DCT
8:23-cv-01953
Endo Par Innovation Co LLC v. BPI Labs LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Endo Par Innovation Company, LLC; Par Pharmaceutical, Inc.; and Par Sterile Products, LLC (Delaware/New York)
- Defendant: BPI Labs, LLC and Belcher Pharmaceuticals, LLC (Florida)
- Plaintiff’s Counsel: Bedell, Dittmar, Devault, Pillans & Coxe, P.A.; Axinn, Veltrop & Harkrider LLP
- Case Identification: 8:23-cv-01953, M.D. Fla., 08/29/2023
- Venue Allegations: Venue is alleged to be proper based on Defendants having a regular and established place of business within the district, and on Defendants having consented to venue in pre-suit correspondence.
- Core Dispute: Plaintiffs allege that Defendants' submission of a supplemental New Drug Application (sNDA) for a generic epinephrine injection constitutes an act of infringement of two patents covering the formulation and method of use of Plaintiffs' Adrenalin® product.
- Technical Context: The technology concerns stable, injectable pharmaceutical formulations of epinephrine, a critical drug for treating life-threatening allergic reactions, which are designed to minimize the formation of impurities and thereby improve potency and shelf life.
- Key Procedural History: This action was filed under the Hatch-Waxman Act following Plaintiffs' receipt of a Paragraph IV notice letter from Defendants concerning a proposed generic version of Adrenalin®. The complaint was filed within the 45-day statutory window, which may trigger a 30-month stay on the FDA's approval of the Defendants' product. The patents-in-suit are listed in the FDA's Orange Book.
Case Timeline
| Date | Event |
|---|---|
| 2012-12-07 | Plaintiff's 1 mL Adrenalin® Product NDA approved |
| 2013-12-18 | Plaintiff's 30 mL Adrenalin® Product NDA approved |
| 2014-07-29 | Defendant BPI Labs' original NDA No. 205029 approved |
| 2015-03-13 | Earliest Priority Date for ’876 and ’657 Patents |
| 2015-09-01 | ’876 Patent Issued |
| 2016-03-29 | ’657 Patent Issued |
| 2023-07-17 | Defendants send "First Notice Letter" to Plaintiffs |
| 2023-08-09 | Defendants send "Second Notice Letter" to Plaintiffs |
| 2023-08-29 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,119,876 - “Epinephrine Formulations” (Issued Sep. 1, 2015)
The Invention Explained
- Problem Addressed: The patent's background section describes how prior epinephrine formulations have a limited shelf life due to chemical degradation, particularly the formation of impurities such as epinephrine sulfonic acid (ESA) and D-epinephrine, which possess "insignificant therapeutic activity" and thus reduce the product's potency (’876 Patent, col. 1:52-58).
- The Patented Solution: The invention is a pharmaceutical composition that improves the stability of epinephrine by combining it with a specific set of excipients within defined concentration ranges, including a tonicity regulating agent, a pH raising agent, an antioxidant, a pH lowering agent, and a transition metal complexing agent (’876 Patent, Abstract; col. 2:4-24). The specification explains that these components, particularly the pH raising agent, work together to resist pH changes and reduce the degradation of the active ingredient, thereby lowering impurity levels and extending the product's shelf life (’876 Patent, col. 4:1-27).
- Technical Importance: By creating a more stable formulation, the invention provides a more reliable version of epinephrine, a drug the complaint notes has been used for over 100 years for emergency treatment of life-threatening conditions (Compl. ¶20).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶42).
- Claim 1 requires:
- 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 Mar. 29, 2016)
The Invention Explained
- Problem Addressed: The ’657 patent, which shares its specification with the ’876 patent, addresses the same problem of epinephrine instability and degradation in prior art formulations (’657 Patent, col. 1:52-58).
- The Patented Solution: This patent claims methods of using the stable epinephrine composition to treat specific medical conditions. The invention is the act of administering a composition with the particular combination of excipients to a patient for indications including anaphylaxis, bronchospasm, and others (’657 Patent, col. 2:50-53). The complaint alleges that the use of its Adrenalin® product is an embodiment of these method claims (Compl. ¶59).
- Technical Importance: The patent claims methods of using a more stable and potent version of a critical emergency medication, which is intended to ensure reliable treatment for serious conditions like anaphylaxis (Compl. ¶28).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 and dependent claim 20 (Compl. ¶58).
- Claim 1 requires:
- A method of treating a condition comprising administering to a patient in need thereof a composition comprising:
- [A composition with the identical six components and concentration ranges 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, bronchospasm, and sensitivity reactions.
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is "Defendants' Proposed Product," identified as a 30 mg/30 mL vial presentation of Epinephrine Injection, USP, 1 mg/mL (Compl. ¶31).
Functionality and Market Context
- The product is a generic injectable epinephrine solution for which Defendants have submitted a supplemental New Drug Application (sNDA No. 205029) to the FDA seeking marketing approval (Compl. ¶31). The complaint alleges, on information and belief, that the product contains the same active ingredient in the same concentration as Plaintiffs' Adrenalin® product (Compl. ¶45, ¶64).
- The complaint alleges that the label for the proposed product will be "substantially identical" to the label for Adrenalin® and will indicate its use for the "emergency treatment of allergic reactions (Type 1), including anaphylaxis" (Compl. ¶¶ 62-63). The complaint includes the Adrenalin® label as Exhibit C to support its allegations regarding the likely instructions for use of the accused product (Compl. ¶61, Ex. C).
IV. Analysis of Infringement Allegations
U.S. Patent No. 9,119,876 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, | On information and belief, the Proposed Product is a composition comprising each of the claimed ingredients within the claimed concentration ranges. | ¶47 | col. 4:28-34 |
| in the range of about 6 to 8 mg/mL of a tonicity regulating agent, | On information and belief, the Proposed Product is a composition comprising each of the claimed ingredients within the claimed concentration ranges. | ¶47 | col. 8:46-65 |
| in the range of about 2.8 to 3.8 mg/mL of a pH raising agent, | On information and belief, the Proposed Product is a composition comprising each of the claimed ingredients within the claimed concentration ranges. | ¶47 | col. 3:45-48 |
| in the range of about 0.1 to 1.1 mg/mL of an antioxidant, | On information and belief, the Proposed Product is a composition comprising each of the claimed ingredients within the claimed concentration ranges. | ¶47 | col. 5:12-16 |
| in the range of about 0.001 to 0.010 mL/mL of a pH lowering agent, | On information and belief, the Proposed Product is a composition comprising each of the claimed ingredients within the claimed concentration ranges. | ¶47 | col. 8:19-24 |
| and in the range of about 0.01 to 0.4 mg/mL of a transition metal complexing agent, | On information and belief, the Proposed Product is a composition comprising each of the claimed ingredients within the claimed concentration ranges. | ¶47 | col. 7:6-10 |
| wherein the antioxidant comprises sodium bisulfite and/or sodium metabisulfite. | On information and belief, the Proposed Product is a composition comprising each of the claimed ingredients within the claimed concentration ranges, including an antioxidant of sodium bisulfite and/or sodium metabisulfite. | ¶47 | col. 7:1-5 |
- Identified Points of Contention:
- Scope Questions: The term "about" precedes every concentration range in claim 1. A central question will be how the court construes this term, which will define the permissible quantitative deviation from the recited ranges for a finding of literal infringement.
- Technical Questions: The complaint's allegations regarding the composition of the accused product are made "on information and belief" (Compl. ¶47). A primary factual question for the court will be to determine the actual, quantitative composition of Defendants' Proposed Product and compare it to the claimed ranges.
U.S. Patent No. 9,295,657 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: [composition elements as listed in '876 patent chart] | The complaint alleges that Defendants' product label will instruct and encourage medical personnel to administer the product, which on information and belief is the claimed composition, to patients. The complaint references the Adrenalin® label, Exhibit C, which provides instructions for administration (Compl., Ex. C), and alleges the Defendants' label will be substantially identical (Compl. ¶62). | ¶¶58, 63, 66, 67 | col. 4:28-65 |
| wherein the condition is selected from the group consisting of anaphylaxis, bronchospasm, sensitivity reactions, cardiac arrhythmias, GI and renal hemorrhage, superficial bleeding, premature labor, hypoglycemia, | The complaint alleges that the label for Defendants' Proposed Product will state that it is indicated for the "emergency treatment of allergic reactions (Type 1), including anaphylaxis," a condition explicitly recited in the claim. | ¶63 | col. 15:1-6 |
- Identified Points of Contention:
- Scope Questions: As with the ’876 patent, the scope of the term "about" for the composition elements will be critical.
- Technical Questions: The infringement analysis for the ’657 patent depends on the underlying composition meeting the claim limitations. The same factual question regarding the product's precise formulation, as described for the '876 patent, applies here.
- Legal Questions: Infringement of this method claim is predicated on inducement. A key legal question will be whether the final, FDA-approved label for Defendants' product provides instructions that direct or encourage medical professionals to perform the steps of the claimed method, and whether Defendants possessed the requisite intent to induce such infringement (Compl. ¶67).
V. Key Claim Terms for Construction
The Term: "about"
- Context and Importance: This term modifies every concentration range in the asserted independent claims of both patents. Its construction is therefore central to the dispute, as it will determine whether Defendants' formulation literally infringes even if its component concentrations do not fall exactly within the recited numerical ranges. Practitioners may focus on this term because even a small variation in an excipient level could move the product in or out of the scope of literal infringement.
- Intrinsic Evidence for a Broader Interpretation: The specification frequently uses the term "about" when describing preferred concentration ranges, suggesting the inventors did not intend the numbers to be rigid endpoints (e.g., ’876 Patent, col. 4:39-40, "most preferably about 1 mg/mL").
- Intrinsic Evidence for a Narrower Interpretation: The claims recite specific numerical ranges with up to two significant figures (e.g., "2.8 to 3.8 mg/mL"). A party could argue that this precision implies an intent to narrowly define the ranges, and that "about" should only account for minor experimental or measurement variability, not a significant expansion of the claimed scope.
The Term: "pH raising agent"
- Context and Importance: This is a functionally-claimed element central to the patent's asserted solution for stabilizing epinephrine. The complaint alleges Plaintiffs achieved stability by balancing the composition's properties, including those imparted by this agent (Compl. ¶24). Practitioners may focus on this term because the dispute could turn on whether a component in Defendants' product that raises pH also satisfies the more detailed functional requirements described in the specification.
- Intrinsic Evidence for a Broader Interpretation: The specification provides a list of potential compounds that can serve as a pH raising agent, including simple bases like sodium hydroxide as well as salts of various acids (’876 Patent, col. 5:4-11). This suggests the term could be construed broadly to encompass any substance that performs the general function of raising pH.
- Intrinsic Evidence for a Narrower Interpretation: The specification describes the "pH raising agent" as comprising a "buffer system" and may have a pKa within a specific range of the formulation's initial pH (’876 Patent, col. 4:3-12). A party could argue that this language narrows the definition, requiring the agent not merely to be a base but to function as part of a specific type of buffering system as taught in the patent.
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement of infringement of the ’657 method patent, asserting that Defendants' product label will instruct medical personnel to administer the product to treat claimed conditions, such as anaphylaxis (Compl. ¶¶ 63, 67). It also makes conclusory allegations of contributory infringement for both patents, stating the product is a material part of the invention not suitable for substantial non-infringing use (Compl. ¶¶ 50, 70).
- Willful Infringement: Willfulness is alleged based on Defendants' knowledge of the patents, which is inferred from their submission of a Paragraph IV certification to the FDA (Compl. ¶38). Plaintiffs seek enhanced damages for alleged willful and deliberate infringement (Compl., Prayer K, L).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central evidentiary question will be one of compositional identity: What is the precise, quantitative formulation of the Defendants' Proposed Product? The outcome of the case hinges on whether discovery reveals a formulation that falls within the specific compositional limitations of the asserted claims.
- A key legal question will be one of definitional scope: How will the court construe the term "about" as used in the claims? The breadth of this term will directly impact the literal infringement analysis and could be dispositive if the accused formulation's concentrations are close to, but not exactly within, the recited numerical ranges.
- For the method-of-use patent, a critical question will be one of induced infringement: Will the final, FDA-approved label for the accused product contain instructions that are specific enough to encourage medical professionals to administer the product in a manner that directly infringes the asserted method claims, and does the evidence support a finding that Defendants acted with the specific intent to cause that infringement?