DCT
1:24-cv-04719
Endo USA Inc v. Nexus Pharma LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Endo USA, Inc. (Delaware) and Endo Operations Limited (Ireland)
- Defendant: Nexus Pharmaceuticals, LLC (Illinois)
- Plaintiff’s Counsel: Axinn, Veltrop & Harkrider LLP; McDonnell Boehnen Hulbert & Berghoff LLP
- Case Identification: 1:24-cv-04719, N.D. Ill., 07/10/2024
- Venue Allegations: Venue is alleged to be proper based on Defendant's principal place of business being located within the district, and on alleged acts of infringement occurring in the district. The complaint also asserts that Defendant admitted jurisdiction and venue were proper in this district in a previous action.
- Core Dispute: Plaintiff alleges that Defendant’s ready-to-use ephedrine syringe products infringe three patents related to stable, ready-to-use ephedrine compositions and the methods for their preparation and use.
- Technical Context: The technology pertains to pharmaceutical formulations, specifically stable, injectable ephedrine solutions that do not require dilution before administration, which is intended to reduce medical errors and save time in clinical settings.
- Key Procedural History: The complaint notes that Defendant previously filed a declaratory judgment action in 2021 seeking a finding of non-infringement of the ’845 patent, which ultimately settled. This prior litigation is cited as the basis for alleging willful infringement of the ’845 patent.
Case Timeline
| Date | Event |
|---|---|
| 2020-01-22 | Earliest Priority Date for ’845, ’121, and ’710 Patents |
| 2020-04-17 | FDA Approval for Nexus’s Emerphed RTU Vials |
| 2020-12-22 | U.S. Patent No. 10,869,845 Issued |
| 2021-08-17 | Nexus files Declaratory Judgment action regarding ’845 Patent |
| 2022-11-08 | U.S. Patent No. 11,491,121 Issued |
| 2023-03-01 | FDA Approval for Nexus’s Emerphed RTU Syringes |
| 2024-07-09 | U.S. Patent No. 12,029,710 Issued |
| 2024-07-10 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,869,845 - “EPHEDRINE COMPOSITIONS AND METHODS,” Issued December 22, 2020
The Invention Explained
- Problem Addressed: The patent describes a need in the art for ephedrine injection formulations that are "ready to use for injection in patients, are storage stable and pH stable, and which do not significantly drift in pH over time" (’845 Patent, col. 2:8-11). Previously available FDA-approved ephedrine products were concentrated formulations that required dilution, a process that could introduce errors, contamination, and delay in emergency situations, while the resulting diluted solutions were not pH stable for storage (’845 Patent, col. 2:51-64; Compl. ¶22).
- The Patented Solution: The patent discloses a premixed, "ready-to-use" ephedrine solution that is both storage-stable and pH-stable (’845 Patent, col. 3:60-63). The solution's stability is achieved by combining specific concentrations of ephedrine and sodium chloride, using acetic acid as a pH adjuster, and setting the initial pH to a narrow range of 4.6 to 4.8, which was found to surprisingly minimize pH drift and impurity formation over time (’845 Patent, col. 6:1-13).
- Technical Importance: The invention provides a commercially sterile ephedrine product that eliminates the need for bedside dilution, thereby aiming to reduce the risk of medication errors and contamination while saving time for healthcare providers (Compl. ¶23).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶33).
- The essential elements of independent claim 1 include:
- A storage-stable, sterile ephedrine ready-to-use solution composition, comprising:
- about 5 mg/mL of ephedrine or a pharmaceutically acceptable salt thereof;
- about 9 mg/mL of sodium chloride;
- a pH adjuster comprising acetic acid; and water;
- wherein the initial adjusted pH of the composition is in the range of 4.6 to 4.8;
- wherein the pH drift is less than 0.5 after 6 months of storage at standard conditions; and
- wherein the composition contains about 5% or less total impurities after 6 months of storage.
- The complaint seeks relief for infringement of "one or more claims" of the patent (Compl., Prayer for Relief ¶A).
U.S. Patent No. 11,491,121 - “EPHEDRINE COMPOSITIONS AND METHODS,” Issued November 8, 2022
The Invention Explained
- Problem Addressed: The ’121 Patent addresses the same technical problem as the ’845 Patent: the lack of stable, ready-to-use ephedrine formulations and the risks associated with diluting concentrated versions (’121 Patent, col. 2:2-11).
- The Patented Solution: Rather than claiming the composition itself, this patent claims a method of preparing the storage-stable ephedrine solution. The claimed method recites the specific steps of combining ephedrine and sodium chloride in an aqueous solution to the claimed concentrations and then "adjusting a pH of the aqueous solution... to a range of 4.6 to 4.8" using a solution that contains acetic acid (’121 Patent, col. 23:15-20). This process is claimed to result in a composition with the desired low pH drift and impurity profile.
- Technical Importance: The patent protects the specific manufacturing process required to create the stable formulation, creating a distinct layer of intellectual property protection from the product-by-process claims of the ’845 Patent (Compl. ¶23).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶46).
- The essential elements of independent claim 1 include:
- A method of preparing a storage-stable, sterile ephedrine ready-to-use solution composition, comprising:
- combining ephedrine sulfate and sodium chloride to concentrations of about 5 mg/mL and about 9 mg/mL, respectively;
- adjusting the pH of the solution to a range of 4.6 to 4.8;
- wherein the pH is adjusted with a solution containing acetic acid; and
- wherein the resulting composition exhibits a pH drift of less than 0.5 and contains 5% or less total impurities after 6 months of storage.
- The complaint seeks relief for infringement of "one or more claims" of the patent (Compl., Prayer for Relief ¶E).
U.S. Patent No. 12,029,710 - “EPHEDRINE COMPOSITIONS AND METHODS,” Issued July 9, 2024
Technology Synopsis
This patent addresses the same technical problem of creating a stable, ready-to-use ephedrine formulation (’710 Patent, col. 2:52-65). It protects a method of treating hypotension by administering the specific storage-stable composition, as defined by its ingredients and stability properties, from a pre-filled syringe (’710 Patent, Abstract, col. 23:11-26).
Asserted Claims
The complaint asserts infringement of at least independent claim 1 (Compl. ¶58).
Accused Features
The complaint alleges that Defendant induces infringement by marketing its Emerphed RTU Syringes with an FDA-approved label that instructs healthcare providers to administer the product to treat hypotension, which allegedly constitutes performance of the claimed method (Compl. ¶¶59, 62-63).
III. The Accused Instrumentality
Product Identification
The primary accused products are "Nexus's Emerphed RTU Syringes," which are described as ephedrine sulfate injections (5 mg/mL) in 5 mL and 10 mL prefilled syringes (Compl. ¶26). The complaint also references "Nexus's Emerphed RTU Vials" (Compl. ¶24).
Functionality and Market Context
The accused syringes are marketed as ready-to-use formulations of ephedrine sulfate that do not require further dilution prior to administration (Compl. ¶26, 29). The complaint references a press release in which Defendant's Chief Operating Officer stated excitement to "introduce the next generation of ready-to-administer ephedrine sulfate products once again" (Compl. ¶29, citing Ex. D). The products are alleged to be manufactured in Italy for Nexus and imported into the United States for sale through major pharmaceutical wholesalers (Compl. ¶¶30-31).
IV. Analysis of Infringement Allegations
’845 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A storage-stable, sterile ephedrine ready-to-use solution composition, comprising: | Nexus's Emerphed RTU Syringes are alleged to contain such a composition. | ¶35 | col. 21:50-51 |
| about 5 mg/mL of ephedrine or a pharmaceutically acceptable salt thereof; | The product label allegedly states the syringes contain 5 mg/mL of ephedrine sulfate. | ¶36 | col. 21:51-53 |
| about 9 mg/mL of sodium chloride; | The product label allegedly states the syringes contain 9 mg/mL of sodium chloride. | ¶37 | col. 21:54-55 |
| a pH adjuster comprising acetic acid; | Alleged on "information and belief" that the product contains acetic acid or satisfies the limitation under the doctrine of equivalents. | ¶38 | col. 21:56 |
| wherein the initial adjusted pH of the composition is in the range of 4.6 to 4.8; | Alleged on "information and belief" that the product has this initial pH or satisfies the limitation under the doctrine of equivalents. | ¶39 | col. 21:59-60 |
| wherein the pH drift of the composition is less than 0.5 after storage for 6 months... | Alleged on "information and belief" that the product's composition meets this stability requirement or satisfies the limitation under the doctrine of equivalents. | ¶40 | col. 21:61-64 |
| wherein the composition contains about 5% or less total impurities after storage for 6 months... | Alleged on "information and belief" that the product's composition meets this purity requirement or satisfies the limitation under the doctrine of equivalents. | ¶41 | col. 22:1-4 |
’121 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of preparing a storage-stable, sterile ephedrine ready-to-use solution composition, comprising: | Nexus is alleged to prepare its Emerphed RTU Syringes using the claimed method, or an equivalent one. | ¶49-50 | col. 23:7-10 |
| combining in an aqueous solution ephedrine or ephedrine sulfate and sodium chloride to a concentration of about 5 mg/mL ephedrine and about 9 mg/mL sodium chloride; | Alleged on "information and belief" that Nexus's manufacturing process involves this combination step. | ¶49 | col. 23:11-14 |
| adjusting a pH of the aqueous solution... to a range of 4.6 to 4.8... wherein the pH is adjusted with a solution containing acetic acid; | Alleged on "information and belief" that Nexus's manufacturing process involves adjusting the pH to this range using acetic acid. | ¶50 | col. 23:15-20 |
| wherein a pH drift of the adjusted ephedrine composition is less than 0.5 after storage for 6 months... and wherein the composition contains about 5% or less total impurities... | Alleged on "information and belief" that the method used by Nexus results in a product meeting these stability and purity characteristics. | ¶51-52 | col. 23:21-24; col. 24:1-4 |
- Identified Points of Contention:
- Technical Questions: A primary point of contention will likely be the composition's non-disclosed characteristics. The complaint relies on "information and belief" for the presence of acetic acid, the initial pH of 4.6-4.8, and the long-term stability and impurity profiles (Compl. ¶¶38-41). This raises the evidentiary question of whether discovery and testing will confirm that the accused product literally meets these limitations. The repeated pleading of the doctrine of equivalents for these same elements suggests Plaintiffs anticipate a potential defense of non-literal infringement (Compl. ¶¶38-41).
- Scope Questions: The claims use the term "about" to qualify concentrations (e.g., "about 5 mg/mL"). This raises the question of how much deviation from the stated value is permissible under the claim, a common issue in pharmaceutical patent litigation.
V. Key Claim Terms for Construction
The Term: "a pH adjuster comprising acetic acid" (’845 Patent, Claim 1)
- Context and Importance: This term is critical because the complaint alleges the use of acetic acid on "information and belief," signaling it is not disclosed on the product's label and may be a point of dispute (Compl. ¶38). The patent itself emphasizes that adjusting the pH with acetic acid to a specific range is key to achieving the invention's stability (’845 Patent, col. 6:28-33).
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The use of the open-ended term "comprising" may support an interpretation that the pH adjuster must contain acetic acid but could also include other substances. The specification lists numerous other potential "acidic pH adjusters" such as hydrochloric and citric acid, which could be argued to place less emphasis on acetic acid alone (’845 Patent, col. 11:26-34).
- Evidence for a Narrower Interpretation: The specific working examples and stability data tables in the patent focus exclusively on compositions adjusted with acetic acid (’845 Patent, Tables 2-11). A party might argue that the specification teaches acetic acid as being essential to solving the stated problem, thus implicitly defining the "pH adjuster" as one where acetic acid is the operative agent.
The Term: "ready-to-use" (’845 Patent, Claim 1)
- Context and Importance: This term captures the core purpose of the invention. Practitioners may focus on this term because its definition will determine whether any product requiring even minor pre-administration handling falls outside the patent's scope.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides an explicit definition, stating that "ready-to-use" refers to a formulation that "does not require reconstitution or dilution prior to administration to a patient" (’845 Patent, col. 3:60-63). This language could be argued to cover any product that is directly injectable without being diluted from a concentrate.
- Evidence for a Narrower Interpretation: A party could argue that, in the context of the problems described in the Background section (criticizing multi-step processes, risk of error, and time), the term implies a higher standard of immediacy, potentially excluding products that require any form of activation or preparation, however minor.
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement of the ’710 patent, which claims a method of treatment. The allegations are based on Nexus marketing its Emerphed RTU Syringes with an FDA-approved label that instructs healthcare providers on how to administer the product to treat hypotension, an act that allegedly constitutes performance of the claimed method (Compl. ¶¶59, 62-63).
- Willful Infringement: The complaint alleges willful infringement of all three patents. For the ’845 patent, willfulness is based on alleged pre-suit knowledge stemming from a declaratory judgment action Nexus filed on that patent on August 17, 2021 (Compl. ¶44). For the ’121 and ’710 patents, willfulness is based on alleged knowledge as of their respective issue dates (Compl. ¶¶55, 66).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of compositional proof: can Plaintiffs substantiate, through discovery and expert testing, their "information and belief" allegations that the accused product's formulation includes acetic acid, has an initial pH within the claimed 4.6-4.8 range, and meets the specific pH drift and impurity limitations required by the claims?
- A key legal question will be one of claim construction: how will the court construe the term "pH adjuster comprising acetic acid"? The case may turn on whether this requires acetic acid to be the sole or primary agent responsible for the pH adjustment and resulting stability, or if its mere presence is sufficient.
- A significant question for potential damages will be one of culpability: does Nexus's prior declaratory judgment action concerning the ’845 patent demonstrate that its subsequent alleged infringement was objectively reckless, thereby supporting the claim for willful infringement and potential enhanced damages?