PTAB

IPR2025-00731

Amneal Pharmaceuticals, Inc. v. Nivagen Pharmaceuticals, Inc.

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1. Case Identification

2. Patent Overview

  • Title: Ready-to-Use Potassium Phosphates Solutions
  • Brief Description: The ’661 patent relates to sterile, ready-to-use (RTU) aqueous potassium phosphate solutions for phosphorus replacement therapy. The invention claims specific formulations having a phosphorus concentration between 1.5 and 15 mmol/100 mL, a potassium concentration of no more than 22 mEq/100 mL, and an aluminum content of less than 50 mcg/L, intended for stable storage and direct administration.

3. Grounds for Unpatentability

Ground 1: Anticipation and Obviousness of Claims 1-20 over Nivagen-1

  • Prior Art Relied Upon: Nivagen-1 (Application # 2022/0110969).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Nivagen-1, which is the parent application of the ’661 patent, qualifies as prior art under 35 U.S.C. §102(a)(1) because the ’661 patent is not entitled to its earlier priority date. Petitioner asserted that Nivagen-1 discloses every limitation of the challenged claims. Specifically, Nivagen-1 taught a sterile RTU potassium phosphate solution with sodium chloride, a phosphorus concentration of 15 mmol/100 mL (the upper limit of the claimed range), an aluminum level below 50 mcg/L, and a pH between 6.2 and 6.8. For dependent claims, Nivagen-1 allegedly disclosed the required phosphate ratios, component amounts, stability profiles after autoclaving, and packaging in flexible multilayer polyolefin containers, thereby anticipating or, at a minimum, rendering obvious all challenged claims.
    • Key Aspects: The success of this ground is entirely dependent on Petitioner's argument, detailed in Section 5 below, that the ’661 patent lacks written description support in its priority application, making its effective filing date September 5, 2023, and thus rendering the earlier-published Nivagen-1 prior art.

Ground 2: Obviousness over CMP Art and Terlevich - Claims 1-8, 11-13, and 17-20 are obvious over the CMP Art in view of Terlevich, optionally in view of Ogawa.

  • Prior Art Relied Upon: The CMP Art (International Application # WO2020/081118 (“CMP-PCT”) and its corresponding FDA Drug Label), Terlevich (2003 journal article), and optionally Ogawa (2013 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted that CMP-PCT disclosed a stable, concentrated potassium phosphate solution that required dilution before use. Terlevich described a widely used, commercially available RTU potassium phosphate solution (Phosphate Polyfusor) for treating the same condition, hypophosphatemia. The RTU solution in Terlevich had a phosphate concentration of 10 mmol/100 mL. Petitioner argued it would have been obvious to dilute the CMP-PCT concentrate (300 mmol/100 mL) by a factor of 30 to achieve the known, effective RTU concentration taught by Terlevich. This simple dilution would result in a formulation meeting the ’661 patent’s claimed ranges for phosphorus, potassium, and phosphate ratios. The optional addition of Ogawa, which taught that aluminum levels as low as 50 ppb (50 mcg/L) can cause particle formation in phosphate solutions, would have guided a POSITA to achieve the claimed low aluminum levels.
    • Motivation to Combine: A POSITA would combine the teachings to leverage the benefits of both references: creating a convenient, safer RTU product based on the stable, low-particulate formulation of CMP-PCT. The known clinical benefits of RTU solutions, such as ease of use and reduction of calculation errors, as taught by Terlevich, provided a strong motivation. The FDA-mandated use of saline to dilute the CMP product further motivated the inclusion of sodium chloride.
    • Expectation of Success: A POSITA would have had a high expectation of success, as creating an RTU solution from a concentrate was a routine and predictable process. The combination involved simple dilution and the use of well-known excipients to achieve a formulation with known, desirable properties.

Ground 3: Obviousness over Ground 2 Art and Nevakar - Claims 9-20 are obvious over the Ground 2 Art in view of Nevakar.

  • Prior Art Relied Upon: The prior art combination from Ground 2, further in view of Nevakar (Application # 2019/0290602).
  • Core Argument for this Ground:
    • Prior Art Mapping: While the Ground 2 art taught the RTU solution, Petitioner argued that Nevakar taught the specific packaging limitations recited in claims 9-10 and 14-16. Nevakar explicitly disclosed storing stable, RTU pharmaceutical compositions in flexible IV bags, including flexible multilayer polyolefin bags, with volumes between 100 mL and 1,000 mL. Nevakar further taught enclosing these primary containers in a secondary metallized overwrap to enhance stability by preventing moisture and gas permeation. These teachings directly map onto the unclaimed packaging elements.
    • Motivation to Combine: A POSITA, having formulated the RTU solution from the Ground 2 art, would have been motivated to use the advanced, stability-enhancing packaging taught by Nevakar. Protecting a parenteral solution from degradation, evaporation, and oxygen ingress using multilayer bags and overwraps was a known strategy to ensure long-term shelf life, a key goal also expressed in the CMP-PCT reference.
    • Expectation of Success: Packaging a standard RTU solution in a well-known, commercially available container system like that described in Nevakar was a straightforward implementation. It represented a simple substitution of one known container type for another to achieve a predictable improvement in stability.

4. Key Technical Contentions (Beyond Claim Construction)

  • Priority Date Challenge: Petitioner's primary technical-legal argument was that the ’661 patent is not entitled to the filing date of its parent (’001 application) or its provisional application.
    • Petitioner contended that the challenged claims, all requiring a phosphorus concentration range of 1.5 mmol/100 mL to 15 mmol/100 mL, lack written description support under §112 in the priority documents.
    • The argument was that the priority applications only disclosed a single, specific RTU phosphate concentration of 15 mmol/100 mL. The lower limit of the claimed range (1.5 mmol/100 mL) was allegedly new matter introduced for the first time in the application that issued as the ’661 patent.
    • Based on this, Petitioner asserted the effective filing date for all challenged claims is the actual filing date of September 5, 2023, not the earlier claimed priority date.

5. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial of institution would be improper.
  • Regarding §314(a) (Fintiv Factors): The parallel district court litigation was in its infancy. No scheduling order had been entered, no trial date was set, and no significant discovery had occurred. Petitioner noted that the assigned judge has a high rate of granting stays pending IPR, and the average time to trial is three years, meaning a Final Written Decision (FWD) in this IPR would issue long before any potential trial.
  • Sotera Stipulation: Petitioner stipulated that if the IPR is instituted, it will not pursue in litigation any ground that was raised, or reasonably could have been raised, in the petition.
  • Regarding §325(d): Petitioner argued denial would be improper because its grounds rely on prior art (specifically Nivagen-1 and the CMP Art) that was not substantively considered by the Examiner during prosecution of the ’661 patent.

6. Relief Requested

  • Petitioner requested the institution of an inter partes review and cancellation of claims 1-20 of Patent 11,925,661 as unpatentable.