DCT
2:24-cv-05674
Fresenius Kabi USA LLC v. Accord Healthcare Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Fresenius Kabi USA, LLC (Delaware)
- Defendant: Accord Healthcare Inc. (North Carolina)
- Plaintiff’s Counsel: ArentFox Schiff LLP
- Case Identification: 2:24-cv-05674, D.N.J., 04/26/2024
- Venue Allegations: Venue is alleged to be proper based on Defendant's registration to do business in New Jersey, its regular and established place of business in the district, and its consent to jurisdiction and venue for this action.
- Core Dispute: Plaintiff alleges that Defendant’s filing of a New Drug Application for a generic levothyroxine sodium injection constitutes an act of infringement of two patents covering stable, liquid formulations of the drug.
- Technical Context: The patents relate to ready-to-use, injectable liquid formulations of levothyroxine, a thyroid hormone replacement therapy, designed to overcome the stability and contamination issues associated with traditional lyophilized (powder) forms that require reconstitution.
- Key Procedural History: This is a Hatch-Waxman action triggered by Defendant’s submission of New Drug Application (NDA) No. 219224, which included a Paragraph IV certification asserting that Plaintiff's patents are invalid, unenforceable, and/or will not be infringed. The parties previously litigated in the same district over a different generic levothyroxine sodium product.
Case Timeline
| Date | Event |
|---|---|
| 2016-12-01 | Earliest Priority Date for ’669 and ’190 Patents |
| 2019-04-11 | FDA approves Fresenius Kabi's NDA for Levothyroxine Sodium injection |
| 2019-09-03 | U.S. Patent No. 10,398,669 issues |
| 2021-10-05 | U.S. Patent No. 11,135,190 issues |
| 2024-03-14 | Accord sends Notice Letter regarding its NDA |
| 2024-04-26 | Complaint filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,398,669, “Levothyroxine Liquid Formulations,” issued September 3, 2019
The Invention Explained
- Problem Addressed: The patent describes the challenges with conventional levothyroxine sodium formulations, which are typically sold as lyophilized powders that must be reconstituted by healthcare practitioners before use. This process introduces risks of contamination and is inconvenient, and the resulting solutions have limited stability, requiring use within hours (’669 Patent, col. 1:47-53). While aqueous solutions are an alternative, levothyroxine is known to degrade in water, even at a basic pH where it is more stable (’669 Patent, col. 1:54-65). The patent identifies a need for a "ready-to-use injectable formulation...that exhibits storage stability" (’669 Patent, col. 2:1-4).
- The Patented Solution: The invention is a stable, ready-to-use liquid formulation that combines levothyroxine with a specific stabilizing agent, tromethamine, in water. The formulation is defined by its ability to maintain at least 95% of its initial drug concentration after extended storage periods at both room temperature (12 months) and accelerated conditions (2 months at 40°C) (’669 Patent, Claim 1, col. 16:1-12). The patent posits that tromethamine provides a stabilizing effect that is "unrelated to buffering of the formulation" (’669 Patent, col. 5:30-34).
- Technical Importance: This technology aims to provide a safer, more convenient, and more stable alternative to existing levothyroxine treatments, particularly for urgent care settings like myxedema coma where parenteral administration is necessary (’669 Patent, col. 1:16-22).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶37).
- Independent Claim 1 requires:
- A liquid formulation comprising levothyroxine or a pharmaceutically acceptable salt thereof;
- A stabilizing agent comprising tromethamine;
- Not more than 2% liothyronine (T3);
- Water;
- Wherein the formulation retains at least about 95% of the initial concentration of levothyroxine after storage for 12 months at 25±2 °C; and
- Wherein the formulation retains at least about 95% of the initial concentration of levothyroxine after storage for 2 months at 40±2 °C.
- The complaint alleges infringement of "each claim" of the patent (Compl. ¶34).
U.S. Patent No. 11,135,190, “Levothyroxine Liquid Formulations,” issued October 5, 2021
The Invention Explained
- Problem Addressed: As a continuation of the application leading to the ’669 Patent, this patent addresses the same technical problem: the need for a stable, ready-to-use, injectable liquid formulation of levothyroxine to avoid the drawbacks of reconstituted powders (’190 Patent, col. 2:3-6).
- The Patented Solution: The invention is a "pharmaceutical product" containing a liquid formulation of levothyroxine stabilized by an amine selected from a specific list (a Markush group) that includes tromethamine and several other related compounds (’190 Patent, Claim 1, col. 33:48-55). The product is defined by functional stability requirements, claiming a formulation that retains at least 95% of its initial drug concentration after two months at 40°C and after at least 12 months at room temperature (’190 Patent, Claim 1, col. 33:55 - col. 34:2).
- Technical Importance: This patent broadens the scope of the potential stabilizing agents beyond just tromethamine while retaining the core concept of achieving specific, long-term stability in a liquid, ready-to-use format (’190 Patent, col. 4:15-22).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶49-50).
- Independent Claim 1 requires:
- A pharmaceutical product comprising a liquid formulation;
- The formulation comprises levothyroxine or a pharmaceutically acceptable salt thereof;
- A stabilizing agent comprising an amine selected from a Markush group including tromethamine, bis(2-hydroxyethyl)-imino-tris(hydroxymethyl)methane, monoethanolamine, triethanolamine, and others;
- Water;
- Wherein the formulation retains at least 95% of the initial concentration of levothyroxine after storage for two months at 40°C; and
- Wherein the formulation retains at least 95% of the initial concentration of levothyroxine after storage for at least 12 months at room temperature.
- The complaint alleges infringement of "each claim" of the patent (Compl. ¶47).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is "Accord's NDA Product," a proposed levothyroxine sodium injection at a strength of 100 mcg/mL, for which Accord Healthcare Inc. filed New Drug Application (NDA) No. 219224 (Compl. ¶2, ¶22, ¶28).
Functionality and Market Context
- The product is a solution for parenteral injection intended as a generic version of Fresenius Kabi's FDA-approved Levothyroxine Sodium injection (Compl. ¶28-29). The complaint alleges that Accord's product is "the same, or substantially the same" as Fresenius Kabi's commercial product and that Accord intends to manufacture, import, and sell it in the United States upon receiving FDA approval (Compl. ¶29-30).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint pleads infringement based on information Accord produced from its NDA under a confidentiality agreement, which allegedly confirms that the accused product meets all limitations of the asserted claims (Compl. ¶37, ¶50).
'669 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A liquid formulation comprising levothyroxine or a pharmaceutically acceptable salt thereof; | The complaint alleges Accord's NDA Product is a liquid formulation for parenteral injection containing the active ingredient levothyroxine sodium. | ¶28, ¶37 | col. 3:13-20 |
| a stabilizing agent comprising tromethamine; | The complaint alleges, based on confidential NDA data, that Accord's product contains the claimed stabilizing agent. | ¶37 | col. 4:7-13 |
| not more than 2% liothyronine (T3); and | The complaint alleges, based on confidential NDA data, that Accord's product meets this impurity limitation. | ¶37 | col. 6:50-52 |
| water; | The complaint alleges Accord's product is an injectable solution, which inherently contains water. | ¶28, ¶37 | col. 2:8-11 |
| wherein the formulation retains at least about 95% of the initial concentration...after storage for 12 months at 25±2° C... | The complaint alleges, based on confidential NDA data, that Accord's product meets this specific stability requirement. | ¶37 | col. 2:51-58 |
| and retains at least about 95% of the initial concentration...after storage for 2 months at 40±2° C. | The complaint alleges, based on confidential NDA data, that Accord's product meets this specific stability requirement under accelerated conditions. | ¶37 | col. 2:51-58 |
'190 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical product comprising a liquid formulation comprising levothyroxine or a pharmaceutically acceptable salt thereof, | The complaint alleges Accord's NDA Product is a liquid pharmaceutical product containing the active ingredient levothyroxine sodium. | ¶28, ¶50 | col. 26:14-21 |
| a stabilizing agent comprising an amine selected from one or more of tromethamine, bis(2-hydroxyethyl)-imino-tri(hydroxymethyl)methane, monoethanolamine, triethanolamine...and 2-amino-2-mythyl-1-propanol, | The complaint alleges, based on confidential NDA data, that Accord's product contains a stabilizing agent with an amine from this list. | ¶50 | col. 27:15-22 |
| and water, | The complaint alleges Accord's product is an injectable solution, which inherently contains water. | ¶28, ¶50 | col. 26:8-12 |
| wherein the formulation retains at least 95% of the initial concentration...after storage for two months at 40° C. | The complaint alleges, based on confidential NDA data, that Accord's product meets this specific stability requirement. | ¶50 | col. 26:56-62 |
| and retains at least 95% of the initial concentration...after storage for at least 12 months at room temperature. | The complaint alleges, based on confidential NDA data, that Accord's product meets this specific stability requirement. | ¶50 | col. 26:56-62 |
Identified Points of Contention:
- Factual Question: The central dispute will likely be factual: does the specific formulation detailed in Accord’s confidential NDA actually meet the quantitative stability requirements of the claims? The litigation will depend on the underlying stability data for Accord's product.
- Scope Question: For the '190 Patent, a question may arise as to whether the amine used in Accord’s product falls squarely within the claimed Markush group.
V. Key Claim Terms for Construction
For the ’669 Patent:
- The Term: "retains at least about 95% of the initial concentration"
- Context and Importance: This functional limitation defines the patentability of the formulation. The entire case may depend on whether Accord's product meets this specific, quantitative threshold for stability under the claimed conditions. Practitioners may focus on this term because proving infringement requires demonstrating that the accused product possesses this performance characteristic.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The use of "about" suggests the 95% figure is not a rigid, absolute boundary and may encompass values slightly below 95.0% (’669 Patent, col. 2:51-54). The specification discusses retaining "at least about 90%" in some embodiments, suggesting some flexibility around the claimed value (’669 Patent, col. 2:51-52).
- Evidence for a Narrower Interpretation: The claims explicitly recite "about 95%," a higher and more specific value than the "about 90%" discussed elsewhere in the specification. The examples in the patent provide specific data points that may be used to argue for a precise meaning centered on the 95% value (’669 Patent, Tables 1-4, col. 18-20).
For the ’190 Patent:
- The Term: "stabilizing agent"
- Context and Importance: The identity and function of the "stabilizing agent" are critical. The claim requires the agent to comprise a specific amine, and infringement turns on whether the corresponding component in Accord's product functions as a stabilizing agent in the context of the invention.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim uses "comprising," which is open-ended, suggesting the stabilizing agent could include the listed amine plus other components that contribute to stability (’190 Patent, col. 33:50). The specification describes the agent's role broadly as serving "to stabilize levothyroxine" (’190 Patent, col. 27:10-12).
- Evidence for a Narrower Interpretation: The patent teaches that the amine itself is the key stabilizing component, with a "stabilizing effect...unrelated to buffering" (’190 Patent, col. 28:46-50). An argument could be made that the "stabilizing agent" must be primarily the listed amine, and its function must be distinct from simple pH control.
VI. Other Allegations
- Willful Infringement: The complaint alleges that Accord had knowledge of the patents-in-suit before it submitted its NDA (Compl. ¶31, ¶40, ¶53). It further alleges that Accord has "no reasonable basis" for its Paragraph IV certification positions of non-infringement and invalidity (Compl. ¶41, ¶54). These allegations form the basis for a claim of willful infringement and a request for enhanced damages and attorneys' fees under 35 U.S.C. §§ 284 and 285.
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of evidentiary proof: Can Fresenius Kabi, using Accord's confidential NDA data, demonstrate that Accord's proposed generic product formulation will, in fact, meet the specific quantitative stability benchmarks recited in the asserted claims (e.g., retaining ≥95% potency after 12 months at room temperature)?
- A key question for the litigation, prompted by Accord's Paragraph IV certification, will be one of validity: Are the claimed stability profiles non-obvious in light of prior art attempts to create aqueous levothyroxine solutions? The case may turn on whether achieving the specific stability recited in the claims was an inventive step or merely the result of routine optimization of known stabilizing techniques.