Amneal Pharmaceuticals Inc v. Nivagen Pharmaceuticals Inc

1. Case Identification

• Case #: IPR2025-00779
• Patent #: 11,813,291
• Filed: April 11, 2025
• Petitioner(s): Amneal Pharmaceuticals, Inc.
• Patent Owner(s): Nivagen Pharmaceuticals, Inc.
• Challenged Claims: 1, 3-11, 14-15, and 17-20

2. Patent Overview

• Title: Ready-to-Use Potassium Phosphates in Sodium Chloride Solution
• Brief Description: The ’291 patent describes stable, isotonic, sterile, ready-to-use (RTU) aqueous potassium phosphate solutions for treating hypophosphatemia. The key features of the claimed solutions are specific concentrations of phosphorus and potassium, the inclusion of sodium chloride, and a low aluminum content (less than 50 mcg/L).

3. Grounds for Unpatentability

Ground 1: Obviousness over the CMP Art, Terlevich, and Perks, optionally in view of Ogawa - Claims 1, 3-9, 11, and 17-20 are obvious over the combination of these references.

• Prior Art Relied Upon: CMP Art (International Publication No. WO 2020/081118 (“CMP-PCT”) and its corresponding FDA Drug Label (“CMP-FDA”)), Terlevich (a 2003 journal article), Perks (a 2017 journal article), and Ogawa (a 2013 journal article).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the prior art collectively disclosed all limitations of the challenged claims. CMP-PCT taught a concentrated sterile potassium phosphate composition designed for stability and low particulate matter, which served as the base formulation. However, CMP-PCT’s solution required dilution before administration. Terlevich and Perks taught that concentrated phosphate solutions were routinely diluted by hospital pharmacies into RTU solutions, specifically disclosing concentrations within the range of 3 to 15 mmol/100 mL of phosphate. Petitioner contended that adapting the CMP-PCT concentrate to the 15 mmol/100 mL phosphorus concentration taught by Perks was an obvious step to create a convenient RTU product. The use of 0.9% sodium chloride as a tonicity agent to make the solution isotonic was taught by CMP-FDA for its diluted solutions and was a well-known practice. Regarding the low aluminum limitation (≤50 mcg/L), Petitioner asserted that CMP-PCT already taught using ultra-low levels of aluminum (realizing 200-300 mcg/L) and that Ogawa explicitly taught that aluminum levels should be below 50 ppb (50 mcg/L) to prevent particle precipitation in phosphate solutions. The stability and packaging claims (e.g., storage in a polyolefin container) were allegedly met by Terlevich, which disclosed a commercially successful RTU phosphate product packaged in a semi-rigid polyethylene container.
  • Motivation to Combine: A person of ordinary skill in the art (POSITA) would combine these references to improve patient safety and convenience. A POSITA would be motivated to convert the concentrated, stable solution of CMP-PCT into an RTU format, as taught by Terlevich and Perks, to eliminate the need for bedside dilution, thereby reducing calculation errors and contamination risk. The motivation to incorporate Ogawa’s teaching was to solve the known problem of aluminum-induced particle formation in phosphate solutions, thereby increasing product safety and shelf life. A POSITA would look to the packaging solutions in Terlevich to ensure the stability of the final RTU product.
  • Expectation of Success: Petitioner argued a POSITA would have a high expectation of success. Creating RTU solutions by diluting concentrates was a routine and predictable practice in pharmacology. The stability of the resulting solution was expected, as the base components from CMP-PCT were already stable, and the packaging from Terlevich was proven for similar products. Likewise, achieving low aluminum levels by sourcing low-aluminum raw materials, as suggested by Ogawa, was a straightforward and well-understood method.

Ground 2: Obviousness over the Ground 1 Art in view of Nevakar - Claims 9-11, 14-15, and 17-20 are obvious over the combination of these references.

• Prior Art Relied Upon: The combined teachings of the art from Ground 1, further in view of Nevakar (Application # 2019/0290602).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground specifically addressed claims requiring packaging in a flexible container of a certain volume (e.g., 100 mL) and the use of a secondary metallized overwrap. While the Ground 1 art provided the RTU solution, Petitioner argued Nevakar supplied the missing packaging elements. Nevakar explicitly disclosed packaging storage-stable, RTU compositions in flexible IV bags, including polyolefin bags, with volumes between 100 mL and 1,000 mL. Furthermore, Nevakar taught that these flexible bags could be "further enclosed in a metallized over-container" (e.g., an aluminum foil pouch) to protect the solution from degradation by preventing evaporation and oxygen penetration. This teaching directly mapped onto the limitations of claims requiring a flexible polyolefin container (claim 9), a secondary metallized overwrap (claims 10 and 15), and a 100 mL volume (claims 9 and 14).
  • Motivation to Combine: A POSITA, having developed the RTU solution from the Ground 1 art, would be motivated to use the well-known and commercially available packaging solutions taught by Nevakar. The primary motivation was to ensure long-term stability, a key objective also found in the primary reference, CMP-PCT. Nevakar's multi-layered containers and metallized overwraps were known to provide superior moisture and gas barriers, making them an obvious choice for packaging a sensitive RTU parenteral solution intended for extended storage.
  • Expectation of Success: Success would be reasonably expected because packaging a liquid pharmaceutical into a standard flexible IV bag system, as described by Nevakar, is a simple, common, and highly predictable manufacturing step. There was no technical challenge or unpredictability in placing the RTU solution from Ground 1 into the container taught by Nevakar.

4. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under §314(a) based on Fintiv factors was unwarranted. It asserted that the co-pending district court litigation was in its earliest stages, with no scheduling order entered, no discovery conducted, and no trial date set. Petitioner further noted that the presiding judge grants over 70% of motions to stay pending inter partes review (IPR) and that any trial would occur well after a Final Written Decision (FWD) in this proceeding. To further weigh against denial, Petitioner made a Sotera stipulation, agreeing not to pursue in the litigation any invalidity grounds raised or reasonably could have been raised in the IPR if instituted.

5. Relief Requested

• Petitioner requests institution of an IPR and cancellation of claims 1, 3-11, 14-15, and 17-20 of Patent 11,813,291 as unpatentable.