DCT
1:23-cv-01248
Nexus Pharma Inc v. Somerset Pharma LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Nexus Pharmaceuticals, Inc. (Illinois)
- Defendant: Somerset Therapeutics, LLC (Delaware/Florida); Somerset Pharma, LLC (Delaware/New Jersey)
- Plaintiff’s Counsel: ROBINSON MILLER LLC
- Case Identification: 3:23-cv-01248, D.N.J., 04/14/2023
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendants submitted their Abbreviated New Drug Application (ANDA) from their New Jersey place of business and maintain a regular and established place of business in the state.
- Core Dispute: Plaintiff alleges that Defendants' submission of an ANDA to the FDA seeking approval to market a generic version of Plaintiff's EMERPHED® product constitutes an act of infringement of two patents covering ready-to-use ephedrine sulfate formulations.
- Technical Context: The technology concerns sterile, ready-to-use injectable pharmaceutical compositions of ephedrine sulfate for treating clinically significant hypotension, particularly in the setting of anesthesia.
- Key Procedural History: This is a Hatch-Waxman Act lawsuit initiated in response to Defendants' filing of ANDA No. 218113 with a Paragraph IV certification. This certification asserts that the patents-in-suit, which are listed in the FDA's "Orange Book" for EMERPHED®, are either invalid or will not be infringed by Defendants' proposed generic product.
Case Timeline
| Date | Event |
|---|---|
| 2019-05-16 | Priority Date for ’436 and ’369 Patents |
| 2020-04-21 | FDA approves EMERPHED® New Drug Application |
| 2022-08-30 | U.S. Patent No. 11,426,369 issues |
| 2022-10-25 | U.S. Patent No. 11,478,436 issues |
| 2023-01-19 | Somerset sends first notice letter to Nexus |
| 2023-03-14 | Somerset sends second notice letter to Nexus |
| 2023-04-14 | Nexus files First Amended Complaint |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,478,436 - "Compositions Comprising Ephedrine or an Ephedrine Salt and Methods of Making and Using Same"
- Issued: October 25, 2022
The Invention Explained
- Problem Addressed: The patent describes that prior FDA-approved ephedrine formulations required a ten-fold dilution before being administered to a patient. This dilution step is described as inconvenient, a cause of delays in therapeutic intervention, and a significant source of potential dosing errors and microbial contamination in a clinical setting (ʼ436 Patent, col. 1:24-42).
- The Patented Solution: The invention is a ready-to-use, premixed, and shelf-stable pharmaceutical composition of ephedrine sulfate that does not require dilution prior to administration. The solution combines ephedrine sulfate with an isotonic agent, such as sodium chloride, in water to provide a sterile, stable formulation at a clinically appropriate concentration (e.g., 5 mg/mL), thereby eliminating the risks associated with bedside dilution (ʼ436 Patent, Abstract; col. 2:10-23).
- Technical Importance: This approach is intended to enhance patient safety and clinical efficiency by providing a standardized, ready-to-administer product, which reduces the opportunity for medication preparation errors and contamination associated with compounding or diluting concentrated drugs (ʼ436 Patent, col. 1:43-52).
Key Claims at a Glance
- The complaint does not identify specific claims, but the infringement theories point toward method of administration claims, such as independent claim 1.
- Independent Claim 1 elements include:
- A method of administering ephedrine sulfate to a subject having or at risk of hypotension.
- Drawing a sterile, shelf-stable, ready-to-use pharmaceutical product from a sealed container, where the product comprises 5 mg/mL ephedrine sulfate, 9 mg/mL sodium chloride or 5% dextrose, and no preservative.
- Not diluting the product after drawing it.
- Injecting the product into the subject.
- Wherein the product is prepared by a specific multi-step process.
- The complaint reserves the right to assert additional claims (Compl. ¶46).
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: As with its related patent, the ’369 Patent addresses the clinical risks and inefficiencies associated with existing ephedrine formulations that must be diluted before use, citing the potential for contamination and incorrect dosing (ʼ369 Patent, col. 1:24-42).
- The Patented Solution: The patent describes methods of making a ready-to-use, shelf-stable ephedrine sulfate formulation. The solution involves combining specific concentrations of ephedrine sulfate and an isotonic agent in water, filtering and placing the solution into sanitized containers, and sealing them to maintain sterility and stability over time, thus providing a product that is immediately ready for clinical use (ʼ369 Patent, Abstract; col. 16:11-30).
- Technical Importance: The invention provides a manufacturing method for a product intended to reduce the incidence of drug preparation errors and microbial contamination, a known problem in fast-paced medical environments where concentrated drugs are frequently diluted (ʼ369 Patent, col. 1:31-42).
Key Claims at a Glance
- The complaint does not identify specific claims, but the allegations of infringement by manufacture point toward method of making claims, such as independent claim 1.
- Independent Claim 1 elements include:
- A method of making a shelf-stable, ready-to-use ephedrine sulfate composition.
- Combining ephedrine sulfate, sodium chloride or dextrose, and water to form a batch solution with specific concentrations and no preservative.
- Optionally adjusting the pH.
- Filtering the batch solution.
- Sanitizing containers.
- Placing the filtered solution into the sanitized containers.
- Sealing the filled containers.
- Maintaining a stable pH level during storage.
- The complaint reserves the right to assert additional claims (Compl. ¶58).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is "Somerset’s ANDA Product," a generic Ephedrine Sulfate Injection, USP, 50mg/10mL (5 mg/mL) in single-dose vials, for which Defendants seek FDA approval via ANDA No. 218113 (Compl. ¶¶28-29).
Functionality and Market Context
- The complaint alleges that the ANDA product is a generic version of Nexus’s EMERPHED® product and contains the same or equivalent active and inactive ingredients (ephedrine sulfate, sodium chloride, water) in the same or equivalent amounts (Compl. ¶¶30, 33).
- It is alleged to be a ready-to-use, premixed composition that does not contain a preservative (Compl. ¶¶32, 33).
- The proposed labeling for the ANDA product allegedly recommends its use for treating clinically important hypotension and instructs administration by drawing the composition into a syringe and injecting it "without dilution" (Compl. ¶¶39, 41).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’436 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| drawing a sterile, shelf-stable ready-to-use ephedrine sulfate pharmaceutical product comprising 5 mg/mL ephedrine sulfate...and no preservative from a sealed container into a syringe; | The proposed labeling for Somerset's ANDA product is alleged to instruct users to draw the composition, which allegedly contains 5 mg/mL ephedrine sulfate and no preservative, into a syringe for administration. | ¶28, ¶33, ¶41 | col. 47:7-14 |
| not diluting the sterile, shelf-stable ready-to-use ephedrine sulfate pharmaceutical product after the step of drawing... | The proposed labeling allegedly instructs injecting the composition "without dilution." | ¶41 | col. 47:15-19 |
| injecting the sterile, shelf-stable ready-to-use ephedrine sulfate pharmaceutical product into the subject using the syringe... | The proposed labeling allegedly instructs and promotes the injection of the composition into a patient to treat hypotension. | ¶40, ¶41 | col. 47:20-23 |
’369 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| combining ephedrine sulfate, sodium chloride...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; | Somerset's ANDA product is alleged to be manufactured using equivalent methods as EMERPHED® and to contain ephedrine sulfate and sodium chloride in the same amounts, with no preservative. | ¶33, ¶35 | col. 46:2-9 |
| filtering the batch solution through a membrane filter to obtain a filtered batch solution; | The ANDA product is alleged to be manufactured using methods equivalent to those for EMERPHED® and to be sterilized, which the patent teaches involves filtration. | ¶35, ¶37 | col. 46:10-11 |
| placing not more than 20 mL of the filtered batch solution into one of the one or more sanitized containers... | The ANDA product is supplied in 10 mL single-dose vials, necessarily requiring the solution to be placed into containers. | ¶28, ¶36 | col. 46:14-17 |
| sealing each filled container to obtain sealed containers... | The ANDA product is supplied as a sterile product in sealed single-dose vials. | ¶19, ¶28, ¶36 | col. 46:18-20 |
Identified Points of Contention
- Evidentiary Questions: The complaint relies heavily on "information and belief." A central issue will be whether discovery confirms that Somerset's manufacturing process and final product specifications meet every limitation of the asserted claims. The infringement case for the ’369 patent, in particular, hinges entirely on evidence of Somerset's actual manufacturing process.
- Technical Questions: The method claim of the ’436 patent requires that the administered product be "prepared by a process comprising" a specific series of steps. A key question for the court will be whether Nexus can prove that Somerset’s ANDA product is made by that recited process, as direct infringement of that claim requires satisfying the process limitations.
V. Key Claim Terms for Construction
The Term: "shelf-stable"
- Context and Importance: This term appears in the asserted claims and is central to the invention's purported solution to the problems with prior art formulations. The definition of "shelf-stable" will be critical for both infringement (does the accused product meet the definition?) and validity (does the prior art teach a "shelf-stable" ready-to-use formulation?).
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides functional definitions, stating a composition may be considered stable if it comprises at least 70%, 80%, or 90% of the initial amount of the active ingredient after storage for a defined period, such as 12 or 24 months (e.g., ’436 Patent, col. 6:35-48).
- Evidence for a Narrower Interpretation: The patent's detailed examples show specific stability results under defined conditions (e.g., 25°C/60% RH). A party could argue these examples limit the term to compositions that exhibit the high degree of stability shown in those tests, such as retaining over 99% of the label claim after 24 months (’436 Patent, Table 10).
The Term: "no preservative"
- Context and Importance: This negative limitation is a key feature of the claimed composition, distinguishing it from formulations that achieve stability through chemical preservatives. Its construction is important for defining the boundary of the claim.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party may argue the term should be given its plain and ordinary meaning: the absence of any ingredient added for the purpose of preventing microbial growth.
- Evidence for a Narrower Interpretation: The specification provides an exemplary list of what the invention does not include, naming specific preservatives like "benzyl alcohol, chlorobutanol," parabens, and phenols (’436 Patent, col. 9:41-50). A party could argue the term is defined by this list or that an unlisted compound with incidental antimicrobial properties would not be excluded.
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement of the method claims, asserting that the proposed labeling for Somerset's ANDA product instructs and encourages medical professionals to administer the product in a manner that directly infringes (e.g., by drawing from the vial and injecting without dilution) (Compl. ¶¶40-41, 47). It also pleads contributory infringement, alleging the product is especially made for an infringing use and has no substantial non-infringing use (Compl. ¶49, ¶61).
- Willful Infringement: Willfulness is alleged based on Defendants having "full knowledge" of the patents-in-suit prior to the litigation, as evidenced by their filing of a Paragraph IV certification, and allegedly proceeding "without a reasonable basis for believing" they would not be liable for infringement (Compl. ¶52, ¶64).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of factual proof: As the complaint is based on "information and belief," a primary focus of the litigation will be on whether discovery reveals that Somerset’s actual manufacturing process and final product specifications meet every limitation of the asserted process and method claims.
- A key question for the court will be obviousness: The ultimate outcome will likely depend on whether it was obvious to a person of ordinary skill in the pharmaceutical arts at the time of the invention to create a preservative-free, ready-to-use, 5 mg/mL ephedrine sulfate formulation with the claimed long-term stability, or whether this achievement was unexpected and non-obvious.
- A dispositive issue may be one of process equivalence: For the method claims that recite specific manufacturing steps, a key dispute will be whether Somerset's process is identical to or legally equivalent to the claimed process, or whether Somerset has successfully designed around these specific limitations.