Nevakar Injectables Inc v. Baxter Healthcare Corp

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Nevakar Injectables, Inc. (Delaware) and Long Grove Pharmaceuticals, LLC (Delaware)
  • Defendant: Baxter Healthcare Corp. (Delaware)
  • Plaintiff’s Counsel: Richards, Layton & Finger, P.A.; Hahn Loeser & Parks LLP
• Case Identification: 1:25-cv-00301, D. Del., 03/11/2025
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because the defendant, Baxter Healthcare Corp., is a Delaware corporation and is therefore subject to personal jurisdiction in the district.
• Core Dispute: Plaintiffs allege that Defendant’s ready-to-administer norepinephrine bitartrate products infringe a patent covering stable, antioxidant-free norepinephrine compositions.
• Technical Context: The technology relates to pharmaceutical formulations of norepinephrine, a vasopressor used to treat acute hypotension, that are stable for long-term storage without requiring dilution or the use of potentially allergenic antioxidants like sulfites.
• Key Procedural History: Plaintiff Nevakar Injectables, Inc. is the owner of the patent-in-suit and has granted an exclusive license to co-plaintiff Long Grove Pharmaceuticals, LLC, which includes the right to sue for infringement. The complaint alleges that during patent prosecution, the Patent Examiner recognized that bitartrate originating from norepinephrine bitartrate can function as a metal ion chelator, a point that may be central to the infringement analysis.

Case Timeline

Date	Event
2017-01-30	'996 Patent Priority Date (Provisional App. 62/452,220)
2020-03-16	Baxter files NDA No. 214313 for its initial norepinephrine products
2021-01-15	FDA approves Baxter's NDA No. 214313
2021-09-23	Baxter begins offering for sale and selling its accused products
2023-05-04	Nevakar and Long Grove execute Exclusive License Agreement
2023-05-26	Baxter files supplemental NDA for additional product strength
2025-03-11	'996 Patent Issues
2025-03-11	Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 12,245,996 - Norepinephrine Compositions and Methods Therefor

• Patent Identification: U.S. Patent No. 12,245,996, "Norepinephrine Compositions and Methods Therefor," issued March 11, 2025.

The Invention Explained

• Problem Addressed: The patent’s background section describes challenges with then-existing norepinephrine formulations, which were typically sold as concentrates requiring dilution before administration. This process introduced risks of microbial contamination and calculation errors. Furthermore, these formulations often contained sulfites as antioxidants, which can cause severe allergic reactions in susceptible individuals (’996 Patent, col. 2:3-21).
• The Patented Solution: The invention is a ready-to-inject, sterile, aqueous norepinephrine composition that is stable without needing traditional antioxidants. The solution achieves stability through a combination of a specific, relatively narrow pH range (e.g., 3.7-5.0), the inclusion of a metal ion chelator, and a tonicity agent (’996 Patent, Abstract; col. 4:50-59). This approach is designed to reduce both degradation and isomerization of the active R-isomer of norepinephrine, allowing the product to be pre-packaged in a ready-to-use format.
• Technical Importance: The development of a stable, ready-to-inject, antioxidant-free formulation simplifies clinical workflow, reduces the potential for pharmacy compounding errors, and provides a safer alternative for patients with sulfite sensitivities (’996 Patent, col. 6:1-11).

Key Claims at a Glance

• The complaint provides Claim 1 as an example of an asserted independent claim (Compl. ¶22).
• The essential elements of independent Claim 1 are:
  • A sterile storage stable ready-to-inject norepinephrine composition, comprising:
  • an aqueous pharmaceutically acceptable solution containing norepinephrine, a tonicity agent, and a metal ion chelator;
  • wherein the norepinephrine is in an amount of equal or less than 100 µg/ml;
  • wherein the norepinephrine is present as an R-isomer in an amount of at least 90% of total norepinephrine;
  • wherein the aqueous solution comprises the metal ion chelator in an amount of between 1 µg/ml and 100 µg/ml, and wherein the metal ion chelator is a bicarboxylic acid;
  • wherein the tonicity agent is selected from the group consisting of a pharmaceutically acceptable salt, glycerol, a sugar alcohol, and a sugar; and
  • wherein the pH of the aqueous solution is in a range of between 3.7-5.0, and the composition is substantially antioxidant-free.
• The complaint alleges infringement of "one or more claims," reserving the right to assert others (Compl. ¶20).

III. The Accused Instrumentality

Product Identification

• The accused instrumentalities are "Baxter’s Norepinephrine Bitartrate Products," which are ready-to-administer formulations of norepinephrine bitartrate in 5% dextrose, sold in three strengths: 4 mg/250 mL (16 µg/ml), 8 mg/250 mL (32 µg/ml), and 16 mg/250 mL (64 µg/ml) (Compl. ¶¶15-16).

Functionality and Market Context

• The Baxter Products are FDA-approved for the restoration of blood pressure in adult patients with acute hypotensive states (Compl. ¶15). According to the complaint, the product label states they contain dextrose monohydrate, have a target pH of 3.7, use the R-configuration of norepinephrine, and are substantially free of an antioxidant (Compl. ¶17). These products are sold in 250 mL infusion bags, consistent with a ready-to-administer format (Compl. ¶15).
  No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

• '996 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A sterile storage stable ready-to-inject norepinephrine composition, comprising:	The Baxter Products are described as sterile storage stable ready-to-inject norepinephrine compositions.	¶26	col. 21:47-51
an aqueous pharmaceutically acceptable solution containing norepinephrine, a tonicity agent, and a metal ion chelator;	The Baxter Products are alleged to be aqueous solutions containing norepinephrine, a tonicity agent (dextrose), and a metal ion chelator (bitartrate).	¶27	col. 21:49-51
wherein the composition contains the norepinephrine in an amount of equal or less than 100 µg/ml;	The Baxter Products are sold in concentrations of 16, 32, and 64 µg/ml, all of which are less than 100 µg/ml.	¶28	col. 21:52-54
wherein the norepinephrine is present as an R-isomer in an amount of at least at least 90% of total norepinephrine;	The complaint alleges upon information and belief that the norepinephrine is present as an R-isomer in an amount of at least 90%.	¶28	col. 21:55-57
wherein the aqueous solution comprises the metal ion chelator ... and wherein the metal ion chelator is a bicarboxylic acid;	The complaint alleges that dissociated bitartrate anions from the norepinephrine bitartrate active ingredient function as the claimed metal ion chelator and are a bicarboxylic acid.	¶30	col. 4:65-col. 5:4
wherein the tonicity agent is selected from the group consisting of a pharmaceutically acceptable salt, glycerol, a sugar alcohol, and a sugar;	The Baxter Products are alleged to contain dextrose, which is a sugar and functions as a tonicity agent.	¶29	col. 21:61-64
wherein the pH of the aqueous solution is in a range of between 3.7-5.0, and wherein the composition is substantially antioxidant-free.	The complaint alleges the Baxter Products have a pH in the claimed range and are substantially antioxidant-free.	¶¶31, 32	col. 21:65-col. 22:2

• Identified Points of Contention:
  • Scope Questions: The central infringement dispute will likely concern the "metal ion chelator" limitation. The complaint’s theory is that the bitartrate counter-ion, which is part of the active pharmaceutical ingredient (API), satisfies this element (Compl. ¶30). A key question for the court will be one of claim scope: does the term "metal ion chelator," as used in the patent, require a distinct excipient added to the formulation for that purpose, or can it be read to cover a component of the API itself that serves this function? The complaint's reference to the prosecution history suggests this was a point of negotiation with the USPTO (Compl. ¶30).
  • Technical Questions: A related factual question is whether the bitartrate anion in the Baxter Products actually functions as a metal ion chelator to provide the claimed stability benefits. The defense may argue its primary function is as a salt-forming counter-ion and that any chelating effect is incidental and insufficient to meet the claim limitation as understood by a person of ordinary skill in the art.

V. Key Claim Terms for Construction

• The Term: "metal ion chelator"
• Context and Importance: The definition of this term appears to be dispositive. Plaintiffs' infringement theory depends on construing this term to include the bitartrate anion from the norepinephrine bitartrate API. If the court construes "metal ion chelator" to mean an ingredient separate from the API, added for the purpose of chelation, Plaintiffs' infringement case as currently pled could face significant challenges. Practitioners may focus on this term because the complaint explicitly relies on prosecution history to support its interpretation (Compl. ¶30).
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: Plaintiffs may argue that the claim language does not explicitly require the chelator to be a separately added ingredient, only that the "aqueous solution comprises" it. They could argue that if the bitartrate anion is present in the solution and performs the function of a bicarboxylic acid metal ion chelator, it meets the literal language of the claim, regardless of its origin.
  • Evidence for a Narrower Interpretation: The patent specification repeatedly provides examples of chelators, such as "EDTA, ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), and penta(carboxymethyl)diethylenetriamine (DTPA)" (’996 Patent, col. 6:57-60), which are all standard excipients added separately from the API. The description of preparing the composition includes steps of preparing an aqueous buffer that "also includes a chelating agent" and then dissolving norepinephrine into it, which suggests the chelator is a pre-existing, distinct component of the buffer vehicle (’996 Patent, col. 4:45-51). This could support an interpretation that the "metal ion chelator" must be a distinct excipient.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that Baxter indirectly infringes by "actively, knowingly, and intentionally aiding, abetting, directing, encouraging, or otherwise instructing third parties" to infringe (Compl. ¶25). However, the complaint does not plead specific facts to support this allegation, such as references to instructions on product labels or in user manuals that would induce infringing acts by end-users.
• Willful Infringement: The complaint alleges that Baxter's infringement is willful, entitling Plaintiffs to enhanced damages (Compl. ¶35). The complaint does not allege any facts supporting pre-suit knowledge of the patent, suggesting the willfulness claim is based on alleged continued infringement after the filing of the lawsuit.

VII. Analyst’s Conclusion: Key Questions for the Case

• A core issue will be one of claim interpretation: can the term "metal ion chelator", which the patent specification exemplifies with distinct excipients like EDTA, be construed to cover the bitartrate anion that is an integral part of the norepinephrine bitartrate active ingredient itself? The outcome of this question will likely determine the viability of the direct infringement claim.
• A central evidentiary question will be one of functionality: what evidence will be presented to establish that the bitartrate anion in Baxter's product performs the specific function of a "metal ion chelator" in a manner that contributes to the stability taught by the patent, as opposed to merely being present as a pharmaceutically acceptable counter-ion?
• A third question concerns prosecution history: the complaint invokes the patent’s prosecution history to support its infringement theory for the "metal ion chelator" limitation (Compl. ¶30). The specific arguments made to, and accepted by, the Patent Examiner will be heavily scrutinized to determine the scope of this critical claim term and whether prosecution history estoppel limits the range of equivalents.