PTAB

IPR2015-00990

Coalition for Affordable Drugs II LLC v. NPS Pharmaceuticals Inc

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Key Events
Petition

1. Case Identification

2. Patent Overview

  • Title: GLP-2 Formulations
  • Brief Description: The ’886 patent relates to stable, lyophilized pharmaceutical formulations containing glucagon-like peptide-2 (GLP-2) or its analogs. The challenged claims are directed to the formulations themselves, kits containing the formulations along with sterile water for reconstitution, and methods of using the formulations to treat gastrointestinal disorders.

3. Grounds for Unpatentability

Ground 1: Obviousness of Formulation/Method Claims - Claims 46-50, 52, and 69-74 are obvious over Drucker ’379 in view of Kornfelt and Osterberg.

  • Prior Art Relied Upon: Drucker ’379 (Patent 5,789,379), Kornfelt (Patent 5,652,216), and Osterberg (a 1999 European Journal of Pharmaceutical Sciences article).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Drucker ’379 disclosed the core elements of the invention: a pharmaceutical formulation containing a GLP-2 analog in a medically useful amount (0.1 to 50 mg/ml) within a phosphate buffer for treating gastrointestinal diseases. However, peptide formulations were known to be unstable. Kornfelt and Osterberg addressed this known problem for glucagon—a structurally and functionally similar peptide—by teaching the use of L-histidine as a stabilizing agent and mannitol or sucrose as bulking agents to create stable, lyophilized formulations. Petitioner asserted that the combination of these references taught every limitation of independent claims 46, 52 (formulations), and 69 (methods of treatment), including the specific concentrations and pH ranges.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would combine these references to solve the well-known design need for creating a storage-stable peptide formulation for therapeutic use. Because GLP-2 and glucagon are both members of the same peptide hormone superfamily and share over 50% amino acid sequence similarity, a POSITA would have been motivated to apply the successful stabilization techniques for glucagon taught by Kornfelt and Osterberg to the GLP-2 formulations disclosed in Drucker ’379.
    • Expectation of Success: A POSITA would have had a reasonable expectation of success. Kornfelt provided data showing that L-histidine and mannitol/sucrose created highly stable glucagon formulations that retained over 90% purity even after heat stress. The stabilizing properties of these common excipients were not specific to glucagon, and their known effectiveness across broad pH ranges would lead a POSITA to predictably achieve a stable GLP-2 formulation.

Ground 2: Obviousness of Kit Claims - Claims 61-67 are obvious over Drucker ’600 in view of Kornfelt, Osterberg, and Holthuis.

  • Prior Art Relied Upon: Drucker ’600 (WO 98/52600), Kornfelt (Patent 5,652,216), Osterberg (journal article), and Holthuis (Patent 5,496,801).

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground targeted the kit claims. Petitioner argued that Drucker ’600 disclosed a basic kit containing a lyophilized GLP-2 formulation in a sterile vial with a label providing instructions for use. The combination with Kornfelt and Osterberg supplied the claimed stabilizing agents (L-histidine) and bulking agents (mannitol/sucrose). Finally, Holthuis taught a medically useful kit that included a vial of sterile water for reconstitution and an injection device. Together, these references disclosed all elements of independent kit claim 61 and its dependent claims.
    • Motivation to Combine: The motivation was to create a complete, stable, and convenient-to-use therapeutic product, which is a standard objective in the pharmaceutical industry. A POSITA would logically combine the base GLP-2 kit from Drucker ’600 with the superior stabilization technology from Kornfelt/Osterberg and the standard, user-friendly components (sterile water, injection device) from Holthuis to create an improved and commercially viable product.
    • Expectation of Success: Success was highly predictable, as assembling kits containing a lyophilized drug, a separate diluent, and instructions for reconstitution was a routine and well-established practice in the pharmaceutical arts.

  • Additional Grounds: Petitioner asserted two additional grounds. Ground 3 argued claims 51 and 75 are obvious over the Ground 1 combination further in view of Munroe (a 1999 journal article), which was cited to explicitly teach that the claimed GLP-2 analog has GLP-2 receptor binding activity. Ground 4 similarly added Munroe to the Ground 2 combination to render kit claim 68 obvious for the same reason.

4. Key Claim Construction Positions

  • Petitioner argued that several key claim terms should be construed according to definitions provided by the patentee during prosecution to overcome indefiniteness rejections.
  • “analog”: Construed to mean a peptide incorporating one or more amino acid modifications into a natural GLP-2 peptide that retains biological activity. Petitioner relied on this broad definition to map prior art analogs onto the claims.
  • “an amount sufficient to stabilize the formulation”: Construed as an amount of histidine that "increases the length of time that the GLP-2 peptide remains intact," as defined in the ’886 patent specification. This allowed Petitioner to argue that the general stabilizing teachings of Kornfelt and Osterberg for glucagon met this specific functional limitation for GLP-2.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 46-52 and 61-75 of the ’886 patent as unpatentable.