Endo USA 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: Cozen Oconnor
• Case Identification: 1:23-cv-00358, D. Del., 09/09/2024
• Venue Allegations: Venue is alleged to be proper in Delaware based on Defendant's incorporation in the state, its transaction of business within the state, and its history of filing lawsuits in the district.
• Core Dispute: Plaintiff alleges that Defendant’s ready-to-use Vasopressin injection products, intended for treating hypotension, infringe patents related to stable pharmaceutical formulations of vasopressin.
• Technical Context: Vasopressin is a life-saving drug used in critical care settings to treat dangerously low blood pressure; developing formulations with long-term stability is a key challenge for ensuring safe and efficient administration.
• Key Procedural History: This action arises from Defendant Baxter's New Drug Application (NDA) filing with the FDA, which included a Paragraph IV certification alleging that patents related to Plaintiff's VASOSTRICT® product were invalid or would not be infringed. The complaint alleges Baxter had knowledge of the patents-in-suit based on a letter from Plaintiff dated March 29, 2023, and the filing of the original complaint.

Case Timeline

Date	Event
2015-01-30	Earliest Priority Date for ’520, ’265, and ’372 Patents
2018-06-12	U.S. Patent No. 9,993,520 Issues
2021-10-05	U.S. Patent No. 11,135,265 Issues
2021-12-28	U.S. Patent No. 11,207,372 Issues
2023-01-30	Earliest date Baxter sent Paragraph IV Notice Letter to Plaintiffs
2023-03-29	Plaintiffs inform Baxter of Patents-in-Suit; Original Complaint filed
2023-09-23	Baxter receives final FDA approval of its NDA
2024-04-11	Baxter announces launch of its NDA Products
2024-09-09	First Amended 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"

• Patent Identification: U.S. Patent No. 9,993,520, issued on June 12, 2018.

The Invention Explained

• Problem Addressed: The patent’s background section identifies that existing formulations of vasopressin, a critical hormone used to treat low blood pressure, suffer from "poor long-term stability" (’520 Patent, col. 1:24-26).
• The Patented Solution: The invention provides a pharmaceutical formulation of vasopressin designed for enhanced stability and extended shelf life. This is achieved by combining vasopressin with specific components, including an acetate buffer and a preservative (chlorobutanol), and maintaining the solution within a narrow pH range of approximately 3.4 to 3.6 (’520 Patent, Claim 1). The specification provides data suggesting that stability is optimized within this specific pH window (’520 Patent, col. 65:20-25; FIG. 9).
• Technical Importance: A stable, ready-to-use vasopressin formulation can improve patient safety and efficiency in critical care environments by eliminating the need for on-site preparation and reducing the risk of contamination or dosing errors.

Key Claims at a Glance

• The complaint asserts independent claim 1 and dependent claims 4-9 and 13 (Compl. ¶49).
• Independent Claim 1 of the ’520 Patent recites the essential elements of a method for increasing blood pressure:
  • Providing a unit dosage form for intravenous use containing vasopressin, about 1-10 mM acetate buffer, sodium chloride, chlorobutanol, and water.
  • Storing the unit dosage form for at least 12 months, where the form has a pH of about 3.4 to 3.6.
  • After storing, administering the dosage form to a hypotensive human at a specified rate.

U.S. Patent No. 11,135,265 - "Vasopressin Formulations for Use in Treatment of Hypotension"

• Patent Identification: U.S. Patent No. 11,135,265, issued on October 5, 2021.

The Invention Explained

• Problem Addressed: The patent addresses the same technical problem of "poor long-term stability" in vasopressin formulations (’265 Patent, col. 1:24-26).
• The Patented Solution: This invention claims a method of treatment using a "kit" that includes a pre-mixed, ready-to-administer vasopressin formulation contained within a drip-bag (’265 Patent, Claim 1). The formulation itself is stabilized using an acetate buffer and maintaining a specific pH range that varies depending on whether dextrose or sodium chloride is used as a vehicle (’265 Patent, Claim 1).
• Technical Importance: By providing the stable formulation directly in an intravenous drip-bag, the invention streamlines clinical workflow in urgent situations, which may reduce the potential for medication errors associated with preparation.

Key Claims at a Glance

• The complaint asserts independent claim 1 and dependent claims 2-4, 7-14, and 16 (Compl. ¶60).
• Independent Claim 1 of the ’265 Patent recites the essential elements of a method of treatment using a kit:
  • A kit comprising a unit dosage form contained in a drip-bag.
  • The dosage form contains vasopressin, 1-10 mM acetate buffer, a vehicle (dextrose, sodium chloride, or both), and water.
  • The unit dosage form must have a specific pH range (e.g., about 3.7 to 3.9 if the vehicle is sodium chloride).
  • The method includes storing the dosage form for at least 24 hours before administering it to a human via intravenous drip.

U.S. Patent No. 11,207,372 - "Vasopressin Formulations for Use in Treatment of Hypotension"

• Patent Identification: U.S. Patent No. 11,207,372, issued on December 28, 2021 (Compl. ¶17).

Technology Synopsis

This patent also addresses the problem of vasopressin's poor long-term stability (’372 Patent, col. 1:24-26). The claimed solution is a method of increasing blood pressure using a unit dosage form that "consists essentially of" vasopressin, a pH-adjusting agent, and water, stored for at least 30 days at a pH of about 3.5 to 3.7 before administration (’372 Patent, Claim 1).

Asserted Claims

Independent claim 1 and dependent claims 2-3 and 6-13 (Compl. ¶71).

Accused Features

The complaint alleges that Baxter's ready-to-use "Vasopressin in 0.9% Sodium Chloride Injection" products infringe this patent (Compl. ¶36, 71).

III. The Accused Instrumentality

Product Identification

The accused products are Baxter’s "Vasopressin in 0.9% Sodium Chloride Injection" (referred to as "Baxter's NDA Products"), which received FDA approval under NDA No. 217569 (Compl. ¶7, 30).

Functionality and Market Context

• The complaint describes Baxter's product as a "ready-to-use" and "manufacturer-prepared formulation" intended to "increase blood pressure in adults with vasodilatory shock" (Compl. ¶35).
• The products are supplied in bags, with formulations including a 20 units/100 mL strength (0.2 units/mL) (Compl. ¶36). The listed ingredients are vasopressin, sodium chloride, sodium DL-lactate, and water for injection, with pH "adjusted with sodium hydroxide or hydrochloric acid" (Compl. ¶36).
• The product is alleged to have a 24-month shelf life when refrigerated and a 6-month stability at room temperature (Compl. ¶36, 37).
• The complaint alleges that Baxter’s products are marketed as competitors to Plaintiff’s VASOSTRICT® products (Compl. ¶33).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint references an external claim chart (Exhibit F) that was not provided with the pleading; therefore, the infringement theory is summarized below in prose (Compl. ¶49, 60, 71).

U.S. Patent No. 9,993,520 Infringement Allegations

The complaint alleges that Baxter's method of making, using, and selling its NDA Products infringes at least claim 1 of the ’520 patent (Compl. ¶49). The theory appears to be that Baxter provides a unit dosage form (its pre-mixed bags) that contains vasopressin and other ingredients which allegedly meet the claim limitations (Compl. ¶36). This product is then stored for an extended period (up to 24 months) and subsequently administered to hypotensive patients, thereby performing the steps of the claimed method (Compl. ¶35, 37).

U.S. Patent No. 11,135,265 Infringement Allegations

The complaint alleges that Baxter's activities infringe at least claim 1 of the ’265 patent (Compl. ¶60). The infringement theory suggests that Baxter's product, a pre-mixed formulation of vasopressin sold in a drip-bag, constitutes the "kit" recited in the claims (Compl. ¶36). The complaint states the product contains vasopressin in a sodium chloride solution, and alleges this formulation meets the claimed compositional and pH requirements (Compl. ¶36). The commercial life cycle of the product—from manufacture and storage to clinical administration via intravenous drip—is alleged to map onto the claimed method steps (Compl. ¶35, 37).

Identified Points of Contention

• Scope Question ('520 and '265 Patents): Both asserted independent claims require an "acetate buffer." The complaint identifies "sodium DL-lactate" as an ingredient in the accused product (Compl. ¶36). This raises the question of whether a lactate-containing compound can be construed to meet the "acetate buffer" limitation, either literally or under the doctrine of equivalents.
• Factual Question ('520 and '265 Patents): The asserted claims recite specific pH ranges (e.g., "about 3.4 to 3.6" in the ’520 patent; "about 3.7 to 3.9" in the ’265 patent). The complaint alleges that the accused product's pH "may have been adjusted" but does not plead a specific final pH value (Compl. ¶36). A central evidentiary dispute may be whether the accused products, as sold, actually have a pH that falls within the claimed ranges.
• Factual Question ('520 Patent): Claim 1 of the ’520 patent explicitly requires "chlorobutanol." The complaint's description of the accused product's formulation does not list chlorobutanol as an ingredient (Compl. ¶36). This discrepancy suggests a potential point of non-infringement that may be a focus of the litigation.

V. Key Claim Terms for Construction

• The Term: "acetate buffer" (asserted in independent claim 1 of both the ’520 and ’265 Patents)

• Context and Importance: This term is central to the dispute because the accused product is alleged to contain "sodium DL-lactate," not an acetate compound (Compl. ¶36). The infringement determination for both lead patents could hinge on whether "acetate buffer" is construed to encompass lactate-based compounds.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: A party arguing for broader scope may point to the specification's general focus on pH control for stability as the purpose of a buffer, suggesting that other pharmaceutically acceptable buffers performing the same function should be included.
  • Evidence for a Narrower Interpretation: The claim language uses the specific chemical term "acetate." The specification provides examples of formulations using sodium acetate (’265 Patent, Table 51). This may support an argument that the inventors intentionally limited the claim scope to buffers derived from acetic acid and did not claim the broader functional class of all possible pH buffering agents.

• The Term: "about" (qualifying the pH ranges in the asserted claims, e.g., "a pH of from about 3.4 to 3.6" in ’520 Patent, Claim 1)

• Context and Importance: The patents describe stability as being highly dependent on pH, with specific ranges identified as optimal. The term "about" introduces ambiguity to these boundaries. If the accused product's pH is measured to be close to but not strictly within the recited numerical range (e.g., 3.7), the construction of "about" will be dispositive.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The specification includes graphs showing stability across various pH values, which could be used to argue that "about" should be interpreted functionally to include any pH that provides a comparable stability profile to the recited range (’520 Patent, FIG. 9).
  • Evidence for a Narrower Interpretation: A party could argue that the inventors selected these precise ranges because they correspond to a peak in stability, as suggested by the data (’520 Patent, col. 65:20-25). This would support a narrow construction where "about" only accounts for standard scientific measurement tolerances rather than materially extending the range.

VI. Other Allegations

• Indirect Infringement: The complaint alleges both induced and contributory infringement. The inducement allegation is based on Baxter's alleged knowledge of the patents and its encouragement of infringement, presumably through product labels and instructions directing clinicians to perform the patented methods of administration (Compl. ¶47, 58, 69). The contributory infringement allegation is based on the assertion that Baxter's products are especially adapted for the infringing use of treating hypotension and have no substantial non-infringing use (Compl. ¶48, 59, 70).
• Willful Infringement: Willfulness is alleged for all three patents-in-suit (Compl. ¶52, 63, 74). The complaint alleges pre-suit knowledge based on Baxter’s Paragraph IV certification for related patents and, more directly, a letter from Plaintiffs dated March 29, 2023, that specifically identified the patents-in-suit. Continued alleged infringement after receiving this notice forms the basis of the willfulness claim (Compl. ¶39, 41).

VII. Analyst’s Conclusion: Key Questions for the Case

• A core issue will be one of chemical scope: can the term "acetate buffer," as claimed in the patents, be construed to read on the "sodium DL-lactate" formulation of the accused product, either literally or through the doctrine of equivalents?
• A second central issue will be one of factual proof: what is the actual pH of Baxter’s commercially available vasopressin products, and does that pH fall within the specific numerical ranges qualified by the term "about" in the asserted claims?
• A third key question will be one of evidentiary completeness: does the accused product contain "chlorobutanol," an express element of claim 1 of the ’520 patent, and what evidence will be presented to resolve the discrepancy between the claim requirement and the product's listed ingredients?