Nexus Pharma LLC v. Hikma Pharma USA Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Nexus Pharmaceuticals, LLC (Illinois)
  • Defendant: Hikma Pharmaceuticals USA Inc. (Delaware)
  • Plaintiff’s Counsel: Richards, Layton & Finger, P.A.
• Case Identification: 1:25-cv-00018, D. Del., 03/25/2025
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant is a corporation organized and existing under the laws of Delaware.
• Core Dispute: Plaintiff alleges that Defendant’s prefilled-syringe ephedrine sulfate product infringes three patents related to stable, ready-to-use pharmaceutical compositions and methods of making and administering the same.
• Technical Context: The technology concerns sterile, injectable pharmaceutical formulations designed to be shelf-stable and ready for immediate use without dilution, aiming to improve safety and convenience in clinical settings.
• Key Procedural History: The operative pleading is a First Amended Complaint. The complaint alleges that Defendant was aware of and tracked Plaintiff's patent applications during their prosecution at the U.S. Patent and Trademark Office.

Case Timeline

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

U.S. Patent No. 11,464,752 - "Compositions Comprising Ephedrine Or An Ephedrine Salt And Methods Of Making And Using Same"

• Patent Identification: 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 Compl. ¶15

The Invention Explained

• Problem Addressed: The patent family's background section describes that all previously FDA-approved ephedrine sulfate formulations required dilution before administration, a process that is inconvenient, introduces delays, and creates a significant risk of contamination or dosing errors in clinical settings ’369 Patent, col. 1:24-34 Additionally, ephedrine sulfate compositions are known to be susceptible to degradation from light, pH changes, and humidity, limiting their shelf life ’369 Patent, col. 1:63-65
• The Patented Solution: The invention is a premixed, "ready-to-use" sterile pharmaceutical composition of ephedrine sulfate that does not require dilution before injection ’369 Patent, col. 2:54-63 As described in the specification, the formulation comprises specific concentrations of ephedrine sulfate and an isotonic agent (e.g., sodium chloride) in water, without preservatives, and is designed to remain stable in its potency and pH level for an extended period ’369 Patent, col. 11:4-20
• Technical Importance: This approach provides a safer and more efficient therapeutic option for treating clinically important hypotension, particularly in urgent settings like operating rooms, by eliminating the risks associated with bedside dilution ’369 Patent, col. 1:30-43

Key Claims at a Glance

• The complaint asserts independent claim 1 Compl. ¶47
• The essential elements of claim 1 include:
  • A pharmaceutical product comprising a packaged syringe containing a sterilized ready-to-use ephedrine composition.
  • The composition comprises ephedrine sulfate at 5 mg/mL, 9 mg/mL sodium chloride, water, no preservative, and an initial pH of about 4.5 to 7.
  • The product, after specified storage conditions (e.g., 12 months at 25° C./60% RH), maintains a pH within 0.5 units of the initial pH, an ephedrine sulfate concentration of at least 95% of the packaged concentration, and a bacterial endotoxin level not more than 7 EU/mg.

U.S. Patent No. 11,426,369 - "Compositions Comprising Ephedrine Or An Ephedrine Salt And Methods Of Making And Using Same"

• Patent Identification: 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 Compl. ¶19

The Invention Explained

• Problem Addressed: The technical problems are identical to those described for the ’752 Patent: the risks and inconveniences of diluting concentrated drug formulations and the inherent instability of ephedrine sulfate compositions ’369 Patent, col. 1:24-65
• The Patented Solution: This patent claims a specific method for manufacturing the shelf-stable, ready-to-use ephedrine sulfate composition. The method comprises the steps of combining the specific ingredients to form a batch solution, optionally adjusting pH, filtering the solution, sanitizing containers (e.g., syringes), filling them with a specified volume, and sealing them to create the final product ’369 Patent, Abstract; col. 46:1-20 A key element of the claimed method is the final step of maintaining the pH level of the composition within 0.5 pH units of its initial level during long-term storage under specified conditions ’369 Patent, col. 46:21-30
• Technical Importance: The invention provides a defined, reproducible manufacturing process designed to ensure the sterility and long-term stability of a ready-to-use ephedrine sulfate product, addressing the quality control challenges associated with both compounded preparations and traditional formulations ’369 Patent, col. 1:50-61

Key Claims at a Glance

• The complaint asserts independent claim 1 Compl. ¶89
• The essential elements of claim 1 include:
  • A method of making a shelf-stable, ready-to-use ephedrine sulfate composition.
  • The method comprises steps of: combining ephedrine sulfate (5 mg/mL), sodium chloride (9 mg/mL) or dextrose, and water with no preservative; optionally adjusting pH; filtering; sanitizing containers; placing not more than 20 mL into the containers; and sealing.
  • The method concludes with a step of maintaining the pH level within 0.5 units of the initial level during storage under specified conditions (e.g., 12 months at 25° C./60% RH).

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 Compl. ¶23

Technology Synopsis

This patent claims a method of administering ephedrine to a subject for treating hypotension Compl. ¶¶ 25, 138 The method comprises removing a syringe containing the specific sterilized, ready-to-use, and shelf-stable ephedrine composition from sealed packaging and injecting the composition into the subject without an intermediate step of dilution Compl. ¶139

Asserted Claims

Independent claim 1 is asserted Compl. ¶139

Accused Features

The complaint alleges that Defendant induces infringement of this method patent by marketing its product with an FDA-approved package insert that instructs healthcare providers to perform the claimed steps of administration Compl. ¶¶ 135, 137, 155

III. The Accused Instrumentality

Product Identification

Defendant Hikma’s ephedrine sulfate injection, 25 mg/5 mL (5 mg/mL), in a prefilled-syringe presentation, which was approved by the FDA under Abbreviated New Drug Application (ANDA) No. 217721 Compl. ¶¶ 2, 27

Functionality and Market Context

• The accused product is described on its FDA-approved label as a "premixed formulation" that is ready to use and should not be diluted Compl. ¶50 It is a "clear, colorless, sterile solution for intravenous injection" Compl. ¶52 The product is supplied in a "single-dose 5mL prefilled syringe" Compl. ¶50, which is packaged in sealed plastic overwrap Compl. ¶51 The complaint references a depiction in the product instructions of the syringe being removed from this "plastic overwrap" Compl. ¶51
• According to its label, the formulation contains 5 mg of ephedrine sulfate and 8.6 mg of Sodium Chloride per mL in water for injection, with a pH range of 4.5 to 6.5, and it contains no preservative Compl. ¶54
• The complaint alleges that Defendant began commercial marketing of the accused product on or about December 20, 2024 Compl. ¶31

IV. Analysis of Infringement Allegations

'752 Patent Infringement Allegations

Identified Points of Contention

• Technical and Scope Questions: The asserted claim requires "9 mg/mL sodium chloride," while the accused product's label specifies "8.6 mg Sodium Chloride" per mL Compl. ¶54 This raises the question of whether 8.6 mg/mL falls within the literal scope of the claim or, alternatively, whether it can be proven to be an equivalent concentration under the doctrine of equivalents.
• Evidentiary Questions: The complaint's allegations regarding the stability limitations (maintaining pH and concentration after storage) are based on "information and belief" and inferences drawn from FDA regulatory standards, not explicit statements on the product's label Compl. ¶¶55-58 A key question will be what evidence is produced during discovery to demonstrate that the accused product in fact meets these specific claimed performance metrics under the specified storage conditions.

'369 Patent Infringement Allegations

Identified Points of Contention

• Evidentiary Questions: The allegations of infringement for this method claim rely almost entirely on "information and belief" regarding Defendant's confidential manufacturing process Compl. ¶¶94, 100, 102 A central issue will be whether discovery reveals that Defendant's actual process includes the specific sequence of steps (batching, filtering, sanitizing, filling) as required by the claim.
• Technical Questions: As with the ’752 Patent, the variance between the claimed "9 mg/mL" sodium chloride in the "combining" step and the accused product's labeled "8.6 mg/mL" concentration raises a question of literal scope and equivalence that the court may need to resolve.

V. Key Claim Terms for Construction

Term: "9 mg/mL sodium chloride" (’752 Patent, Claim 1; ’369 Patent, Claim 1)

• Context and Importance: This term is critical because the accused product's label specifies "8.6 mg Sodium Chloride" per mL Compl. ¶54 The infringement analysis will depend on whether this concentration falls within the scope of the claim term. Practitioners may focus on this term because a purely numerical limitation without modifiers like "about" can be a focal point for non-infringement arguments.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The specification describes the function of sodium chloride as an "isotonic agent" and provides "about 9 mg/mL" as an exemplary isotonic amount, suggesting the precise number is not the only possibility contemplated by the inventors ’369 Patent, col. 11:6-9
  • Evidence for a Narrower Interpretation: The asserted independent claims of both the ’752 and ’369 patents recite the precise value "9 mg/mL" without the modifier "about." A party could argue that by omitting "about" in the claim while using it in the specification, the patentee intended to claim the exact concentration, distinguishing it from other possible amounts.

Term: "ready-to-use" (’752 Patent, Claim 1; ’369 Patent, Claim 1)

• Context and Importance: This term captures the central feature of the invention, distinguishing it from prior art formulations that required dilution. Its construction will be fundamental to defining the scope of the patented product and method.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The patent specification repeatedly defines the term functionally, stating that "ready-to-use" compositions are those that "do not require reconstitution or dilution prior to administration to a subject" ’369 Patent, col. 2:60-63 This suggests any formulation that can be administered directly from its primary container meets the definition.
  • Evidence for a Narrower Interpretation: The background section contrasts the invention with prior art formulations that "must be diluted ten-fold before administration" ’369 Patent, col. 1:28-29 While this supports the functional definition, a party might explore the prosecution history to determine if any arguments made to the patent office could have narrowed the scope of what qualifies as "ready-to-use."

VI. Other Allegations

Indirect Infringement

The complaint alleges that Defendant induces infringement of the ’398 method-of-use patent by marketing its product with an FDA-approved package insert that allegedly directs and encourages healthcare providers to perform the claimed steps of removing the pre-filled syringe from packaging and injecting the contents without dilution Compl. ¶¶135, 137, 142, 155 General allegations of inducing or contributing to infringement are also made for the ’752 and ’369 patents, based on directing third-party contract manufacturers Compl. ¶¶48, 90

Willful Infringement

The complaint alleges that Defendant had knowledge of the patents-in-suit since at least their respective issue dates, and was aware of the underlying patent applications during their prosecution Compl. ¶¶37, 38 It is alleged that Defendant's launch and ongoing sale of the accused product despite this knowledge constitutes willful infringement Compl. ¶¶61, 112, 158

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

• A core issue will be one of evidentiary proof: can Plaintiff produce evidence through discovery to substantiate its "information and belief" allegations that Defendant's product meets the specific, quantitative stability metrics recited in the claims, and that Defendant's confidential manufacturing process contains the specific steps of the asserted method claim?
• A second key issue will be one of claim scope: can the term "9 mg/mL sodium chloride," recited without modifiers in the asserted claims, be construed to cover the accused product's formulation containing 8.6 mg/mL of sodium chloride, either literally or under the doctrine of equivalents?
• A final question relates to intent for indirect infringement: for the method-of-use claims, the analysis may turn on whether Defendant's product label and marketing materials demonstrate the specific intent to encourage healthcare providers to perform all steps of the patented method of administration.