PTAB

IPR2025-01346

BPI Labs, LLC v. Eli Lilly & Co.

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1. Case Identification

2. Patent Overview

  • Title: Dual Incretin Peptide Mimetic Compounds
  • Brief Description: The ’780 patent is directed to dual incretin peptide mimetic compounds that agonize receptors for both human glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). The compounds are intended for treating type 2 diabetes and promoting weight loss, and are described as having a "balanced" co-agonism, stability against deactivation by DPP-IV, and suitability for once-weekly dosing.

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: Petitioner argued that the challenged claims are an obvious combination of known elements from the prior art to achieve predictable results. The argument centered on a three-step modification of a lead compound from Alsina-Fernandez using well-understood design strategies taught by DiMarchi and Lau.
    • Prior Art Mapping:
      • Step 1: Selecting Alsina-Fernandez as a Lead Compound. Petitioner asserted that a person of ordinary skill in the art (POSA) would have selected the peptide from Example 2 of Alsina-Fernandez as a lead compound. This peptide was disclosed as a potent GIP/GLP-1 co-agonist with desirable selectivity (i.e., weak binding) for the glucagon receptor. Petitioner argued this compound represented a promising starting point for developing an improved therapeutic for diabetes and weight loss, addressing the known side effects (like nausea) of selective GLP-1 agonists.
      • Step 2: Modifying with DiMarchi for Potency and Reduced Immunogenicity. A POSA would have been motivated to modify the C-terminus of the Alsina-Fernandez peptide based on the teachings of DiMarchi. The lead compound's C-terminus included unnatural amino acids (e.g., Aib at position 29), which were known to increase the risk of immunogenicity. DiMarchi taught replacing the C-terminus with the well-known exenatide C-terminal tail (GPSSGAPPPS) and a terminal amide group to enhance GLP-1 receptor potency, improve metabolic stability, and reduce immunogenicity by using naturally occurring amino acids. This modification was a known strategy for improving peptide drug candidates.
      • Step 3: Modifying with Lau for Extended Half-Life. The resulting peptide from the first two steps would still have a short half-life, requiring frequent injections. Petitioner argued a POSA would have been motivated to further modify the peptide to achieve once-weekly dosing, a known goal in the field. Lau, which discloses the basis for semaglutide, taught a specific strategy for prolonging half-life: acylating a lysine (K) residue at position 20 with a lipophilic moiety. This involved attaching a fatty acid (e.g., C16, C18, or C20) via a specific hydrophilic spacer ([2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)). A POSA would have applied this established albumin-binding strategy to the peptide, which involved substituting the native arginine (R) at position 20 with a lysine (K) (an option explicitly provided by DiMarchi) and then attaching the spacer and fatty acid as taught by Lau.
    • Motivation to Combine: The motivation was to systematically improve a promising lead GIP/GLP-1 co-agonist (Alsina-Fernandez) by applying known, modular design strategies to achieve predictable and desirable outcomes. The goals were to enhance potency and reduce immunogenicity (taught by DiMarchi) and to significantly extend the half-life for improved patient compliance via weekly dosing (taught by Lau). These were well-recognized objectives in the field of peptide therapeutic development.
    • Expectation of Success: Petitioner asserted a POSA would have had a high and reasonable expectation of success. Each modification was a rational, well-documented strategy with a known purpose and predictable effect. The use of an exenatide tail to improve stability and the acylation of peptides with fatty acids to prolong half-life were established techniques that had been successfully implemented in other FDA-approved drugs.

4. Arguments Regarding Discretionary Denial

  • Petitioner contended that discretionary denial would be inappropriate. The petition acknowledged a co-pending inter partes review (IPR), IPR2025-01024, filed by a different petitioner against the same ’780 patent. However, Petitioner asserted it is neither a real-party-in-interest nor a privy with respect to the earlier proceeding. Crucially, Petitioner argued that the grounds are substantively different because the instant petition relies on the teachings of DiMarchi, a reference not cited in the co-pending IPR.

5. Relief Requested

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