DCT
1:22-cv-05683
Nexus Pharma LLC v. Endo Operations Ltd
Key Events
Amended Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Nexus Pharmaceuticals, LLC (Illinois)
- Defendants: Nevakar, Inc. (Delaware/New Jersey); Nevakar Injectables, Inc. (Delaware/New Jersey); Par Sterile Products, LLC (Delaware/Michigan); Par Pharmaceutical, Inc. (New York/New Jersey); Endo Ventures Unlimited Company (Ireland); and Operand Pharmaceuticals III Limited (Ireland)
- Plaintiff’s Counsel: Robinson Miller LLC; Marshall, Gerstein & Borun LLP
- Case Identification: 1:22-cv-05683, D.N.J., 08/10/2023
- Venue Allegations: Venue is based on Defendants having principal or regular and established places of business within the District of New Jersey, and on certain foreign Defendants being subject to suit in any judicial district.
- Core Dispute: Plaintiff alleges that Defendants’ ready-to-use prefilled syringe containing an ephedrine sulfate solution infringes three patents related to shelf-stable pharmaceutical compositions, methods of making such compositions, and methods of administering them.
- Technical Context: The technology relates to ready-to-use injectable drug formulations designed to eliminate the need for bedside dilution by clinicians, thereby reducing the risk of contamination and dosage errors in critical care settings like anesthesia.
- Key Procedural History: The operative pleading is a Second Amended Complaint filed in a consolidated action, suggesting a complex procedural history that may involve multiple related disputes or parties. The complaint also references prior litigation between related parties in the same district.
Case Timeline
| Date | Event |
|---|---|
| 2019-05-16 | Priority Date for ’369, ’752, and ’398 Patents |
| 2020-04-01 | Plaintiff's EMERPHED® NDA Approved (approx. date) |
| 2022-04-22 | FDA Approval of Defendants' Accused Product NDA Supplement |
| 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 |
| 2023-02-28 | Plaintiff's EMERPHED® Prefilled Syringe sNDA Approved |
| 2023-08-10 | Second 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”, Issued August 30, 2022
The Invention Explained
- Problem Addressed: The patent describes that all prior FDA-approved ephedrine sulfate formulations required a ten-fold dilution before administration, a step that is inconvenient, causes delays, and introduces a significant risk of microbial contamination and compounding errors in clinical settings (’369 Patent, col. 1:25-40).
- The Patented Solution: The invention is a method for making a shelf-stable, ready-to-use ephedrine sulfate composition that does not require dilution. The method involves combining specific concentrations of ephedrine sulfate, sodium chloride or dextrose, and water; filtering the solution; placing it into sanitized containers; sealing the containers; and ensuring the final product maintains a stable pH level for at least 12 months under specified storage conditions (’369 Patent, col. 16:16-41, Claim 1).
- Technical Importance: The claimed method produces a formulation that mitigates the risks of infection and dosage errors associated with bedside drug preparation for a critical medication used to treat hypotension during anesthesia (’369 Patent, col. 1:57-62).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶98).
- Essential elements of claim 1 include:
- Combining ephedrine sulfate, sodium chloride or dextrose, and water to form a batch solution with specific initial concentrations and no preservative.
- Optionally adjusting the initial pH level to between 4.5 and 7.
- Filtering the batch solution through a membrane filter.
- Sanitizing one or more containers.
- Placing not more than 20 mL of the solution into the sanitized containers.
- Sealing each container.
- Maintaining a pH level within 0.5 pH units of the initial pH during storage at 25°C for at least 12 months or at 40°C for at least 6 months.
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
The Invention Explained
- Problem Addressed: As with the '369 Patent, this patent addresses the clinical need for an ephedrine sulfate formulation that avoids the inconvenience and safety risks associated with mandatory pre-administration dilution (’752 Patent, col. 1:25-40).
- The Patented Solution: The invention is the pharmaceutical product itself: a packaged syringe containing a sterilized, ready-to-use ephedrine composition. The claims define the product by its specific formulation (5 mg/mL ephedrine sulfate, 9 mg/mL sodium chloride, no preservative, water, pH 4.5-7) and, critically, by its stability characteristics after prolonged storage under specified conditions (’752 Patent, Abstract, col. 11:4-12:12).
- Technical Importance: This invention provides clinicians with a commercially prepared, pre-packaged, and stable formulation of ephedrine sulfate at the correct concentration for direct administration, enhancing patient safety and speed of care (’752 Patent, col. 1:57-62).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶128).
- Essential elements of claim 1 include:
- A pharmaceutical product comprising a packaged syringe containing a sterilized ready-to-use ephedrine composition.
- The composition comprises 5 mg/mL ephedrine sulfate, 9 mg/mL sodium chloride, no preservative, water, and an initial pH of about 4.5 to 7.
- The composition, after storage for 12 months at 25°C or 6 months at 40°C, must have: a pH level within 0.5 pH 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.
Multi-Patent Capsule: 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
- Technology Synopsis: The ’398 Patent addresses the same clinical problem of dilution risk by claiming a method of using the ready-to-use product. The claimed invention is a method of administering ephedrine to a patient by removing a pre-filled syringe containing the specific, stable formulation from its packaging and injecting the composition directly into the subject without any dilution step (’398 Patent, Abstract, Claim 1).
- Asserted Claims: Independent claim 1 is asserted (Compl. ¶171).
- Accused Features: The complaint accuses Defendants of inducing infringement of this method patent. It alleges that Defendants’ marketing of their Prefilled Syringe Product with an FDA-approved package insert instructs and encourages healthcare providers to perform the claimed steps of administration (Compl. ¶¶168-169).
III. The Accused Instrumentality
- Product Identification: "Defendants' Prefilled Syringe Product," an ephedrine sulfate injection, 25 mg/5 mL (5 mg/mL), in a 5 mL single-dose prefilled syringe, approved under NDA No. 213994 (Compl. ¶¶48, 74).
- Functionality and Market Context: The accused product is alleged to be a sterile, shelf-stable, ready-to-use ephedrine sulfate composition intended for injection (Compl. ¶77). It reportedly contains 5 mg/mL ephedrine sulfate, 9 mg/mL sodium chloride, water with a pH between 4.5 and 7, and no preservative (Compl. ¶77). The complaint alleges the product is marketed and sold for use by healthcare professionals in surgical settings to treat hypotension (Compl. ¶¶80-81).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
11,426,369 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of making a shelf-stable, ready-to-use ephedrine sulfate composition, the method comprising: 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 or 5% dextrose, and no preservative; | Defendants allegedly manufacture their product by combining 5 mg/mL ephedrine sulfate, 9 mg/mL sodium chloride, and water, with no preservative. | ¶¶77, 98-99 | col. 16:21-26 |
| 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; | Defendants' product allegedly has a pH of between 4.5 and 7. | ¶¶77, 98-99 | col. 16:27-29 |
| filtering the batch solution through a membrane filter to obtain a filtered batch solution; | Defendants allegedly filter their product through a membrane to obtain a filtered batch solution. | ¶¶77, 98-99 | col. 16:30-31 |
| sanitizing one or more containers; | Defendants' product is allegedly contained in sanitized and sterilized sealed containers. | ¶¶77, 98-99 | col. 16:32 |
| placing not more than 20 mL of the filtered batch solution into one of the one or more sanitized containers...; | Defendants' product is a 5 mL solution placed into a prefilled syringe. | ¶¶74, 77, 98-99 | col. 16:33-35 |
| sealing each filled container to obtain sealed containers including a shelf-stable, ready-to-use ephedrine sulfate composition; and | Defendants' product is allegedly presented in a sealed 5 mL single-dose prefilled syringe. | ¶¶77, 98-99 | col. 16:36-38 |
| 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 at 25° C...for at least 12 months or during storage at 40° C...for at least 6 months. | Defendants' product is alleged to be shelf-stable for 6 and/or 12 months and stable at both ambient and accelerated conditions. | ¶¶77, 98-99 | col. 16:39-41 |
- Identified Points of Contention (’369 Patent):
- Scope Questions: A potential point of contention may be the interpretation of the "maintaining a pH level" limitation. A defendant could argue this is not a step they perform, but rather a property of the product after it leaves their control. The plaintiff may counter that this limitation is met by performing the preceding manufacturing steps which result in the claimed stability.
- Technical Questions: The complaint alleges, based on "reported information," that the accused product is shelf-stable for the claimed durations (Compl. ¶77). A key evidentiary question is what data supports that the product's pH actually remains "within 0.5 pH units of the initial pH level" after 12 months at 25°C, as specifically required by the claim.
11,464,752 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 comprising: | The accused product is a 5 mL single-dose prefilled syringe containing a sterilized, ready-to-use ephedrine sulfate composition. | ¶¶74, 77, 128-129 | col. 11:4-12 |
| a packaged concentration of ephedrine sulfate of 5 mg/mL, | The accused product allegedly contains 5 mg/mL ephedrine sulfate. | ¶¶77, 128-129 | col. 11:21-24 |
| 9 mg/mL sodium chloride, | The accused product allegedly contains 9 mg/mL sodium chloride. | ¶¶77, 128-129 | col. 11:8-12 |
| no preservative, | The accused product allegedly contains no preservative. | ¶¶77, 128-129 | col. 12:20-22 |
| water, and an initial pH level of about 4.5 to about 7; and | The accused product allegedly contains water and has a pH of between 4.5 and 7. | ¶¶77, 128-129 | col. 11:25-30 |
| having, after storage...for 12 months or...for 6 months: a pH level within 0.5 pH units of the initial pH level, an ephedrine sulfate concentration of at least 95% of the packaged concentration, and a bacterial endotoxin level not more than 7 EU/mg. | The accused product is alleged to be shelf-stable for 6 and/or 12 months under ambient and accelerated conditions. | ¶¶77, 128-129 | col. 11:40-12:12 |
- Identified Points of Contention (’752 Patent):
- Scope Questions: The dispute may center on the functional "having, after storage" limitation. The parties may dispute whether this requires literal testing of aged product or if stability can be inferred from manufacturing processes and quality control data.
- Technical Questions: The infringement allegation hinges on whether the accused product meets three distinct and quantitative stability metrics after storage. The complaint makes a general allegation of stability (Compl. ¶77), but a central evidentiary question will be whether the product actually maintains its pH within 0.5 units, its concentration at ≥95%, and its endotoxin level at ≤7 EU/mg over the claimed time periods.
V. Key Claim Terms for Construction
The Term: "having, after storage..." (’752 Patent, Claim 1)
Context and Importance: This term defines the patented product not just by its initial state but by its performance over time. Infringement requires proving the accused product possesses these specific stability characteristics. Practitioners may focus on this term because it is a functional limitation that is tested after the product is manufactured and sold, raising questions about the evidence required to prove infringement.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification's general statements about achieving stable compositions that do not require dilution could be cited to argue that any product designed to be shelf-stable in this manner falls within the claim's scope (’752 Patent, col. 1:41-44).
- Evidence for a Narrower Interpretation: The detailed stability data presented in the patent's examples (e.g., ’752 Patent, Tables 9, 10, and 11) could be used to argue that the claim is limited to products that demonstrate the specific stability profile shown in those tests.
The Term: "maintaining a pH level..." (’369 Patent, Claim 1)
Context and Importance: This term appears in a method-of-making claim but defines a property of the resulting product over time. Its construction is critical because it determines whether infringement occurs entirely during the manufacturing process or requires post-manufacturing conduct.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification describes a multi-step manufacturing method designed to yield a stable product, suggesting that "maintaining" is the intended and direct result of performing the preceding process steps, such as combining specific ingredients and sealing the container properly (’369 Patent, col. 16:16-41).
- Evidence for a Narrower Interpretation: A defendant may argue that the plain language "maintaining... during storage" refers to a period after manufacturing is complete and the product is no longer under the manufacturer's control, thereby arguing this step is not performed by the manufacturer.
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement of infringement for the ’398 method-of-use patent, asserting that Defendants’ FDA-approved package insert instructs and encourages healthcare providers to administer the accused product by removing it from packaging and injecting it without dilution, thereby performing the claimed steps (Compl. ¶¶168-169, 172). It also alleges inducement of contract manufacturers for the ’369 and ’752 patents (Compl. ¶¶99, 129).
- Willful Infringement: The complaint alleges that Defendants were aware of the patent applications that led to the Patents-in-Suit during their prosecution and have been aware of the issued patents since their respective issue dates (Compl. ¶¶89-90). It alleges that despite this knowledge, Defendants have continued their infringing activities (Compl. ¶90).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central evidentiary issue will be one of demonstrated stability: does the accused product actually meet the specific, quantitative stability metrics recited in the claims (e.g., maintaining pH within 0.5 units and concentration at ≥95% after 12 months at 25°C)? The case may turn on whether data from the product’s FDA approval file or subsequent testing confirms these precise performance characteristics.
- A key legal question will be one of claim scope for method steps: for the ’369 method-of-making patent, can the step of "maintaining a pH level... during storage" be satisfied by manufacturing a product that is inherently stable, or does it require active conduct by the defendant post-sale?
- The viability of the ’398 patent claim will depend on evidence of inducement: does the language of the accused product's FDA-approved label and marketing materials specifically instruct or encourage healthcare professionals to perform every step of the claimed method of administration, particularly injecting the composition "without diluting" it?