PTAB

IPR2022-00657

Fresenius Kabi USA LLC v. Novo Nordisk AS

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Propylene glycol-containing peptide formulations which are optimal for production and for use in injection devices
  • Brief Description: The ’833 patent relates to stable pharmaceutical formulations containing a peptide, specifically a GLP-1 agonist, that use propylene glycol as a tonicity agent. The patent asserts this substitution for other agents, like mannitol, reduces crystallization, deposit formation on production equipment, and clogging of injection needles.

3. Grounds for Unpatentability

Ground 1: Anticipation - Claims 1-15 are anticipated by Flink

  • Prior Art Relied Upon: Flink (International Publication No. WO 03/002136).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Flink disclosed and claimed the exact formulation sought in the ’833 patent. Flink’s claim 14, when read with the specification, disclosed a GLP-1 formulation comprising a buffer, an isotonic agent, and a pH between 7.0 and 10.0. The specification identified “disodium hydrogen phosphate” as a particularly preferred buffer and “propyleneglycol” as one of a small group of suitable isotonic agents. Flink also disclosed the claimed concentration ranges for the GLP-1 agonist and propylene glycol. Petitioner asserted that a person of ordinary skill in the art (POSA) reading Flink’s disclosure of preferred and suitable components would immediately envisage the specific combination recited in the challenged claims.

Ground 2: Obviousness over Flink - Claims 1-15 are obvious over Flink

  • Prior Art Relied Upon: Flink (International Publication No. WO 03/002136).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that if Flink is not found to be anticipatory, any difference between Flink’s disclosure and the challenged claims is a matter of legal technicality, not inventive contribution. The alleged difference would be the express combination of disodium phosphate dihydrate buffer and propylene glycol from Flink’s lists of suitable components.
    • Motivation to Combine: A POSA would combine Flink’s disclosed elements to achieve Flink’s stated goal of a stable GLP-1 formulation. Flink provided a finite list of preferred buffers and suitable isotonic agents, expressly teaching their utility in such formulations. This disclosure provided a clear motivation to select and combine these known, effective components.
    • Expectation of Success: Because Flink taught that both disodium phosphate and propylene glycol were suitable for use in stable GLP-1 formulations, a POSA would have had a reasonable expectation of success in combining them.

Ground 3: Obviousness over Flink in view of Betz - Claims 1-31 are obvious over Flink in view of Betz

  • Prior Art Relied Upon: Flink (International Publication No. WO 03/002136) and Betz (International Publication No. WO 04/004781).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted that Flink’s Example 7 disclosed a formulation containing the specific GLP-1 agonist liraglutide, disodium phosphate dihydrate buffer, and a pH of 7.4, differing from claim 1 only in its use of mannitol as the isotonic agent. Betz taught that replacing mannitol with propylene glycol in peptide formulations improves stability and reduces crystallization.
    • Motivation to Combine: A POSA would combine these references for two primary reasons. First, Flink explicitly taught away from using mannitol in formulations at a pH of 7.4, motivating a POSA to find a substitute. Second, Betz addressed the well-known problem of peptide instability and crystallization by teaching the specific benefits of replacing mannitol with propylene glycol. A POSA would therefore be motivated to modify Flink’s formulation by applying Betz’s teachings to improve stability.
    • Expectation of Success: The substitution of one known isotonic agent (mannitol) for another known isotonic agent (propylene glycol) to achieve a predictable improvement (increased stability and reduced crystallization) represented a routine formulation strategy with a high expectation of success.
    • Key Aspects: This ground extended to the method claims (16-31) by arguing that the recited benefits—reducing deposits and clogging—are the inherent and predictable results of replacing crystallization-prone mannitol with propylene glycol.

4. Key Claim Construction Positions

  • Petitioner argued that the preambles of method claims 23, 26, and 29 (e.g., “[a] method for reducing deposits…”) should be construed as non-limiting statements of purpose. The argument was that these preambles merely state the inherent result of using the claimed formulation and do not add any distinct manipulative steps to the claimed method. For the purposes of the petition, all other terms were proposed to have their plain and ordinary meaning.

5. Arguments Regarding Discretionary Denial

  • Petitioner argued against discretionary denial under both General Plastic and Fintiv precedents.
  • General Plastic: Petitioner asserted this was its first IPR petition against the ’833 patent and that it has no relationship with the petitioners in two prior, settled IPRs (IPR2020-00324 and IPR2020-01252). Therefore, the factors weigh strongly in favor of institution.
  • Fintiv: While a parallel district court litigation involving the ’833 patent was pending (the Sandoz Litigation), Petitioner noted that the Patent Owner was no longer asserting the ’833 patent in that case. Petitioner argued this eliminates any overlap of issues to be decided, making discretionary denial under Fintiv inappropriate.

6. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-31 of Patent 8,114,833 as unpatentable.