DCT
1:23-cv-01412
Par Pharmaceutical Inc v. Long Grove Pharma LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Par Pharmaceutical, Inc. (New York); Par Sterile Products, LLC (Delaware); Endo Par Innovation Company, LLC (Delaware)
- Defendant: Long Grove Pharmaceuticals, LLC (Delaware)
- Plaintiff’s Counsel: Cozen O'Connor
- Case Identification: 1:23-cv-01412, D. Del., 12/08/2023
- Venue Allegations: Venue is asserted based on the Defendant being a Delaware limited liability company that maintains a registered agent and conducts business in the state.
- Core Dispute: Plaintiffs allege that Defendant's submission of a New Drug Application to the FDA for generic vasopressin injection products constitutes an act of infringement of two patents covering stable, ready-to-use formulations of vasopressin for treating hypotension.
- Technical Context: Vasopressin is a life-saving drug used in critical care to treat vasodilatory shock, but its chemical instability in liquid form presents a challenge for creating products with a practical shelf-life.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant's submission of New Drug Application (NDA) No. 217766. The complaint notes that on or after September 22, 2023, Defendant sent a Paragraph IV Certification notice concerning other patents in the same family. Plaintiffs allege they subsequently informed Defendant of the patents-in-suit during settlement discussions, a fact that may be relevant to the willfulness allegations.
Case Timeline
| Date | Event |
|---|---|
| 2012-09-25 | JHP Pharmaceuticals (Plaintiff's predecessor) submits NDA for VASOSTRICT® |
| 2014-04-17 | FDA approves VASOSTRICT® NDA No. 204485 |
| 2015-01-30 | Earliest Priority Date for '520 and '372 Patents |
| 2018-06-12 | U.S. Patent No. 9,993,520 issues |
| 2021-12-28 | U.S. Patent No. 11,207,372 issues |
| 2023-09-22 | Defendant sends Paragraph IV Notice Letter regarding related patents |
| 2023-12-08 | Complaint filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,993,520 - "Vasopressin Formulations for Use in Treatment of Hypotension"
The Invention Explained
- Problem Addressed: The patent addresses the "poor long-term stability" of existing vasopressin formulations, which complicates their use in emergency clinical settings where a patient's blood pressure drops precipitously ('520 Patent, col. 1:19-21, col. 7:22-26).
- The Patented Solution: The invention provides a stable, ready-to-use liquid formulation of vasopressin. Stability is achieved by controlling several factors, most notably maintaining the formulation within a narrow, acidic pH range of 3.4 to 3.8 and using an acetate buffer, which limits the degradation of the active peptide ingredient over time ('520 Patent, Abstract; col. 8:32-41; col. 175:59-62).
- Technical Importance: Developing a stable, pre-mixed injectable vasopressin formulation eliminates the need for reconstitution at the point of care, thereby reducing preparation time and potential for error in critical medical situations (Compl. ¶18).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 ('520 Patent, col. 175:28-62; Compl. ¶38-39).
- The essential elements of Claim 1 are:
- A method of increasing blood pressure in a hypotensive human.
- The method involves providing a unit dosage form comprising (i) a specific concentration of vasopressin, (ii) an acetate buffer, (iii) a low level of degradation products, (iv) sodium chloride, and (v) water, with a pH of 3.4 to 3.8.
- The method includes a step of storing the dosage form for at least 24 hours.
- The method concludes with administering the dosage form intravenously at a specified rate.
- The complaint alleges infringement of "one or more claims" of the patent (Compl. ¶35).
U.S. Patent No. 11,207,372 - "Vasopressin Formulations for Use in Treatment of Hypotension"
The Invention Explained
- Problem Addressed: Like its parent, the '372 patent addresses the challenge of creating vasopressin formulations with sufficient long-term stability for clinical use ('372 Patent, col. 1:23-25).
- The Patented Solution: The patent discloses a stable liquid vasopressin formulation defined by a list of essential ingredients. The asserted claim uses the transitional phrase "consists essentially of," which defines the formulation by what it contains while implicitly excluding other ingredients that would materially affect the invention's stability. The formulation specifies vasopressin, a pH-adjusting agent, an acetate buffer, sodium chloride, and water, maintained at a pH of 3.5 to 3.7 ('372 Patent, col. 173:18-32).
- Technical Importance: This patent claims a specific combination of ingredients intended to provide a stable, ready-to-use therapeutic for treating life-threatening hypotension, improving safety and efficiency in critical care settings (Compl. ¶18; '372 Patent, col. 1:15-22).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 ('372 Patent, col. 173:18-43; Compl. ¶50-51).
- The essential elements of Claim 1 are:
- A method of increasing blood pressure in a human.
- The method involves providing a unit dosage form that consists essentially of: (a) a specific concentration of vasopressin, (b) a pH-adjusting agent, (c) an acetate buffer, (d) about 0.9% NaCl, and (e) water.
- The dosage form has a pH of 3.5 to 3.7.
- The method includes steps of storing the dosage form for at least 24 hours and subsequently administering it intravenously.
- The complaint alleges infringement of "one or more claims" of the patent (Compl. ¶47).
III. The Accused Instrumentality
Product Identification
The accused products are Long Grove's "Vasopressin Injection, 0.2 Unit/mL, 0.4 Unit/mL, 1.0 Unit/mL," which are the subject of New Drug Application No. 217766 submitted to the FDA (Compl. ¶8, ¶24).
Functionality and Market Context
The products are injectable formulations of vasopressin intended for increasing blood pressure in adults with vasodilatory shock, the same indication as Plaintiffs' VASOSTRICT® product (Compl. ¶23). The complaint alleges that Long Grove's submission of its NDA for a product that will compete with VASOSTRICT® is an act of infringement under 35 U.S.C. § 271(e)(2) (Compl. ¶26, ¶35).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint makes general allegations that Long Grove's NDA Products will meet all limitations of the asserted claims. The analysis below reflects these allegations, which will be tested through discovery of Long Grove's confidential NDA submission.
'520 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of increasing blood pressure in a human in need thereof... | The intended use of the Long Grove NDA Products is to increase blood pressure in hypotensive patients. | ¶39 | col. 7:22-26 |
| a) providing a unit dosage form for intravenous administration, wherein the unit dosage form comprises: i) from about 0.1 units/mL to about 1 unit/mL of vasopressin... | The complaint alleges the Long Grove NDA Products are provided in unit dosage forms with a vasopressin concentration within the claimed range. | ¶8, ¶39 | col. 8:54-57 |
| ii) from about 1 mM to about 10 mM acetate buffer; | The Long Grove NDA Products are alleged to be formulated with an acetate buffer within the claimed concentration range. | ¶39 | col. 52:2-4 |
| iii) 0-2% vasopressin degradation products; | The Long Grove NDA Products are alleged to be stable formulations with degradation products within the claimed percentage. | ¶39 | col. 2:5-9 |
| b) storing the unit dosage form for at least about 24 hours... | The complaint alleges the method of use for the Long Grove NDA Products will involve storing the product for at least 24 hours prior to administration. | ¶39 | col. 10:1-3 |
| c) after the storing, administering the unit dosage form to the human by intravenous administration...wherein: the unit dosage form has a pH of 3.4 to 3.8... | The Long Grove NDA Products are alleged to be administered intravenously and to have a pH within the claimed range. | ¶39 | col. 175:59-62 |
'372 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of increasing blood pressure in a human in need thereof... | The intended use of the Long Grove NDA Products is to increase blood pressure in hypotensive patients. | ¶51 | col. 7:27-31 |
| providing a unit dosage form, wherein the unit dosage form consists essentially of: a) from about 0.1 units/mL to about 1 unit/mL of vasopressin... b) a pH-adjusting agent; c) an acetate buffer; d) about 0.9% NaCl; and e) water; | The complaint alleges that the formulation in the Long Grove NDA consists essentially of the five recited components. | ¶51 | col. 1:45-53 |
| wherein the unit dosage form has a pH of from about 3.5 to about 3.7... | The Long Grove NDA Products are alleged to have a pH within the narrowly claimed range. | ¶51 | col. 1:54-55 |
| storing the unit dosage form for at least about 24 hours... | The complaint alleges the method of use for the Long Grove NDA Products will involve storing the product for at least 24 hours prior to administration. | ¶51 | col. 1:55-58 |
| after the storing, intravenously administering the unit dosage form to the human... | The complaint alleges the Long Grove NDA Products are for intravenous administration. | ¶51 | col. 1:59-60 |
Identified Points of Contention
- Factual Mismatch: The core of the dispute will depend on the specifics of Long Grove's NDA, which are not public. A primary question is whether the accused formulation's exact components, concentrations, and pH fall within the ranges claimed in the '520 and '372 patents.
- Scope Questions ('372 Patent): The use of "consists essentially of" in the '372 patent raises a key question: Does the accused product contain any unlisted ingredients or excipients? If so, the court will need to determine whether those unlisted ingredients materially alter the basic and novel properties of the claimed invention, namely its stability.
V. Key Claim Terms for Construction
The Term: "consists essentially of" ('372 Patent, Claim 1)
Context and Importance: This term is legally distinct from "comprising" and is central to the scope of the '372 patent. Infringement will turn on whether any unlisted ingredients in Long Grove's product are found to materially affect the formulation's stability, which the patent identifies as its key characteristic ('372 Patent, Abstract). Practitioners may focus on this term because it creates a high bar for infringement if the accused product includes additional functional excipients.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party might argue that only excipients that negatively impact stability are excluded, pointing to the patent's goal of achieving stability ('372 Patent, col. 1:23-25).
- Evidence for a Narrower Interpretation: The patent lists numerous potential excipients and buffers but the claim recites a very specific combination ('372 Patent, col. 56:1-66). A party could argue that the choice to use "consists essentially of" with a short list of ingredients was a deliberate decision to exclude any other components that have any stabilizing or destabilizing effect.
The Term: "acetate buffer" ('520 Patent, Claim 1; '372 Patent, Claim 1)
Context and Importance: The buffer is identified as a key component for achieving the claimed stability at the specified pH. The definition of this term will be critical to determining if Long Grove's formulation, which may use a different buffering system or a combination of agents, meets this limitation.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification lists acetate as one of several "examples of buffers that can be used" ('520 Patent, col. 56:32-37), which may support an argument that the term encompasses various acetate-based buffering systems.
- Evidence for a Narrower Interpretation: The claims recite specific concentration ranges (e.g., 1 mM to 10 mM in '520 Claim 1). Further, the examples focus heavily on the performance of acetate ('520 Patent, Example 4, col. 66:6-12), which could be used to argue the term is limited to formulations where acetate is the primary or sole buffering agent.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for both patents. The basis for inducement is the allegation that Long Grove's product labeling and instructions will encourage medical professionals to administer the drug in a manner that directly infringes the method claims (Compl. ¶36, ¶48). The basis for contributory infringement is the allegation that the accused products are especially adapted for the infringing use and have no substantial non-infringing use (Compl. ¶37, ¶49).
- Willful Infringement: The complaint alleges willful infringement based on Defendant's knowledge of the patents-in-suit. This knowledge is alleged to have come from "settlement discussions" that occurred after Defendant sent its Paragraph IV notice on related patents and, additionally, from the filing of the complaint itself (Compl. ¶30, ¶42, ¶54). The allegation of pre-suit knowledge from specific discussions, if proven, could strengthen the willfulness claim.
VII. Analyst’s Conclusion: Key Questions for the Case
- Formulation Match: The central question is factual: does the precise formulation disclosed in Long Grove’s confidential New Drug Application—specifically its ingredients, concentrations, pH, and stability profile—literally fall within the boundaries of the asserted claims of the '520 and '372 patents?
- Scope of "Consists Essentially Of": A critical legal and factual issue for the '372 patent will be whether Long Grove’s product contains any unlisted components. If it does, the case may turn on whether those components are deemed to "materially affect the basic and novel properties" of the patented formulation, thereby avoiding infringement of the more restrictive "consists essentially of" claim.
- Basis for Willfulness: A key question for potential enhanced damages will be the timing and substance of Defendant's knowledge. The court will examine whether Plaintiffs can establish that Long Grove was aware of the specific patents-in-suit before the litigation began, as alleged based on settlement discussions, and whether its continued pursuit of its NDA in the face of that knowledge constituted egregious conduct.