DCT
2:23-cv-00299
Endo Ventures Ltd v. Nexus Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Endo Ventures Unlimited Company (Ireland), Operand Pharmaceuticals III Limited (Ireland), and Par Sterile Products, LLC (Delaware)
- Defendant: Nexus Pharmaceuticals, Inc. (Illinois)
- Plaintiff’s Counsel: Andrus Intellectual Property Law, LLP; Axinn, Veltrop & Harkrider LLP
- Case Identification: 2:23-cv-00299, E.D. Wis., 06/09/2023
- Venue Allegations: Venue is alleged to be proper based on Defendant Nexus having a regular and established place of business in the district, including a manufacturing facility.
- Core Dispute: Plaintiffs allege that Defendant’s ready-to-use ephedrine sulfate vial and syringe products infringe patents related to storage-stable pharmaceutical compositions and methods of their preparation.
- Technical Context: The technology provides a pre-diluted, pH-stable, ready-to-use ephedrine formulation, aiming to reduce medical errors and contamination risks associated with diluting concentrated ephedrine at the point of care.
- Key Procedural History: The complaint notes that Defendant Nexus previously filed a declaratory judgment action on August 17, 2021, concerning the ’845 patent, which subsequently settled; Plaintiffs cite this as evidence of Defendant's pre-suit knowledge of that patent.
Case Timeline
| Date | Event |
|---|---|
| 2020-01-22 | Priority Date for '845 and '121 Patents |
| 2020-04-17 | FDA Approval of Nexus's Emerphed RTU Vials |
| 2020-12-22 | '845 Patent Issue Date |
| 2021-08-17 | Nexus files Declaratory Judgment action re: '845 Patent |
| 2022-03-01 | Plaintiffs begin commercial marketing of Ephedrine RTU Vials |
| 2022-11-08 | '121 Patent Issue Date |
| 2023-03-01 | FDA Approval of Nexus's Emerphed RTU Syringes |
| 2023-06-09 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,869,845 - "Ephedrine Compositions and Methods" (Issued Dec. 22, 2020)
The Invention Explained
- Problem Addressed: The patent describes that prior FDA-approved ephedrine formulations were highly concentrated and required dilution before administration, a process that created risks of calculation errors, contamination, and overdose, particularly in emergency settings. Furthermore, these diluted solutions were not pH stable and were not recommended for storage. (’845 Patent, col. 2:46-68).
- The Patented Solution: The invention is a ready-to-use, storage-stable, sterile liquid composition of ephedrine that does not require dilution. It achieves stability through a specific combination of ephedrine concentration (about 5 mg/mL), sodium chloride, water, and an acetic acid pH adjuster that maintains the solution within a narrow pH range of 4.6 to 4.8. (’845 Patent, col. 6:1-15).
- Technical Importance: This approach provides a ready-to-administer formulation that was not previously commercially available, addressing known safety and efficiency issues in clinical settings. (Compl. ¶¶ 20-21).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1.
- Independent Claim 1 requires:
- A storage-stable, sterile ephedrine ready-to-use solution composition
- Comprising "about 5 mg/mL of ephedrine or a pharmaceutically acceptable salt thereof"
- Comprising "about 9 mg/mL of sodium chloride"
- Comprising "a pH adjuster comprising acetic acid"
- Comprising "water"
- Wherein the "initial adjusted pH" 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 specified conditions
- Wherein the composition contains "about 5% or less total impurities" after 6 months of storage at specified conditions
U.S. Patent No. 11,491,121 - "Ephedrine Compositions and Methods" (Issued Nov. 8, 2022)
The Invention Explained
- Problem Addressed: As a divisional of the application for the ’845 patent, the ’121 patent addresses the same technical problem of risks and instability associated with diluting concentrated ephedrine solutions. (’121 Patent, col. 2:46-68).
- The Patented Solution: This patent claims a method for preparing the storage-stable ephedrine composition. The method involves combining ephedrine and sodium chloride in an aqueous solution to specific concentrations and then adjusting the pH to the narrow 4.6 to 4.8 range using a solution that contains acetic acid. (’121 Patent, Abstract; col. 4:1-7).
- Technical Importance: By patenting the manufacturing method, the invention protects the process for creating the valuable ready-to-use composition described in the ’845 patent. (Compl. ¶¶ 20-21).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1.
- Independent Claim 1 requires:
- A method of preparing a storage-stable, sterile ephedrine ready-to-use solution composition
- Comprising the step of "combining" ephedrine (or its sulfate) and sodium chloride to concentrations of "about 5 mg/mL" and "about 9 mg/mL," respectively
- Comprising the step of "adjusting a pH" of the solution to a range of 4.6 to 4.8
- Wherein the pH is adjusted with a solution "containing acetic acid"
- Wherein the resulting composition has a "pH drift" of less than 0.5 after 6 months of storage
- Wherein the resulting composition contains "about 5% or less total impurities" after 6 months of storage
III. The Accused Instrumentality
- Product Identification: Defendant’s accused instrumentalities are its "Emerphed RTU Vials" and "Emerphed RTU Syringes" products. (Compl. ¶¶ 22, 24).
- Functionality and Market Context: The accused products are FDA-approved, ready-to-use ephedrine sulfate injections containing 5 mg/mL of the active ingredient, intended for treating hypotension during anesthesia. (Compl. ¶¶ 19, 22, 24). The complaint alleges these are "storage-stable, sterile ephedrine ready-to-use" products that require no dilution. (Compl. ¶34). A Nexus press release, referenced in the complaint, states that in 2020 Nexus was "the first manufacturer to launch an FDA-approved ephedrine sulfate injection in a ready-to-use vial." (Compl. ¶28, citing Ex. C). The complaint alleges the accused syringes are manufactured in Italy for Nexus and imported into the U.S. (Compl. ¶30).
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: | The accused syringes are alleged to contain a storage-stable, sterile ephedrine ready-to-use solution. | ¶34 | col. 6:58-65 |
| about 5 mg/mL of ephedrine or a pharmaceutically acceptable salt thereof; | The accused syringes are alleged to contain about 5 mg/mL of ephedrine or a salt thereof. | ¶35 | col. 6:1 |
| about 9 mg/mL of sodium chloride; | The accused syringes are alleged to contain about 9 mg/mL of sodium chloride. | ¶36 | col. 6:2 |
| a pH adjuster comprising acetic acid; and | The complaint alleges on information and belief that the accused syringes contain a pH adjuster comprising acetic acid, or that this limitation is met under the doctrine of equivalents. | ¶37 | col. 6:3 |
| water, | The accused syringes are alleged to contain water. | ¶36 | col. 6:4 |
| wherein the initial adjusted pH of the composition is in the range of 4.6 to 4.8; | The complaint alleges on information and belief that the accused syringes have an initial adjusted pH in the range of 4.6 to 4.8, or that this limitation is met under the doctrine of equivalents. | ¶38 | col. 6:4-6 |
| wherein the pH drift of the composition is less than 0.5 after storage for 6 months... | The complaint alleges on information and belief that the pH drift of the accused syringes is less than 0.5 after 6 months of storage, or that this limitation is met under the doctrine of equivalents. | ¶39 | col. 6:6-9 |
| wherein the composition contains about 5% or less total impurities after storage for 6 months... | The complaint alleges on information and belief that the accused syringes contain about 5% or less total impurities after 6 months of storage, or that this limitation is met under the doctrine of equivalents. | ¶40 | col. 6:9-13 |
'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: | The complaint alleges that the accused syringes are prepared by a method that results in such a composition. | ¶47 | col. 4:1-7 |
| 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; | The complaint alleges on information and belief that the accused syringes are prepared by combining these ingredients to the claimed concentrations, or that this limitation is met under the doctrine of equivalents. | ¶48 | col. 6:1-3 |
| adjusting a pH of the aqueous solution...to a range of 4.6 to 4.8...; | The complaint alleges on information and belief that the accused syringes are prepared by adjusting the pH to the claimed range, or that this limitation is met under the doctrine of equivalents. | ¶49 | col. 6:4-6 |
| wherein the pH is adjusted with a solution containing acetic acid; | The complaint alleges on information and belief that the pH adjustment step uses a solution containing acetic acid, or that this limitation is met under the doctrine of equivalents. | ¶49 | col. 6:3-4 |
| wherein a pH drift of the adjusted ephedrine composition is less than 0.5 after storage for 6 months... | The complaint alleges on information and belief that the resulting composition meets the claimed pH drift limitation, or that this limitation is met under the doctrine of equivalents. | ¶50 | col. 6:6-9 |
| wherein the composition contains about 5% or less total impurities after storage for 6 months... | The complaint alleges on information and belief that the resulting composition meets the claimed impurity limitation, or that this limitation is met under the doctrine of equivalents. | ¶51 | col. 6:9-13 |
Identified Points of Contention
- Evidentiary Questions: The complaint relies on "information and belief" and pleads infringement under the "doctrine of equivalents" for several key limitations, including the presence of acetic acid, the initial pH, the pH drift, and the impurity levels. (Compl. ¶¶ 37-40, 48-51). This suggests a central dispute will be whether discovery and testing can prove that the accused products literally meet these claim elements.
- Scope Questions: A likely point of dispute will be the interpretation of the term "about" as it modifies the concentration and impurity limitations. The extent to which this term broadens the claimed numerical ranges will be critical to the literal infringement analysis.
- Method Infringement: For the ’121 patent, proving that Defendant's manufacturing process, allegedly performed in Italy, meets each step of the claimed method may present an evidentiary challenge for Plaintiffs. (Compl. ¶30). The analysis may involve 35 U.S.C. § 271(g), which governs infringement by importation of a product made by a patented process.
V. Key Claim Terms for Construction
The Term: "a pH adjuster comprising acetic acid" (’845 Patent, Claim 1)
- Context and Importance: This ingredient is a core element of the claimed composition. The complaint's reliance on "information and belief" and the doctrine of equivalents for this limitation suggests that the exact pH adjuster used in the accused products is unknown to Plaintiffs and may not be acetic acid. (Compl. ¶37).
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification discusses pH adjusters more generally, listing various alkaline and acidic agents that can be used in pharmaceutical formulations, which a party might argue places the claimed term in a broader context. (’845 Patent, col. 11:18-36).
- Evidence for a Narrower Interpretation: The specification repeatedly highlights the surprising stability achieved when "the initial pH is adjusted with acetic acid." (’845 Patent, col. 6:28-30). The claims specifically recite "acetic acid," not a generic "acid" or "pH adjuster," suggesting the patentee intended to limit the claim to this specific substance, which provides a "higher buffer capacity at lower end of the pH" near its pKa. (’845 Patent, col. 11:59-65).
The Term: "about"
- Context and Importance: This term appears in the concentration limitations for ephedrine ("about 5 mg/mL") and sodium chloride ("about 9 mg/mL") as well as the impurity limitation ("about 5% or less"). (Compl. ¶33). Practitioners may focus on this term because its construction will define the literal boundaries of these numerical requirements.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification discloses broader concentration ranges, such as ephedrine from "4 mg/mL to 6 mg/mL" and sodium chloride from "1 mg/mL to 30 mg/mL," which could support a more flexible reading of "about." (’845 Patent, col. 2:22-23, 2:42-43).
- Evidence for a Narrower Interpretation: The claim for "initial adjusted pH" recites a hard numerical range of "4.6 to 4.8" without the word "about," which suggests the patentee knew how to claim a precise range when intended. (’845 Patent, col. 6:5-6). A party could argue this demonstrates that "about" should be given a narrow meaning, reflecting only minor variations consistent with standard measurement precision.
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement and contributory infringement for both patents, based on Defendant's alleged commercial manufacture, use, offers for sale, sales, and importation of the accused products. (Compl. ¶¶ 32, 41, 45, 52). The factual basis for intent is not extensively detailed beyond these commercial activities.
- Willful Infringement: The complaint alleges willful infringement for both patents. For the ’845 patent, willfulness is based on alleged pre-suit knowledge stemming from Defendant's own declaratory judgment action filed on August 17, 2021. (Compl. ¶43). For the ’121 patent, willfulness is based on alleged knowledge as of the patent's issue date of November 8, 2022. (Compl. ¶54).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of evidence and equivalence: can Plaintiffs prove through discovery that Defendant's product formulation and manufacturing process literally meet the claims, particularly the requirements for an "acetic acid" pH adjuster and the specific performance metrics for pH stability and impurities? If not, the case will turn on whether any differences are insubstantial enough to support infringement under the doctrine of equivalents.
- A second core issue will be one of definitional scope: how will the court construe the term "about"? The interpretation of this term will directly define the literal scope of the claimed concentration and impurity limitations and will be a critical factor in the infringement analysis.
- A key question for the ’121 patent will be one of process infringement: can Plaintiffs demonstrate that Defendant's manufacturing method, allegedly practiced in Italy, includes all steps of the claimed method? This may raise distinct evidentiary challenges related to extraterritorial conduct and the application of 35 U.S.C. § 271(g).