PTAB

IPR2025-01346

BPI Labs LLC v. Eli Lilly & Co

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Dual Incretin Peptide Mimetic Compounds
  • Brief Description: The ’780 patent discloses dual incretin peptide mimetic compounds designed to activate receptors for both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). These compounds are intended for treating type 2 diabetes and promoting weight loss.

3. Grounds for Unpatentability

Ground 1: Claims 1-2, 4-7, 9-10, and 12-18 are obvious over Alsina-Fernandez in view of DiMarchi and Lau.

  • Prior Art Relied Upon: Alsina-Fernandez (WO 2011/119657), DiMarchi (WO 2010/011439), and Lau (WO 2006/097537).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that a person of ordinary skill in the art (POSITA) would have systematically modified a lead compound from Alsina-Fernandez using established peptide design strategies taught by DiMarchi and Lau to arrive at the claimed invention.
      • Lead Compound Selection: Petitioner asserted a POSITA would select the peptide from Example 2 of Alsina-Fernandez as a lead compound. This peptide demonstrated the most potent GIP/GLP-1 dual agonist activity and the weakest (most desirable) affinity for the glucagon receptor among the disclosed examples. Furthermore, it avoided PEGylation, a modification strategy known at the time to carry risks of immunogenicity.
      • C-Terminal Modification (DiMarchi): Alsina-Fernandez’s Example 2 compound contained a non-natural C-terminal sequence. Petitioner argued a POSITA would have been motivated to replace this sequence with the well-known exendin C-terminal tail (GGPSSGAPPPS) taught by DiMarchi. This modification was known to enhance GLP-1 receptor potency, improve metabolic stability against DPP-IV degradation, and reduce potential immunogenicity. DiMarchi also taught amidating the C-terminal amino acid to further enhance activity, meeting another limitation of the claims.
      • Half-Life Extension (Lau): The resulting peptide from the Alsina-Fernandez/DiMarchi combination would still have a short half-life, requiring frequent injections. Petitioner contended a POSITA would have been motivated to address this by applying the half-life extension strategy from Lau. Lau, which discloses semaglutide, taught acylating a lysine (K) residue at position 20 with a long-chain fatty acid via a specific hydrophilic spacer (AEEA-AEEA-γGlu). A POSITA would have replaced the arginine at position 20 of the modified Alsina-Fernandez peptide with a lysine (a substitution expressly permitted by DiMarchi) and attached the specific fatty acid and spacer taught by Lau. This would achieve the goal of once-weekly dosing.
      • Resulting Compound: This step-wise combination results in a peptide meeting all structural limitations of independent claim 1, including the specific amino acid substitutions at positions 2 and 13 (from Alsina-Fernandez), the C-terminal amidation (from DiMarchi), and the specific chemical modification at position 20 (from Lau). Dependent claims are met by selecting preferred fatty acid chain lengths (e.g., C18-C20) taught by Lau and DiMarchi.
    • Motivation to Combine: The motivation was presented as a step-wise approach to solving known problems. First, a POSITA would combine Alsina-Fernandez and DiMarchi to optimize potency and metabolic stability while minimizing immunogenicity. Second, to solve the distinct problem of a short therapeutic half-life, the POSITA would further modify the resulting peptide using Lau’s proven strategy for achieving prolonged duration of action suitable for once-weekly dosing. The motivation was rooted in addressing known deficiencies with predictable solutions.
    • Expectation of Success: Petitioner argued a POSITA would have had a high expectation of success because the combination involved applying modular, well-understood, and predictable peptide modification strategies. Each modification was known to reliably impart a specific, desired property (enhanced potency, stability, extended half-life) without disrupting the others, as demonstrated by their successful use in numerous other GLP-1 analogues.

4. Arguments Regarding Discretionary Denial

  • The petition preemptively argued against discretionary denial in view of a co-pending IPR challenging the same patent (IPR2025-01024). Petitioner asserted it is not a real-party-in-interest or privy with respect to the petitioner in the other IPR. It further argued that the ground presented is substantively different because it relies on the teachings of DiMarchi, a reference not cited in the co-pending IPR, thus promoting the integrity of the patent system by allowing a meritorious challenge on different art to proceed.

5. Relief Requested

  • Petitioner requests the institution of an inter partes review and the cancellation of claims 1-2, 4-7, 9-10, and 12-18 of Patent 9,474,780 as unpatentable.