DCT
1:23-cv-21684
Endo Par Innovation Co LLC v. Deva Holding As
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Endo Par Innovation Company, LLC (DE), Par Pharmaceutical, Inc. (NY), and Par Sterile Products, LLC (DE)
- Defendant: Deva Holding A.S. (Turkey)
- Plaintiff’s Counsel: The Law Office of JASON B. LATTIMORE, ESQ. LLC (with Axinn, Veltrop & Harkrider LLP as Of Counsel)
- Case Identification: 2:23-cv-21684, D.N.J., 10/31/2023
- Venue Allegations: Venue is alleged to be proper on the basis that the defendant is a foreign corporation organized under the laws of Turkey and may be sued in any judicial district.
- Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic epinephrine injection product constitutes an act of infringement of two patents covering stable epinephrine formulations and methods of their use.
- Technical Context: The technology concerns pharmaceutical formulations of injectable epinephrine engineered to minimize the formation of chemical degradants, thereby improving product stability, potency, and shelf-life for a critical emergency-use medication.
- Key Procedural History: Plaintiffs’ patents are listed in the FDA’s Orange Book in connection with their Adrenalin® brand epinephrine injection. The complaint states that Defendant submitted an ANDA seeking to market a generic version prior to patent expiry, including a Paragraph IV certification that the patents are invalid or not infringed, which forms the statutory basis for this lawsuit. Plaintiffs note they filed this action within the 45-day window following receipt of Defendant's notice letter. The complaint also certifies a pending action against a different defendant (BPI Labs, LLC) in the Middle District of Florida concerning the same patents but a different ANDA.
Case Timeline
| Date | Event |
|---|---|
| 2012-12-07 | Plaintiffs' 1 mL Adrenalin® Product NDA Approved |
| 2013-12-18 | Plaintiffs' 30 mL Adrenalin® Product NDA Approved |
| 2015-03-13 | Earliest Priority Date for ’876 and ’657 Patents |
| 2015-09-01 | ’876 Patent Issued |
| 2016-03-29 | ’657 Patent Issued |
| 2023-09-15 | Defendant sent Notice Letter regarding ANDA submission |
| 2023-10-31 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,119,876 - "Epinephrine Formulations"
Issued September 1, 2015
The Invention Explained
- Problem Addressed: The patent describes that prior epinephrine formulations have a limited shelf life due to chemical degradation of the active ingredient, L-epinephrine (Compl. ¶17). This degradation forms impurities, primarily epinephrine sulfonic acid (ESA) and D-epinephrine, a less therapeutically active version of the molecule, which reduces the product's potency and can be "pharmaceutically unacceptable" for emergency use (’876 Patent, col. 1:52-65; Compl. ¶18).
- The Patented Solution: The invention is a pharmaceutical composition that solves the stability problem by combining epinephrine with a specific suite of five additional types of agents—a tonicity regulating agent, a pH raising agent, an antioxidant, a pH lowering agent, and a transition metal complexing agent—each within specified concentration ranges (’876 Patent, Abstract). This precise combination is designed to control the chemical environment (e.g., pH, oxidation, metal catalysis) to minimize the formation of impurities, thereby maintaining potency and extending shelf life (’876 Patent, col. 2:18-28; Compl. ¶20).
- Technical Importance: Achieving a stable, long-shelf-life formulation for epinephrine is critical, as it is a first-line emergency treatment for life-threatening allergic reactions where reliable potency is paramount (Compl. ¶¶ 16, 18).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶32).
- Claim 1 recites the following essential elements:
- 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"
Issued March 29, 2016
The Invention Explained
- Problem Addressed: The patent, a continuation of the '876 patent application, addresses the same technical problem of epinephrine instability in pharmaceutical solutions (’657 Patent, col. 1:52-65).
- The Patented Solution: Rather than claiming the composition itself, this patent claims a method of treating various medical conditions by administering the specific stable formulation. The claim recites the same six-part composition as the ’876 Patent and links it to a method of use for a specified list of ailments, including anaphylaxis and bronchospasm (’657 Patent, Abstract; col. 2:48-51).
- Technical Importance: This patent extends protection from the formulation itself to its specific, intended medical uses, thereby protecting the market for using the improved composition to treat the conditions for which it was developed (Compl. ¶24).
Key Claims at a Glance
- The complaint asserts independent claim 1 (and dependent claim 20) (Compl. ¶¶ 46, 48).
- Claim 1 recites the following essential elements:
- A method of treating a condition comprising administering to a patient in need thereof a composition comprising:
- [The claim then recites the same six agent types and concentration ranges as Claim 1 of the ’876 Patent.]
- wherein the antioxidant comprises sodium bisulfite and/or sodium metabisulfite, and
- wherein the condition is selected from a group including anaphylaxis, bronchospasm, sensitivity reactions, and others.
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is "Defendant's Proposed Product," a generic Epinephrine Injection, USP, 1 mg/mL (30 mg/30 mL vial), for which Defendant Deva Holding A.S. has filed Abbreviated New Drug Application (ANDA) No. 217978 with the U.S. FDA (Compl. ¶26).
Functionality and Market Context
- The complaint alleges on information and belief that the Defendant's Proposed Product contains the same active ingredient in the same concentration as Plaintiffs' Adrenalin® product (Compl. ¶¶ 35, 54). It is intended as a generic substitute for Adrenalin®. The complaint further alleges that the proposed product label is "substantially identical" to the approved label for Adrenalin® and indicates the product for the "emergency treatment of allergic reactions (Type 1), including anaphylaxis" (Compl. ¶¶ 51-53).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
’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, | The complaint alleges on information and belief that the Defendant's Proposed Product comprises each of the claimed agents within the claimed concentration ranges. | ¶37 | col. 4:36-41 |
| in the range of about 6 to 8 mg/mL of a tonicity regulating agent, | The complaint alleges on information and belief that the Defendant's Proposed Product comprises each of the claimed agents within the claimed concentration ranges. | ¶37 | col. 8:60-63 |
| in the range of about 2.8 to 3.8 mg/mL of a pH raising agent, | The complaint alleges on information and belief that the Defendant's Proposed Product comprises each of the claimed agents within the claimed concentration ranges. | ¶37 | col. 4:29-33 |
| in the range of about 0.1 to 1.1 mg/mL of an antioxidant, | The complaint alleges on information and belief that the Defendant's Proposed Product comprises each of the claimed agents within the claimed concentration ranges. | ¶37 | col. 6:64-65 |
| in the range of about 0.001 to 0.010 mL/mL of a pH lowering agent, | The complaint alleges on information and belief that the Defendant's Proposed Product comprises each of the claimed agents within the claimed concentration ranges. | ¶37 | col. 7:32-37 |
| in the range of about 0.01 to 0.4 mg/mL of a transition metal complexing agent, | The complaint alleges on information and belief that the Defendant's Proposed Product comprises each of the claimed agents within the claimed concentration ranges. | ¶37 | col. 7:45-50 |
| wherein the antioxidant comprises sodium bisulfite and/or sodium metabisulfite. | The complaint alleges on information and belief that the Defendant's Proposed Product comprises an antioxidant that is sodium bisulfite and/or sodium metabisulfite. | ¶37 | col. 7:1-5 |
’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: | The complaint alleges Defendant will induce infringement by promoting, encouraging, and recommending that medical personnel perform the claimed method via the product's label. | ¶48, ¶53 | col. 2:48-51 |
| [the six-part composition, as recited above] | The complaint alleges the Defendant's Proposed Product is the claimed composition. | ¶56 | col. 27:35-48 |
| wherein the condition is selected from the group consisting of anaphylaxis, bronchospasm... | The complaint alleges the label for Defendant's Proposed Product states it is indicated for emergency treatment of allergic reactions, including anaphylaxis, thereby encouraging its use for the claimed condition. | ¶51, ¶53 | col. 28:44-50 |
Identified Points of Contention
- Technical Question: The complaint’s infringement allegations are based on "information and belief." A primary factual question for the court will be whether the specific formulation detailed in Defendant's confidential ANDA actually contains all six of the required agent types within the specific concentration ranges recited in the claims. The interpretation of the term "about" for each range may be critical.
- Scope Question: A potential point of dispute may arise over the definitions of the functional agent categories (e.g., "pH raising agent," "tonicity regulating agent"). The analysis may focus on whether Defendant's formulation contains six structurally distinct ingredients that each map to one of the claimed functions, or whether a single ingredient might be alleged to perform multiple claimed functions, which could raise questions about whether the claim limitations are separately met.
V. Key Claim Terms for Construction
The Term: "pH raising agent"
Context and Importance: The claims for both patents require a composition with six distinct functional agents. The definition of "pH raising agent" is critical because it must be present in addition to the other five agents. Practitioners may focus on this term because a defendant in an ANDA case might argue that one of its excipients, while not primarily added as a pH raising agent, has such an effect, or that it is not a "pH raising agent" in the manner contemplated by the patent.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification provides a list of potential pH raising agents that includes both acids/salts (lactate, tartarate) and strong bases (sodium hydroxide), suggesting the term is not limited to a single chemical class (’876 Patent, col. 5:4-11). This may support a functional definition, where any compound added that raises the pH to within a target range qualifies.
- Evidence for a Narrower Interpretation: The specification also describes the pH raising agent as part of a "buffer system" that provides "resistance to significant change in pH" and discusses pKa values (’876 Patent, col. 4:43-54, col. 4:3-10). This language could support a narrower construction requiring that the agent not only raise the pH but also have specific buffering characteristics.
The Term: "about"
Context and Importance: This term precedes every concentration range in the asserted independent claims. Its interpretation directly controls the literal scope of the claims. The infringement analysis will depend on whether the concentrations in Defendant's product, if not exactly matching the recited numbers, are nevertheless captured by the term "about."
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification frequently uses "about" when discussing preferred concentration ranges, suggesting the inventors did not intend for the claim ranges to be read as strict, absolute boundaries (e.g., ’876 Patent, col. 4:30-33). This may support an interpretation that includes normal manufacturing and measurement tolerances.
- Evidence for a Narrower Interpretation: The patents provide numerous formulation examples with precise concentrations that do not use the word "about" (’876 Patent, col. 25-28, Examples 5-18). A party could argue these examples inform the meaning of "about," limiting its scope to a very narrow range around the recited values.
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement of the ’657 patent by alleging that Defendant’s proposed product label will instruct and encourage medical personnel to administer the product to treat claimed conditions like anaphylaxis (Compl. ¶¶ 48, 53, 57). For the ’876 patent, the complaint includes standard allegations that Defendant will induce and contribute to infringement by selling the product with knowledge of the patent and its infringing use (Compl. ¶¶ 39-40).
- Willful Infringement: The complaint requests increased damages for "willful and deliberate infringement" in the prayer for relief (Compl. ¶¶ K, L). The factual basis for willfulness appears to be pre-suit knowledge of the patents, which the complaint alleges Defendant possessed at the time it submitted its Paragraph IV certification to the FDA, in part due to the patents' listing in the Orange Book (Compl. ¶28).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of compositional identity: does the defendant's formulation, as disclosed in its ANDA, literally contain all six classes of agents required by the asserted claims within the specified concentration ranges? The resolution of this question will depend on both the confidential ANDA data and the court's construction of the term "about."
- A key legal question will be one of induced infringement: for the ’657 method patent, does the defendant's proposed product label, by instructing the use of its generic product for treating anaphylaxis, demonstrate the specific intent required to encourage infringement of the patented method by healthcare providers?
- The case may also turn on a question of functional definition: will the court construe the claims to require six structurally distinct ingredients, each performing a single claimed function, or can a single compound in the accused formulation satisfy more than one functional limitation (e.g., acting as both a "tonicity regulating agent" and a "pH raising agent")?