patents, but alleges that Exela continued its infringing activities despite these notices (Compl. ¶38-39, ¶49, ¶87, ¶114).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of evidentiary proof versus regulatory inference: can the Plaintiff demonstrate through discovery that the accused Akovaz PFS Product literally meets the specific quantitative stability limitations recited in the claims (i.e., pH drift of ≤ 0.5 units and potency of ≥ 95% after storage), or will the case depend on persuading the court to infer these technical properties from the product's FDA approval and 24-month shelf life?
- For the '369 method patent, a key question will be one of process necessity: does the evidence show that the accused product, with its specific formulation and stability profile, is necessarily made by the patented process? This analysis may involve the burden-shifting framework of 35 U.S.C. § 295, which the Plaintiff has invoked.
- A secondary issue will be one of equivalents: if literal infringement of the stability limitations fails, the court will have to consider whether the accused product's likely stability performance (e.g., a potential pH drift greater than 0.5 units) is nonetheless insubstantially different from what is claimed, as argued in the alternative by the Plaintiff.