DCT

1:22-cv-05683

Nexus Pharma LLC v. Endo Operations Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:22-cv-05683, D.N.J., 03/09/2023
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendants maintain regular and established places of business in the district from which they allegedly manufacture, direct, control, or distribute the accused product.
  • Core Dispute: Plaintiff alleges that Defendants' ready-to-use prefilled syringe of ephedrine sulfate infringes three patents covering shelf-stable ephedrine sulfate compositions, methods of making them, and methods of administering them.
  • Technical Context: The technology concerns sterile, premixed, and shelf-stable injectable ephedrine sulfate formulations used to treat clinically significant hypotension, particularly in the setting of anesthesia.
  • Key Procedural History: The action was initiated as a consolidated case. The operative complaint is a First Amended Complaint, filed pursuant to a court order, which added U.S. Patent No. 11,571,398 to the lawsuit alongside the two previously asserted patents.

Case Timeline

Date Event
2019-05-16 Priority Date for '369, '752, and '398 Patents
2022-04-22 FDA approval of Defendants' NDA supplement for Accused Product
2022-08-30 U.S. Patent No. 11,426,369 issues
2022-10-11 U.S. Patent No. 11,464,752 issues
2023-02-07 U.S. Patent No. 11,571,398 issues
2023-03-09 First Amended 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"

The Invention Explained

  • Problem Addressed: The patent describes that prior FDA-approved ephedrine sulfate formulations required a ten-fold dilution before administration, a step that introduces risks of contamination, dosing errors, and treatment delays in clinical settings (’369 Patent, col. 1:25-31). Furthermore, existing ready-to-use preparations were not known to be stable for extended periods, such as more than 12 months (’369 Patent, col. 1:60-63).
  • The Patented Solution: The invention is a method for making a ready-to-use, shelf-stable ephedrine sulfate composition that does not require reconstitution or dilution prior to administration (’369 Patent, col. 2:55-63). The method involves combining specific ingredients, filtering, placing the solution in sanitized containers, sealing them, and ensuring the final composition maintains pH stability over long-term storage (’369 Patent, col. 16:11-21).
  • Technical Importance: This method provides a sterile, premixed, and stable formulation, which aims to reduce the risks of contamination and dosing errors associated with bedside dilution of the drug (’369 Patent, col. 1:30-43).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶96).
  • Claim 1 is a method claim with the following essential elements:
    • Combining ephedrine sulfate, a tonicity agent (sodium chloride or dextrose), and water to form a batch solution with specific concentrations and no preservative.
    • Optionally adjusting the solution's pH to a level of 4.5 to 7.
    • Filtering the solution through a membrane filter.
    • Sanitizing one or more containers.
    • Placing not more than 20 mL of the solution into a sanitized container.
    • Sealing the container to obtain a shelf-stable, ready-to-use composition.
    • Maintaining the pH level of the sealed composition within 0.5 pH units of the initial pH during storage under specified conditions for at least 6 or 12 months.
  • The complaint alleges infringement of "one or more claims," which may include dependent claims (Compl. ¶90).

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

The Invention Explained

  • Problem Addressed: Similar to the ’369 Patent, the background identifies the clinical risks and inconvenience associated with diluting concentrated ephedrine sulfate solutions before use, including potential for contamination and dosing errors (’752 Patent, col. 1:25-43).
  • The Patented Solution: The invention is a pharmaceutical product itself: a sterilized, ready-to-use ephedrine composition in a packaged syringe that remains stable and active after prolonged storage (’752 Patent, Abstract; col. 2:54-62). The claims define the product by its specific formulation and its performance characteristics after storage.
  • Technical Importance: This product provides clinicians with a premixed, stable, and sterile formulation, intended to mitigate the risks associated with bedside preparation and dilution (’752 Patent, col. 1:30-43).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶126).
  • Claim 1 is a product claim with the following essential elements:
    • A pharmaceutical product comprising a packaged syringe containing a sterilized, ready-to-use ephedrine composition.
    • The composition includes 5 mg/mL ephedrine sulfate, 9 mg/mL sodium chloride, no preservative, and water, with an initial pH of about 4.5 to 7.
    • The product has specific stability characteristics after storage for 6 or 12 months under defined conditions:
      • a pH level within 0.5 pH units of the initial pH.
      • an ephedrine sulfate concentration of at least 95% of the initial concentration.
      • a bacterial endotoxin level not more than 7 EU/mg.
  • The complaint alleges infringement of "one or more claims," which may include dependent claims (Compl. ¶120).

U.S. Patent No. 11,571,398 - "Compositions Comprising Ephedrine Or An Ephedrine Salt And Methods Of Making And Using Same"

Technology Synopsis

The patent addresses the risks of bedside dilution by claiming a method of administering ephedrine to a patient (’398 Patent, Abstract). The claimed method involves removing a pre-filled syringe containing a specific, stable, ready-to-use ephedrine composition from its packaging and injecting it into the patient without any intermediate dilution step (’398 Patent, col. 14:55-65).

Asserted Claims

Independent claim 1 is asserted (Compl. ¶169).

Accused Features

The complaint alleges that Defendants' marketing and FDA-approved package insert for their prefilled syringe product instruct and encourage healthcare providers to perform the patented method of administration (Compl. ¶¶165, 167, 170).

No probative visual evidence provided in complaint.

III. The Accused Instrumentality

Product Identification

  • The accused product is Defendants' Prefilled Syringe Product, which is an ephedrine sulfate injection, 25 mg/5 mL (5 mg/mL), in a 5 mL single-dose prefilled syringe, sold under NDA No. 213994 (Compl. ¶¶46, 72).

Functionality and Market Context

  • The product is described as a sterile, shelf-stable, ready-to-use ephedrine sulfate composition (Compl. ¶75). Its formulation is alleged to contain 5 mg/mL ephedrine sulfate, 9 mg/mL sodium chloride, and water, with a pH between 4.5 and 7 and no preservative (Compl. ¶75). The complaint alleges the product is marketed for use by healthcare professionals treating patients in a surgical setting and is shelf-stable for 6 and/or 12 months (Compl. ¶¶75, 79).

IV. Analysis of Infringement Allegations

'369 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
combining ephedrine sulfate, sodium chloride or dextrose, and water to form a batch solution comprising an initial ephedrine sulfate level of 5 mg/mL, 9 mg/mL sodium chloride...and no preservative Defendants' product is alleged to contain these components at these concentrations, from which the manufacturing step is inferred. ¶75 col. 16:16-21
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 final product is alleged to have a pH between 4.5 and 7, from which this manufacturing step is inferred. ¶75 col. 12:4-10
filtering the batch solution through a membrane filter to obtain a filtered batch solution The complaint alleges on information and belief that Defendants filter their product through a membrane. ¶75 col. 16:32-37
sanitizing one or more containers; placing not more than 20 mL of the filtered batch solution into one of the one or more sanitized containers The product is provided in a 5 mL prefilled syringe, alleged to be a sanitized and sterilized container. ¶¶72, 75 col. 16:38-46
sealing each filled container to obtain sealed containers including a shelf-stable, ready-to-use ephedrine sulfate composition The product is provided as a sealed, ready-to-use prefilled syringe. ¶75 col. 16:38-46
maintaining a pH level of the shelf-stable, ready-to-use ephedrine sulfate composition...that is within 0.5 pH units of the initial pH level during storage...for at least 12 months or...6 months The complaint alleges the product is shelf-stable for 6 and/or 12 months, from which this stability characteristic is inferred. ¶75 col. 8:1-17
  • Identified Points of Contention:
    • Scope Questions: The claim is for a method of making a product. The complaint's allegations appear to be based primarily on the characteristics of the final product as described on its label. A central issue may be whether Plaintiff can prove that Defendants' actual manufacturing process includes each claimed step, especially for steps like filtering and sanitizing, which are alleged on "information and belief."
    • Technical Questions: A key evidentiary question concerns the final limitation regarding pH stability. The complaint infers this property from a general allegation of shelf stability. What evidence does the complaint provide that the manufacturing process results in a product that specifically maintains its pH within 0.5 units of the initial level over the prescribed time and conditions?

'752 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical product comprising: a packaged syringe containing a sterilized ready-to-use ephedrine composition... The accused product is a 5 mL single-dose prefilled syringe. ¶72 col. 11:55-60
a packaged concentration of ephedrine sulfate of 5 mg/mL, 9 mg/mL sodium chloride, no preservative, water, and an initial pH level of about 4.5 to about 7 The complaint alleges the accused product's FDA-approved label describes these exact compositional and pH characteristics. ¶75 col. 11:1-22
having, after storage...a pH level within 0.5 pH units of the initial pH level This property is inferred from the allegation that the product is shelf-stable for 6 and/or 12 months. ¶75 col. 8:1-17
an ephedrine sulfate concentration of at least 95% of the packaged concentration This property is also inferred from the allegation that the product is shelf-stable. ¶75 col. 6:35-48
a bacterial endotoxin level not more than 7 EU/mg This is a standard requirement for sterile injectable products subject to FDA approval. ¶126 col. 13:4-12
  • Identified Points of Contention:
    • Scope Questions: The dispute may focus on the "having, after storage" limitations. These clauses define the product by its functional stability over time. The question will be whether a product that has not yet undergone the full storage period but is designed and intended to meet those criteria falls within the claim scope.
    • Technical Questions: What evidence does the complaint provide that the accused product actually exhibits the claimed stability profile (i.e., maintaining pH within 0.5 units and concentration at ≥95%) after the specified storage periods? This is a technical property that likely requires empirical testing, which is not detailed in the complaint.

V. Key Claim Terms for Construction

  • The Term: "shelf-stable" (from '369 Patent, Claim 1)

    • Context and Importance: This term is fundamental to the patent's asserted novelty over prior art compositions. Its construction will determine the specific stability requirements that must be met by both the claimed method and the accused product. Practitioners may focus on this term because the complaint's infringement theory relies on the accused product being "shelf-stable."
    • Evidence for a Broader Interpretation: The specification does not appear to provide an explicit definition, which could support giving the term its plain and ordinary meaning to one of skill in the art of pharmaceutical formulations.
    • Evidence for a Narrower Interpretation: The claim language itself links "shelf-stable" to a specific functional outcome: maintaining a pH level within 0.5 units of the initial pH for at least 12 or 6 months under specified conditions. A party could argue this limitation serves as an implicit definition within the context of this specific claim.

  • The Term: "ready-to-use" (from asserted claims of all three patents)

    • Context and Importance: This term describes the core clinical and commercial advantage of the invention. The accused product is also marketed as "ready-to-use," making the term's meaning central to the infringement analysis.
    • Evidence for a Broader Interpretation: A party could argue for a general meaning of not requiring any preparation before administration.
    • Evidence for a Narrower Interpretation: The patent specification repeatedly contrasts the invention with prior art formulations that "must be diluted ten-fold before administration" (’369 Patent, col. 1:29-31). This consistent distinction may support a narrower construction where "ready-to-use" specifically means that the composition does not require dilution.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement for all three patents. For the '369 and '752 Patents, it alleges Defendants direct and instruct contract manufacturers to make and use the infringing product (Compl. ¶¶97, 127). For the method-of-use '398 Patent, the complaint alleges inducement based on Defendants' marketing and FDA-approved package insert, which allegedly instruct and encourage healthcare providers to administer the product in an infringing manner (Compl. ¶¶165, 167).
  • Willful Infringement: The complaint alleges willfulness based on Defendants' alleged knowledge of the patents-in-suit since their respective issue dates. It further alleges that Defendants tracked the prosecution of the underlying patent applications, suggesting pre-suit knowledge of the claimed inventions (Compl. ¶¶87-88, 99, 129, 172).

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

  • A core issue will be one of process inference: for the method claims of the ’369 Patent, can the Plaintiff prove through discovery that Defendants' manufacturing process performs every claimed step, given that the complaint's allegations rely heavily on inferring the process from the final product's characteristics?
  • A key evidentiary question will be one of demonstrated stability: for the product claims of the ’752 Patent, what empirical evidence will be presented to establish that Defendants' product actually meets the specific functional limitations of maintaining pH and potency after the claimed storage periods, as these are central to the claim language?
  • A central question for the ’398 Patent will be one of induced infringement: do the specific instructions in the accused product's package insert and marketing materials rise to the level of actively encouraging or instructing healthcare providers to perform all steps of the claimed method of administration, thereby showing the specific intent required for inducement?