DCT
1:25-cv-02365
Endo USA Inc v. Baxter Healthcare Corp
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Endo USA, Inc. (Delaware) and Endo Operations Limited (Ireland)
- Defendant: Baxter Healthcare Corporation (Delaware)
- Plaintiff’s Counsel: O'Melveny & Myers LLP; McDonnell Boehnen Hulbert & Berghoff LLP
- Case Identification: 1:25-cv-02365, N.D. Ill., 03/05/2025
- Venue Allegations: Venue is alleged to be proper as Defendant maintains a regular and established place of business within the judicial district.
- Core Dispute: Plaintiff seeks a declaratory judgment that Defendant’s ready-to-use epinephrine injection product, which is preparing for a U.S. launch, will infringe three patents related to stable, low-concentration epinephrine formulations.
- Technical Context: The technology concerns ready-to-use injectable epinephrine solutions formulated to be stable without refrigeration, addressing the risks of dilution errors, microbial contamination, and chemical degradation associated with prior concentrated forms.
- Key Procedural History: Plaintiff Endo listed U.S. Patent Nos. 11,207,280 and 12,133,837 in the FDA’s Orange Book for its own Adrenalin® bags product. The complaint alleges that Defendant Baxter had knowledge of the '280 patent no later than its Orange Book listing date and of both the '280 and '837 patents via a notice letter from Plaintiff's counsel. Defendant Baxter’s accused product received FDA approval via a 505(b)(2) New Drug Application (NDA) shortly before the complaint was filed.
Case Timeline
| Date | Event |
|---|---|
| 2012-12-07 | FDA approves Plaintiff's Adrenalin® single-dose vials (NDA 204200) |
| 2012-12-18 | FDA approves Plaintiff's Adrenalin® multi-dose vials (NDA 204640) |
| 2018-03-23 | Earliest Priority Date for '719, '280, and '837 Patents |
| 2021-07-27 | U.S. Patent No. 11,071,719 issues |
| 2021-12-28 | U.S. Patent No. 11,207,280 issues |
| 2023-05-10 | Plaintiff lists '280 Patent in the FDA Orange Book |
| 2023-09-29 | Defendant files NDA for its Epinephrine Bags |
| 2024-11-05 | U.S. Patent No. 12,133,837 issues |
| 2024-11-06 | Plaintiff lists '837 Patent in the FDA Orange Book |
| 2025-02-28 | FDA approves Defendant's Epinephrine Bags (NDA 218475) |
| 2025-03-05 | Complaint for Declaratory Judgment filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,071,719, "Epinephrine Compositions and Containers", issued July 27, 2021
The Invention Explained
- Problem Addressed: The patent’s background describes the challenges with conventional epinephrine formulations, which are supplied in concentrated form and must be diluted before use. This process creates risks of dilution errors, microbial contamination, and limited shelf-life due to the chemical instability of diluted epinephrine, which degrades rapidly via oxidation and racemization when exposed to air or light (Compl. ¶¶ 23-24; ’719 Patent, col. 2:4-15, col. 2:46-62).
- The Patented Solution: The invention is a method for producing a storage-stable, low-concentration, ready-to-inject epinephrine composition that is "substantially antioxidant-free." The solution achieves stability by controlling several parameters simultaneously: maintaining a low dissolved oxygen level, adjusting the pH to a specific acidic range (3.0-4.7), and including a metal ion chelator to prevent metal-ion-stimulated autoxidation ('719 Patent, Abstract; col. 5:40-54).
- Technical Importance: This approach creates the first FDA-approved, manufacturer-prepared, premixed intravenous (IV) bag of epinephrine, removing the need for clinicians to perform risky and time-consuming bedside dilutions (Compl. ¶27; ’719 Patent, col. 2:56-62).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶34).
- Claim 1 is a method claim with the following essential elements:
- Combining an aqueous carrier with epinephrine to a concentration of ≤ 0.07 mg/mL.
- Wherein substantially all epinephrine is the R-isomer.
- Wherein the carrier has dissolved oxygen of ≤ 2 ppm.
- Adjusting the pH to between 3.0-4.7.
- Including a metal ion chelator (EDTA, EGTA, or DPTA) at 1-50 mcg/mL.
- Packaging the composition into a container under an inert gas.
- Sterilizing the composition.
- Wherein the final composition is substantially antioxidant-free and meets specific impurity and S-isomer limits after one month of storage.
- The complaint reserves the right to assert other claims (Compl. ¶22).
U.S. Patent No. 11,207,280, "Epinephrine Compositions and Containers", issued December 28, 2021
The Invention Explained
- Problem Addressed: As with its related patent, the '280 Patent addresses the instability of ready-to-use epinephrine solutions, which are susceptible to degradation from oxidation and racemization, particularly when diluted for clinical use (’280 Patent, col. 2:4-15, col. 2:46-62).
- The Patented Solution: The patent claims both a method and a composition for a sterile, storage-stable, ready-to-inject epinephrine solution. The invention combines an aqueous carrier, epinephrine, and a metal ion chelator at specific concentrations, adjusts the pH to a narrow range (3.5-4.7), and uses a terminal sterilization process (autoclaving) that limits the increase of the inactive S-isomer to no more than 4% (’280 Patent, Abstract; col. 5:40-54).
- Technical Importance: The invention enables the production of a terminally sterilized, ready-to-use epinephrine IV product that remains stable over its shelf life, improving patient safety and clinical convenience (Compl. ¶27; ’280 Patent, col. 2:56-62).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (method) and independent claim 10 (composition) (Compl. ¶¶ 53, 62).
- Claim 1 is a method claim with the following essential elements:
- Combining an aqueous carrier, epinephrine (≤ 0.07 mg/ml), and a metal ion chelator (1-50 ug/ml), wherein substantially all epinephrine is the R-isomer.
- Adjusting the pH to between 3.5-4.7.
- Packaging the composition into a container under an inert gas.
- Autoclaving the composition to sterility, wherein sterilization increases S-isomer content to no more than 4%.
- Claim 10 is a composition claim with the following essential elements:
- A sterile, storage-stable, ready-to-inject epinephrine composition comprising an aqueous carrier, epinephrine, and a metal ion chelator.
- Wherein epinephrine is ≤ 0.07 mg/ml, substantially all is the R-isomer, and pH is 3.5-4.7.
- Wherein the composition is substantially antioxidant-free.
- Wherein the composition has specific total impurity and S-isomer limits after one month of storage at 25° C.
- The complaint reserves the right to assert other claims (Compl. ¶22).
U.S. Patent No. 12,133,837, "Epinephrine Compositions and Containers", issued November 5, 2024
Technology Synopsis
This patent, part of the same family, addresses the degradation of diluted epinephrine by claiming a sterile, storage-stable, ready-to-inject composition. The invention achieves stability by combining an aqueous carrier, epinephrine, a tonicity agent, and a metal ion chelator from a specific chemical class (bicarboxylic, tricarboxylic, or aminopolycarboxylic acid), while controlling for pH, R-isomer percentage, and total impurities after storage (Compl. ¶¶ 23-24, 79).
Asserted Claims
Independent claim 1 (composition) and independent claim 10 (method) are asserted (Compl. ¶¶ 78, 88).
Accused Features
The complaint alleges that Baxter's Epinephrine Bags, as a composition and a product of a method, meet the claimed limitations. It specifically alleges the product is sterile and storage-stable, contains an aqueous carrier, epinephrine, a tonicity agent (sodium chloride), and an aminopolycarboxylic acid chelator (EDTA), all within the claimed concentration and pH ranges, and meets the required R-isomer and impurity profiles (Compl. ¶¶ 80-87).
III. The Accused Instrumentality
Product Identification
Baxter's Epinephrine in 0.9% Sodium Chloride Injection product, referred to as "Baxter's Epinephrine Bags" (Compl. ¶1).
Functionality and Market Context
- The accused product is a ready-to-use, sterile, premixed solution for intravenous administration, intended to increase mean arterial blood pressure in adults with hypotension associated with septic shock (Compl. ¶1). The product label allegedly discloses a formulation containing 64 µg/mL of epinephrine, 9.0 mg/mL of sodium chloride, 0.05 mg/mL of sodium metabisulfite (an antioxidant), and 0.032 mg/mL of edetate disodium (EDTA), with a pH adjusted to between 3.4 and 4.5 (Compl. ¶¶ 29-30). The complaint alleges the product is shelf-stable for 12 months (Compl. ¶45).
- The complaint alleges that Baxter is preparing to launch this product in the United States following recent FDA approval, positioning it to compete directly with Plaintiff's own Adrenalin® bags (Compl. ¶¶ 1, 28).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
11,071,719 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of producing a storage stable ready-to-inject epinephrine composition, comprising: combining an aqueous pharmaceutically acceptable carrier with epinephrine in an amount such that the epinephrine is present in the ready-to-inject epinephrine composition at a concentration of equal or less than 0.07 mg/mL; | Defendant's method produces Baxter's Epinephrine Bags, which are storage stable and contain 64 µg/mL (0.064 mg/mL) of epinephrine in an aqueous carrier. | ¶36, ¶37 | col. 6:7-13 |
| wherein substantially all of the epinephrine is an R-isomer; | On information and belief, the accused product contains substantially all R-isomer epinephrine to comply with USP standards and to achieve the required biological activity, as the S-isomer is inactive. | ¶38 | col. 5:32-36 |
| wherein the aqueous pharmaceutically acceptable carrier has dissolved oxygen in an amount of equal or less than 2 ppm; | On information and belief, Defendant's process limits dissolved oxygen to ≤ 2 ppm to prevent rapid destruction of the R-isomer epinephrine. | ¶39 | col. 5:45-50 |
| adjusting the pH of the ready-to-inject epinephrine composition to a pH of between 3.0-4.7; | The accused product's label states the pH is between 3.4 and 4.5. | ¶40 | col. 5:42-44 |
| including into the ready-to-inject epinephrine composition a metal ion chelator selected from the group consisting of EDTA... at a concentration of between about 1 and 50 mcg/mL; | The accused product contains 0.032 mg/mL (32 µg/mL) of EDTA. | ¶41 | col. 7:34-54 |
| packaging the ready-to-inject epinephrine composition into a container under an inert gas; | On information and belief, the accused product is packaged under an inert gas to achieve sterility and stability. | ¶42 | col. 5:51-54 |
| sterilizing the ready-to-inject epinephrine composition; | The accused product is sold as sterile. | ¶43 | col. 5:50-51 |
| wherein the ready-to-inject epinephrine composition is substantially antioxidant-free and has, after storage of at least one month, total impurities of equal or less than 0.7% and equal or less than 4% S-isomer content. | The accused product allegedly meets the patent’s definition of "substantially antioxidant-free" and, on information and belief, meets the impurity and S-isomer limits after storage to ensure its 12-month shelf life. | ¶44, ¶45 | col. 8:7-27 |
- Identified Points of Contention:
- Scope Questions: A primary dispute may arise over the term "substantially antioxidant-free." The complaint acknowledges the accused product contains sodium metabisulfite, an antioxidant (Compl. ¶44). The infringement allegation hinges on the argument that the amount present (0.05 mg/mL) is "equal or less than 0.01 wt%," which the patent specification explicitly defines as meeting the "substantially antioxidant-free" limitation ('719 Patent, col. 8:7-15). This raises the question of whether the specification's definition or a plain meaning of "free" will control the claim's scope.
- Technical Questions: The complaint alleges on "information and belief" that the manufacturing process limits dissolved oxygen to ≤ 2 ppm to prevent degradation (Compl. ¶39). What evidence supports this specific quantitative limit, as opposed to a general goal of minimizing oxygen, will be a question for discovery.
11,207,280 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of producing a sterile and storage stable ready-to-inject epinephrine composition, comprising: combining an aqueous pharmaceutically acceptable carrier with epinephrine and a metal ion chelator such that the epinephrine has a concentration of equal or less than 0.07 mg/ml, wherein the metal ion chelator is present...at a concentration of between about 1 and 50 ug/ml, and wherein substantially all of the epinephrine is an R-isomer; | Defendant's method produces Baxter's Epinephrine Bags, which are sterile and stable. The bags allegedly contain epinephrine (0.064 mg/mL), a chelator (EDTA at 32 µg/mL), and substantially all R-isomer epinephrine. | ¶55, ¶56, ¶57, ¶58 | col. 11:54-61 |
| adjusting the pH of the ready-to-inject epinephrine composition to a pH of between 3.5-4.7; | The accused product's label states the pH is between 3.4 and 4.5, which overlaps with the claimed range. | ¶59 | col. 11:62-64 |
| packaging the ready-to-inject epinephrine composition into a container under an inert gas; | On information and belief, the accused product is packaged under an inert gas to achieve sterility. | ¶60 | col. 11:65-66 |
| autoclaving the ready-to-inject epinephrine composition to sterility, wherein sterilization increases S-isomer content to no more than 4%. | On information and belief, the accused product is autoclaved to achieve sterility and USP compliance, and this process results in S-isomer content of no more than 4% to maintain efficacy. | ¶61 | col. 12:1-4 |
| Claim Element (from Independent Claim 10) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A sterile storage stable ready-to-inject epinephrine composition, comprising: an aqueous pharmaceutically acceptable carrier containing epinephrine and a metal ion chelator; | Baxter's Epinephrine Bags are a sterile, stable composition containing an aqueous carrier, epinephrine, and EDTA as a metal ion chelator. | ¶64, ¶65, ¶66 | col. 12:28-32 |
| wherein the epinephrine is present at a concentration of equal or less than 0.07 mg/ml, wherein substantially all of the epinephrine is an R-isomer, and wherein the composition has a pH of between 3.5-4.7; | The accused product contains 64 µg/mL of epinephrine, is alleged to contain substantially all R-isomer epinephrine, and has a pH of 3.4-4.5, which overlaps with the claimed range. | ¶66, ¶67, ¶68 | col. 12:33-37 |
| wherein the ready-to-inject epinephrine composition is substantially antioxidant-free; | The accused product contains an antioxidant but allegedly meets the patent's specific definition of "substantially antioxidant-free" as containing ≤ 0.01 wt% of antioxidant. | ¶69 | col. 8:11-19 |
| wherein the...composition has, after storage of at least one month at 25° C., total impurities of equal or less than 0.7% and equal or less than 4% S-isomer content. | On information and belief, the accused product meets these impurity and S-isomer limits to achieve its 12-month shelf life and efficacy. | ¶70 | col. 12:41-45 |
- Identified Points of Contention:
- Scope Questions: As with the ’719 Patent, the interpretation of "substantially antioxidant-free" in claim 10 will be a central dispute, given the presence of sodium metabisulfite in the accused product (Compl. ¶69).
- Technical Questions: For method claim 1, the allegation that the product is "autoclaved" is made on information and belief, inferred from the product being sterile and the patent identifying autoclaving as a sterilization method (’280 Patent, col. 2:65-66; Compl. ¶61). Whether other sterilization methods are used and whether they meet the claim limitation will be an evidentiary question.
V. Key Claim Terms for Construction
The Term: "substantially antioxidant-free" (asserted in '719 Claim 1, '280 Claim 10)
- Context and Importance: This term is critical because the accused product contains a disclosed antioxidant (sodium metabisulfite). Infringement depends on this term being construed to permit the presence of a small, specific amount of an antioxidant, rather than requiring its complete absence. Practitioners may focus on this term because it appears to be the most direct point of non-infringement that the Plaintiff has proactively addressed with a specific construction theory in the complaint (Compl. ¶¶ 44, 69).
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation (Plaintiff's likely view): The specifications of the patents-in-suit provide an explicit definition, stating that "antioxidant-free and storage stable ready-to-administer epinephrine composition will include antioxidants in an amount of equal or less than about 0.01 wt%" (’719 Patent, col. 8:13-15; ’280 Patent, col. 8:11-19). This language suggests the inventors defined the term to include such de minimis quantities.
- Evidence for a Narrower Interpretation (Defendant's likely view): A party could argue that the plain and ordinary meaning of "free" implies a complete absence. The patent Abstract also describes the invention as "preferably anti-oxidant free," which could be used to argue that the inclusion of any antioxidant is a deviation from the core invention, and the specification's definition is merely one possible, non-limiting embodiment (’719 Patent, Abstract; ’280 Patent, Abstract).
The Term: "substantially all of the epinephrine is an R-isomer" (asserted in '719 Claim 1, '280 Claim 1)
- Context and Importance: This term defines the required purity of the active pharmaceutical ingredient. Its construction is important because infringement is alleged on "information and belief" based on the product's need to be effective and USP compliant, rather than on direct measurement (Compl. ¶¶ 38, 58). The parties may dispute what numerical percentage satisfies the "substantially all" requirement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a potential quantitative benchmark, stating that "substantially all (i.e., at least about 98 mol %) of the epinephrine is an R-isomer" (’719 Patent, col. 3:13-14; ’280 Patent, col. 3:13-14). This could support a reading that any amount at or above this threshold meets the limitation.
- Evidence for a Narrower Interpretation: A party could argue that "substantially all" requires a level of purity higher than 98%, especially given the patent's goal of minimizing the "biologically inactive S-isomer" (’719 Patent, col. 2:1-2). They may argue the 98% value is an example, not a floor, and that the term's meaning should be closer to complete purity.
VI. Other Allegations
Indirect Infringement
The complaint alleges inducement of infringement for the asserted method claims. The basis for this allegation is that Defendant's product, through its label and instructions, will cause and encourage healthcare professionals to administer the product, thereby performing the infringing methods (Compl. ¶¶ 46, 62, 88). Contributory infringement is also alleged.
Willful Infringement
Willfulness is alleged for all three patents. For the '719 patent, the complaint alleges knowledge since its issue date on July 27, 2021 (Compl. ¶48). For the '280 and '837 patents, willfulness is based on pre-suit knowledge from their respective listings in the FDA's Orange Book (May 10, 2023, and Nov. 6, 2024) and, for both, a direct notice letter sent from Plaintiff's counsel to Defendant on March 4, 2025, one day before the suit was filed (Compl. ¶¶ 73, 101).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of definitional scope: can the term "substantially antioxidant-free" be construed to read on a product containing a measurable quantity of a known antioxidant (sodium metabisulfite), based on a specific quantitative definition provided in the patent's specification, or will a plain meaning of "free" prevail?
- A key evidentiary question will concern the proof of process: for the asserted method claims, what discovery evidence will support the "information and belief" allegations that Defendant's manufacturing process necessarily uses specific steps like "autoclaving" and achieves specific quantitative outcomes like dissolved oxygen levels of "equal or less than 2 ppm"?
- The case may also turn on a question of commercial timing and intent: given that the complaint was filed for declaratory judgment immediately following the FDA approval of Defendant's product and just one day after a notice letter was sent, the development of facts around pre-suit knowledge and willfulness will be a significant focus.