DCT
1:23-cv-02032
Nexus Pharma Inc v. Gland Pharma Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Nexus Pharmaceuticals, Inc. (Illinois)
- Defendant: Gland Pharma Limited (India)
- Plaintiff’s Counsel: STONE CONROY LLC; Rakoczy Molino Mazzochi Siwik LLP
- Case Identification: 1:23-cv-02032, D.N.J., 04/10/2023
- Venue Allegations: Venue is alleged to be proper because the Defendant is a foreign corporation subject to personal jurisdiction within the district. The complaint further notes that Defendant has previously litigated Hatch-Waxman patent disputes in the District of New Jersey without contesting jurisdiction.
- Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of EMERPHED® constitutes an act of infringement of four patents related to stable, ready-to-use ephedrine sulfate injection compositions.
- Technical Context: The technology concerns sterile injectable pharmaceutical formulations designed to treat hypotension during anesthesia, focusing on providing a product that is stable for long-term storage and does not require dilution by clinicians prior to administration.
- Key Procedural History: This patent infringement action was initiated under the Hatch-Waxman Act following Defendant's submission of ANDA No. 218211 to the FDA. Defendant provided a Paragraph IV Certification asserting that the patents-in-suit would not be infringed by its proposed generic product or are invalid. The patents-in-suit are listed in the FDA's "Approved Drug Products with Therapeutic Equivalence Evaluations" (the "Orange Book") as covering Plaintiff's EMERPHED® product.
Case Timeline
| Date | Event |
|---|---|
| 2019-05-16 | Priority Date for ’278, ’400, ’436, and ’369 Patents |
| 2020-04-21 | FDA Approval of EMERPHED® New Drug Application |
| 2021-08-17 | U.S. Patent No. 11,090,278 Issues |
| 2022-02-08 | U.S. Patent No. 11,241,400 Issues |
| 2022-08-30 | U.S. Patent No. 11,426,369 Issues |
| 2022-10-25 | U.S. Patent No. 11,478,436 Issues |
| 2023-03-01 | Date of Gland Pharma’s Notice Letter to Nexus |
| 2023-04-10 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,090,278 - “Compositions comprising ephedrine or an ephedrine salt and methods of making and using same,” issued August 17, 2021
The Invention Explained
- Problem Addressed: The patent describes that all prior FDA-approved formulations of ephedrine sulfate required a ten-fold dilution before administration to a patient. This process is described as inconvenient, a source of potential clinical error, a delay to therapeutic intervention, and a significant risk of microbial contamination of an otherwise sterile product (’278 Patent, col. 1:15-30). Furthermore, ready-to-use preparations were not known to be stable for extended periods, with shelf lives of 60 days or less (’278 Patent, col. 1:57-61).
- The Patented Solution: The invention provides a ready-to-use, premixed pharmaceutical composition of ephedrine sulfate that does not require reconstitution or dilution prior to administration (’278 Patent, Abstract; col. 2:50-61). The formulation is designed to remain stable and active after prolonged storage, thereby solving the problems of inconvenience, error, and contamination associated with bedside dilution (’278 Patent, col. 2:50-61). The composition generally consists of ephedrine sulfate, an isotonic agent such as sodium chloride, and water, and is notably free of preservatives (’278 Patent, col. 12:16-19).
- Technical Importance: The invention provides clinicians with a formulation of a critical care drug that can be administered immediately, which may reduce the risk of medication errors and microbial contamination in high-pressure environments such as operating rooms (’278 Patent, col. 1:20-25).
Key Claims at a Glance
The complaint does not identify specific claims asserted against Defendant, alleging infringement of "one or more claims" (Compl. ¶51). Claim 1 is the first independent claim and is representative of the patent's scope.
- Independent Claim 1: A method of administering ephedrine sulfate consisting essentially of:
- Drawing a shelf-stable ready-to-use ephedrine sulfate composition from a sterile premixed pharmaceutical product into a syringe;
- Injecting the composition into the subject using the syringe;
- Wherein the composition consists essentially of: 5 mg/mL +/-5% ephedrine sulfate, 9 mg/mL sodium chloride, no preservative, and water; and
- Wherein the composition is prepared by a process of combining the ingredients, placing the solution into depyrogenated glass vials, sealing the vials, and terminally sterilizing the sealed vials.
The complaint reserves the right to assert infringement of additional claims, which may include dependent claims (Compl. ¶51).
U.S. Patent No. 11,241,400 - “Compositions comprising ephedrine or an ephedrine salt and methods of making and using same,” issued February 8, 2022
The Invention Explained
- Problem Addressed: As with the related ’278 Patent, this patent addresses the clinical drawbacks of ephedrine sulfate formulations that require dilution, citing risks of error, contamination, and treatment delays (’400 Patent, col. 1:21-38). The patent also notes that prior ready-to-use ephedrine formulations had limited shelf stability (’400 Patent, col. 1:61-67).
- The Patented Solution: The invention discloses a ready-to-use packaged pharmaceutical composition containing ephedrine or a salt thereof that overcomes the stability issues of prior art formulations (’400 Patent, Abstract; col. 2:56-66). The key feature is the composition's demonstrated long-term stability, specifically its ability to maintain its concentration of the active ingredient over an extended period without preservatives (’400 Patent, col. 5:6-19).
- Technical Importance: By providing a verifiably stable, ready-to-use formulation, this invention offers a safer and more efficient alternative for administering ephedrine sulfate in clinical settings where hypotension must be treated promptly (’400 Patent, col. 1:21-28).
Key Claims at a Glance
The complaint does not identify specific claims asserted, alleging infringement of "one or more claims" (Compl. ¶63). Claim 1 is the first independent claim.
- Independent Claim 1:
- A ready-to-use packaged pharmaceutical composition comprising ephedrine or a pharmaceutically acceptable salt thereof;
- Wherein the pharmaceutical composition exhibits no more than about 5% decrease in a concentration of the ephedrine or pharmaceutically acceptable salt thereof upon storage for at least 24 months.
The complaint reserves the right to assert infringement of additional claims (Compl. ¶63).
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
- Technology Synopsis: This patent, part of the same family, is also directed to solving the technical problems of contamination, dosing errors, and instability associated with diluted ephedrine sulfate injections (’436 Patent, Abstract; col. 1:21-46). The patented solution is a ready-to-use, preservative-free ephedrine sulfate formulation that is stable for long-term storage and can be administered without prior dilution (’436 Patent, col. 2:50-61).
- Asserted Claims: The complaint does not specify which claims are asserted (Compl. ¶75). The patent includes independent claims 1 and 19.
- Accused Features: The Gland ANDA Product is accused of infringing by being a ready-to-use ephedrine sulfate injection that allegedly has the same formulation and stability characteristics as the patented invention (Compl. ¶35-39, 44).
U.S. Patent No. 11,426,369 - “Compositions Comprising Ephedrine or and Ephedrine Salt and Methods of Making and Using Same,” issued August 30, 2022
- Technology Synopsis: This patent also addresses the need for improved formulations of ephedrine sulfate by providing a ready-to-use, premixed composition that is stable over long-term storage (’369 Patent, Abstract; col. 1:21-46). The invention aims to eliminate the risks and inconveniences associated with the clinical practice of diluting concentrated ephedrine sulfate prior to injection (’369 Patent, col. 2:55-65).
- Asserted Claims: The complaint does not specify which claims are asserted (Compl. ¶87). The patent includes independent claim 1.
- Accused Features: The Gland ANDA Product, a ready-to-use ephedrine sulfate injection, is alleged to be the same composition, intended for the same use, and possessing the same stability as the patented invention (Compl. ¶35-39, 44).
III. The Accused Instrumentality
- Product Identification: The accused instrumentality is "Gland's ANDA Product," a generic Ephedrine Sulfate Injection USP, 50mg/10mL (5 mg/mL) in single dose vials, for which Defendant Gland Pharma Limited submitted Abbreviated New Drug Application (ANDA) No. 218211 to the FDA (Compl. ¶33, ¶35).
- Functionality and Market Context: The complaint alleges Gland's ANDA Product is a ready-to-use, pre-mixed composition intended for the treatment of clinically important hypotension occurring in the setting of anesthesia (Compl. ¶37, ¶44). The formulation is alleged to contain ephedrine sulfate, sodium chloride, and water in amounts equivalent to Plaintiff's EMERPHED® product and does not contain a preservative (Compl. ¶38). The proposed labeling for Gland's product allegedly instructs administration to patients by drawing the composition into a syringe and injecting it without dilution (Compl. ¶46). As a generic version of EMERPHED®, the product is positioned to compete directly with Plaintiff's commercial embodiment of the patents-in-suit (Compl. ¶21, ¶35).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
As the complaint does not specify which claims of the patents-in-suit are asserted, the following tables summarize the infringement allegations based on representative independent claims.
- 11,090,278 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of administering ephedrine sulfate to a subject... [by] drawing a shelf-stable ready-to-use ephedrine sulfate composition... into a syringe; and injecting the composition into the subject... | Defendant's proposed labeling allegedly instructs and promotes administration to patients by drawing the composition into a syringe and injecting it without dilution. | ¶46 | col. 14:55-62 |
| wherein the shelf-stable ready-to-use ephedrine sulfate composition consists essentially of: 5 mg/mL+/-5% ephedrine sulfate; | Gland's ANDA Product is an ephedrine sulfate injection, 50mg/10mL (5 mg/mL). | ¶35 | col. 11:18-22 |
| 9 mg/mL sodium chloride; | Gland's ANDA Product allegedly contains sodium chloride... in the same or equivalent amounts as EMERPHED®. | ¶38 | col. 11:18-22 |
| no preservative; and | Gland's ANDA Product allegedly does not contain a preservative. | ¶38 | col. 12:16-19 |
| water | Gland's ANDA Product allegedly contains water. | ¶38 | col. 11:18-22 |
- 11,241,400 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A ready-to-use packaged pharmaceutical composition... | Gland's ANDA product is alleged to be a ready to use pre-mixed composition. | ¶37 | col. 2:50-53 |
| comprising ephedrine or a pharmaceutically acceptable salt thereof | The active ingredient of Gland's ANDA product is alleged to be ephedrine sulfate. | ¶36 | col. 3:62-63 |
| wherein the pharmaceutical composition exhibits no more than about 5% decrease in a concentration of the ephedrine... upon storage for at least 24 months. | Gland's ANDA product is alleged to be a generic version of EMERPHED®, which embodies the patented technology, and to feature the same or equivalent chemical properties and storage conditions, implying it will meet the same stability profile. | ¶35, ¶37, ¶39 | col. 5:6-19 |
- Identified Points of Contention:
- Scope Questions: For the ’278 Patent, a potential dispute may arise over the claim term "consisting essentially of." The question will be whether Gland's formulation contains any unlisted ingredients and, if so, whether those ingredients materially affect the basic and novel properties of the ready-to-use, preservative-free composition.
- Technical Questions: For the ’400 Patent, a primary question will be evidentiary: What proof exists within Gland's ANDA submission to demonstrate that its product will meet the specific, quantitative stability limitation of "no more than about 5% decrease... upon storage for at least 24 months"? The litigation may explore whether being a bioequivalent generic that is stored under equivalent conditions is sufficient to meet this claim element.
V. Key Claim Terms for Construction
The Term: "shelf-stable" (’278 Patent)
- Context and Importance: This term is central to the asserted invention, as the primary technical challenge addressed was the limited stability of prior ready-to-use ephedrine formulations. The construction of this term will be critical for determining whether Gland's product, as described in its ANDA, infringes.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification states the invention provides a formulation that "remains stable and active after prolonged storage," suggesting a functional, non-specific definition (’278 Patent, col. 2:59-61). Various passages describe stability over different time periods (e.g., at least 12 months, at least 24 months), which could support a flexible interpretation not tied to a single duration (’278 Patent, col. 5:6-19).
- Evidence for a Narrower Interpretation: The patent includes detailed examples with specific stability data measured over 24 months at 25°C (’278 Patent, Example 2; Tables 7-13). This data could be used to argue that "shelf-stable" should be construed more narrowly to mean stable under those demonstrated conditions and for that duration.
The Term: "consisting essentially of" (’278 Patent)
- Context and Importance: This transitional phrase defines the boundary of the claimed composition. It permits the presence of unlisted components so long as they do not materially alter the basic and novel properties of the invention. The dispute will center on what those properties are and whether any excipients in Gland's product affect them.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation (favoring infringement): The specification emphasizes that the formulation solves the problem of instability in ready-to-use preparations without needing preservatives or chelating agents (’278 Patent, col. 10:41-57). This suggests the "basic and novel properties" are stability and sterility in a preservative-free, ready-to-use format.
- Evidence for a Narrower Interpretation (favoring non-infringement): A defendant may argue that the "basic and novel properties" are more specific, such as achieving stability within a particular pH range or osmolality. They could then contend that an unlisted component in their formulation, even if minor, affects one of these more specific properties, thereby taking the product outside the claim's scope.
VI. Other Allegations
- Indirect Infringement: The complaint alleges induced infringement, stating that Gland's proposed product labeling instructs and encourages medical professionals to perform the steps of the patented method claims, such as by directing them to draw the ready-to-use composition into a syringe and inject it without dilution (Compl. ¶46, ¶52, ¶53). Contributory infringement is also alleged on the basis that Gland's product is especially made for an infringing use and is not suitable for a substantial non-infringing use (Compl. ¶54).
- Willful Infringement: Willfulness is alleged for all four patents-in-suit. The complaint asserts that Gland has acted with "full knowledge" of the patents and "without a reasonable basis for believing that it would not be liable for infringing" (Compl. ¶57, ¶69, ¶81, ¶93). This allegation is based on Gland's submission of a Paragraph IV certification, which serves as evidence of Gland's pre-suit knowledge of the patents.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of evidentiary proof: In this pre-launch ANDA litigation, can Nexus establish by a preponderance of the evidence that Gland's proposed generic product, if manufactured and sold, would necessarily infringe the asserted claims? This question is particularly salient for claim limitations reciting specific, long-term stability performance (e.g., "no more than about 5% decrease... upon storage for at least 24 months"), where infringement may depend on inferences drawn from the ANDA filing rather than direct testing of the accused product.
- A second central issue will be one of claim scope: The litigation will likely focus on construing the term "consisting essentially of" as used in method claims. The court's determination of the "basic and novel properties" of the preservative-free, ready-to-use composition will be dispositive for whether any minor formulation differences in Gland's product are sufficient to place it outside the scope of those claims.