DCT
1:24-cv-01065
Endo Operations Ltd v. FK Fresenius Kabi USA LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Endo Operations, Ltd. (Ireland)
- Defendant: Fresenius Kabi USA, LLC (Delaware)
- Plaintiff’s Counsel: Axinn, Veltrop & Harkrider LLP
- Case Identification: 1:24-cv-01065, D. Del., 09/24/2024
- Venue Allegations: Venue is asserted on the grounds that Defendant is a limited liability company organized under the laws of Delaware and has allegedly committed acts of infringement in the district, including offering to sell and selling products.
- Core Dispute: Plaintiff alleges that Defendant's proposed generic epinephrine injection, submitted to the FDA for approval, will infringe three patents covering stable epinephrine formulations and their methods of use.
- Technical Context: The technology relates to pharmaceutical formulations of injectable epinephrine that are stabilized to minimize the formation of impurities, thereby increasing product potency and shelf life for use in emergency treatments like anaphylaxis.
- Key Procedural History: This lawsuit was initiated under the Hatch-Waxman Act following Defendant's submission of a supplement to its New Drug Application (NDA) seeking approval to market a generic epinephrine product. Plaintiff alleges this filing included a Paragraph IV certification stating that the patents-in-suit are invalid, unenforceable, or will not be infringed. The patents-in-suit are listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (“Orange Book”) for Plaintiff’s Adrenalin® brand epinephrine injection. The action was filed within the 45-day statutory window after Plaintiff received Defendant's notice letter.
Case Timeline
| Date | Event |
|---|---|
| 2012-03-XX | Endo's predecessor (JHP) seeks FDA approval for original Adrenalin® formulation |
| 2012-12-07 | Endo's NDA No. 204200 (1 mL Adrenalin® Product) approved by FDA |
| 2013-12-18 | Endo's NDA No. 204640 (30 mL Adrenalin® Product) approved by FDA |
| 2015-03-13 | Earliest Priority Date for '876, '657, and '592 Patents |
| 2015-03-XX | Par Sterile submits supplemental NDA for reformulated 30 mL Adrenalin® Product |
| 2015-09-01 | U.S. Patent No. 9,119,876 issues |
| 2016-01-XX | Par Sterile submits supplemental NDA for reformulated 1 mL Adrenalin® Product |
| 2016-01-XX | FDA approves supplemental NDA for reformulated 30 mL Adrenalin® Product |
| 2016-03-29 | U.S. Patent No. 9,295,657 issues |
| 2016-09-XX | FDA approves supplemental NDA for reformulated 1 mL Adrenalin® Product |
| 2018-11-20 | U.S. Patent No. 10,130,592 issues |
| 2024-08-30 | Defendant sends Notice Letter regarding its NDA supplement |
| 2024-09-03 | Plaintiff receives Notice Letter |
| 2024-09-24 | Complaint for Patent Infringement filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,119,876 - “Epinephrine Formulations”
- Patent Identification: U.S. Patent No. 9,119,876, titled “Epinephrine Formulations,” issued on September 1, 2015. (Compl. ¶10).
The Invention Explained
- Problem Addressed: The patent’s background section describes how existing epinephrine solutions were prone to degradation, forming impurities such as epinephrine sulfonic acid (ESA) and D-epinephrine, which reduce the product's potency and limit its shelf life. (Compl. ¶¶18-19; ’876 Patent, col. 2:51-61).
- The Patented Solution: The invention is a stable pharmaceutical composition comprising epinephrine and a specific combination of excipients—a tonicity regulating agent, a pH raising agent, an antioxidant, a pH lowering agent, and a transition metal complexing agent—each within defined concentration ranges. (Compl. ¶21; ’876 Patent, Abstract). This specific balance of components is designed to minimize the formation of degradants and maintain the racemic balance of the active ingredient. (’876 Patent, col. 2:19-24; Compl. ¶21).
- Technical Importance: This formulation technology allowed for the development of an epinephrine product that met stricter FDA purity requirements, resulting in improved stability and a longer shelf life. (Compl. ¶¶19-21).
Key Claims at a Glance
- The complaint asserts independent claim 1. (Compl. ¶38).
- The essential elements of independent claim 1 are:
- A composition comprising:
- in the range of about 0.5 to 1.5 mg/mL of epinephrine and/or salts thereof,
- in the range of about 6 to 8 mg/mL of a tonicity regulating agent,
- in the range of about 2.8 to 3.8 mg/mL of a pH raising agent,
- in the range of about 0.1 to 1.1 mg/mL of an antioxidant,
- in the range of about 0.001 to 0.010 mL/mL of a pH lowering agent, and
- in the range of about 0.01 to 0.4 mg/mL of a transition metal complexing agent,
- wherein the antioxidant comprises sodium bisulfite and/or sodium metabisulfite.
U.S. Patent No. 9,295,657 - “Epinephrine Formulations”
- Patent Identification: U.S. Patent No. 9,295,657, titled “Epinephrine Formulations,” issued on March 29, 2016. (Compl. ¶11).
The Invention Explained
- Problem Addressed: The patent addresses the need for effective treatment of conditions such as anaphylaxis using a stable and potent epinephrine product, implicitly referencing the degradation problems outlined in its parent applications. (’657 Patent, col. 2:6-9).
- The Patented Solution: This patent claims methods of using the stable epinephrine formulations, such as the one claimed in the ’876 patent, to treat a specified group of medical conditions. (Compl. ¶25; ’657 Patent, Abstract). The core of the invention is the administration of the specific formulation to a patient for therapeutic purposes. (’657 Patent, col. 2:50-52).
- Technical Importance: The invention extends patent protection from the composition itself to the specific, commercially important methods of its clinical use. (Compl. ¶25).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claim 20. (Compl. ¶¶52-53).
- The essential elements of independent claim 1 are:
- A method of treating a condition comprising administering to a patient in need thereof a composition comprising:
- [The six-part composition as recited in claim 1 of the ’876 patent].
- wherein the antioxidant comprises sodium bisulfite and/or sodium metabisulfite, and
- wherein the condition is selected from a specified group that includes anaphylaxis.
U.S. Patent No. 10,130,592 - “Epinephrine Formulations”
- Patent Identification: U.S. Patent No. 10,130,592, titled “Epinephrine Formulations,” issued on November 20, 2018. (Compl. ¶12).
Technology Synopsis
- This patent, part of the same family, also addresses the problem of epinephrine degradation. It discloses a composition that uses a specific buffer system comprising tartaric acid to provide resistance to pH change. The claims require that the formulation maintains a specific pH and comprises 3% or less of the D-Epinephrine impurity after 18 months of storage under defined conditions, ensuring long-term stability. (Compl. ¶¶26, 72; ’592 Patent, col. 2:6-11, Claim 1).
Asserted Claims
- The complaint asserts independent claim 1. (Compl. ¶72).
Accused Features
- The complaint alleges on information and belief that Defendant's proposed product is a composition comprising epinephrine, a tonicity agent, a buffer system with tartaric acid, an antioxidant, a preservative, and a transition metal complexing agent, all within the claimed parameters. (Compl. ¶76).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is Defendant’s “FK Proposed Product,” identified as an “epinephrine injection, 30 mg/30 mL, Multi-Dose Vial” for which Defendant seeks FDA approval under NDA No. 215425. (Compl. ¶¶28-29).
Functionality and Market Context
- The FK Proposed Product is an injectable formulation containing the active ingredient epinephrine. (Compl. ¶¶40, 59, 74). The complaint alleges that the product is a proposed generic equivalent to Plaintiff's Adrenalin® product and that its label will indicate it for the emergency treatment of Type 1 allergic reactions, including anaphylaxis. (Compl. ¶¶57-58). To gain approval, Defendant must allegedly show that its proposed labeling is the same as that of Adrenalin®, except for information identifying the manufacturer. (Compl. ¶55).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
'876 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A composition comprising: in the range of about 0.5 to 1.5 mg/mL of epinephrine and/or salts thereof, | Based on information and belief, the FK Proposed Product is a composition that contains epinephrine within the claimed concentration range. | ¶42 | col. 3:32-34 |
| in the range of about 6 to 8 mg/mL of a tonicity regulating agent, | Based on information and belief, the FK Proposed Product contains a tonicity regulating agent within the claimed concentration range. | ¶42 | col. 3:55-58 |
| in the range of about 2.8 to 3.8 mg/mL of a pH raising agent, | Based on information and belief, the FK Proposed Product contains a pH raising agent within the claimed concentration range. | ¶42 | col. 3:45-47 |
| in the range of about 0.1 to 1.1 mg/mL of an antioxidant, | Based on information and belief, the FK Proposed Product contains an antioxidant within the claimed concentration range. | ¶42 | col. 5:2-4 |
| in the range of about 0.001 to 0.010 mL/mL of a pH lowering agent, and | Based on information and belief, the FK Proposed Product contains a pH lowering agent within the claimed concentration range. | ¶42 | col. 7:42-44 |
| in the range of about 0.01 to 0.4 mg/mL of a transition metal complexing agent, | Based on information and belief, the FK Proposed Product contains a transition metal complexing agent within the claimed concentration range. | ¶42 | col. 6:23-25 |
| wherein the antioxidant comprises sodium bisulfite and/or sodium metabisulfite. | Based on information and belief, the antioxidant in the FK Proposed Product is sodium bisulfite and/or sodium metabisulfite. | ¶42 | col. 7:17-20 |
'657 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating a condition comprising administering to a patient in need thereof a composition comprising: | Defendant is alleged to induce medical personnel to perform this step by providing the FK Proposed Product with a label that instructs its use for treating allergic reactions. | ¶¶53, 58, 62 | col. 2:50-52 |
| [the six-part composition claimed in the ’876 patent] | The complaint alleges that the FK Proposed Product is the composition with all the claimed components in the claimed concentration ranges. | ¶61 | col. 3:39-7:27 |
| wherein the antioxidant comprises sodium bisulfite and/or sodium metabisulfite, | The complaint alleges the FK Proposed Product's antioxidant is sodium bisulfite and/or sodium metabisulfite. | ¶61 | col. 7:24-27 |
| and wherein the condition is selected from the group consisting of anaphylaxis, bronchospasm... | The label for the FK Proposed Product allegedly states it is indicated for emergency treatment of allergic reactions, including anaphylaxis, thereby encouraging its administration for a claimed condition. | ¶58 | col. 2:5-12 |
- Identified Points of Contention:
- Scope Questions: All asserted independent claims rely on concentration ranges qualified by the term "about." A primary point of contention may be the proper construction of "about," which will determine whether the precise concentrations in Defendant's product fall within the literal scope of the claims.
- Technical Questions: The complaint is based on "information and belief" and does not contain the specific formulation details from Defendant's NDA. The central technical question is whether discovery will confirm that the FK Proposed Product actually contains every claimed ingredient within the claimed concentration ranges. Any deviation could form the basis of a non-infringement defense.
V. Key Claim Terms for Construction
The Term: "about"
Context and Importance: This term modifies every numerical concentration range in the asserted independent claims of the '876 and '657 patents. Its interpretation is dispositive for literal infringement; a broader reading increases the likelihood of capturing Defendant's formulation, while a narrower reading may provide a path to non-infringement. Practitioners may focus on this term because infringement of these composition-based claims depends entirely on a quantitative comparison.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The repeated and consistent use of "about" for every range suggests the patentee deliberately intended flexibility and did not wish to be bound by the exact numerical endpoints. The specification does not provide an explicit definition, potentially leaving its meaning open to a broader, context-dependent interpretation by one of ordinary skill in the art.
- Evidence for a Narrower Interpretation: The patents provide numerous examples with specific concentrations (e.g., ’876 Patent, col. 25-28, Examples 1-18). A party could argue that the scope of "about" should be informed by the level of precision and variation demonstrated in these embodiments or by the number of significant digits recited in the claims.
The Term: "pH raising agent"
Context and Importance: Required by claim 1 of both the '876 and '657 patents, this term's definition is critical. The '876 patent specification states this agent "comprises a buffer system" ('876 Patent, col. 3:47-48), raising the question of whether the term requires a compound with buffering capacity or if any substance that raises pH suffices. This is significant because the related '592 patent explicitly claims a "buffer system," suggesting the patentee knew how to distinguish the terms.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification lists a variety of potential pH raising agents, including strong bases like sodium hydroxide alongside compounds that can form buffer systems. ('876 Patent, col. 4:17-24). This may support a construction that does not strictly require buffering functionality.
- Evidence for a Narrower Interpretation: The specification repeatedly links the "pH raising agent" to providing "resistance to significant pH change," a key function of a buffer. ('876 Patent, col. 3:47-54). A party may argue that this functional language limits the claim scope to agents that actually perform a buffering role, not just any base.
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement and contributory infringement for all three patents. (Compl. ¶¶44-45, 62-65, 78-79). For the method claims of the '657 patent, the primary theory is inducement, alleging Defendant's product label will encourage and instruct medical personnel to administer the product to treat claimed conditions like anaphylaxis. (Compl. ¶¶53, 58, 62). For the composition claims of the '876 and '592 patents, the complaint alleges the FK Proposed Product is a material part of the claimed invention and is not suitable for substantial non-infringing uses. (Compl. ¶¶45, 79).
- Willful Infringement: The complaint alleges that Defendant was aware of the Patents-in-Suit when it submitted its NDA supplement, asserting pre-suit knowledge as a basis for willfulness. (Compl. ¶33). Plaintiff seeks enhanced damages for willful and deliberate infringement of all three patents. (Compl., Prayer for Relief ¶¶Q-S).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of factual correspondence: Does the precise formulation of the FK Proposed Product, as will be detailed in its confidential NDA, contain every element recited in the asserted claims at a concentration that falls within the claimed numerical ranges? The outcome for the composition patents ('876 and '592) will depend almost entirely on this evidentiary question.
- A key legal battle will be over definitional scope: How broadly will the court construe the term "about"? This claim construction dispute is critical, as a narrow interpretation could excuse minor deviations in concentration, while a broad one could capture formulations that are not mathematically identical to the claim language.
- For the method patent ('657), a key question will be one of induced intent: Can Plaintiff demonstrate that Defendant’s product label not only describes a use that overlaps with the claimed method but does so in a manner that reflects a specific intent to encourage medical professionals to perform all steps of the patented method?