PTAB

IPR2025-00233

Formycon AG v. Regeneron Pharmaceuticals Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: VEGF Antagonist Formulations Suitable for Intravitreal Administration
  • Brief Description: The ’865 patent discloses stable ophthalmic formulations of the anti-VEGF fusion protein aflibercept, comprising an organic co-solvent, a buffer, and a stabilizing agent, suitable for administration into the eye. The claims are directed to specific formulations stored in either a vial or a pre-filled syringe (PFS) that exhibit defined stability characteristics over time.

3. Grounds for Unpatentability

Ground 1: Claims 1-12, 14-17, 19-20, 22-25, 51-53, and 55 ("Vial Claims") are obvious over Fraser, Wulff, and the 2006 Presentations, in light of the '319 Publication and the FDA Container Closure Guidance.

  • Prior Art Relied Upon: Fraser (a 2004 journal article), Wulff (a 2002 journal article), 2006 Presentations (three Regeneron presentations from Feb/Mar 2006), '319 Publication (WO 00/75319), and FDA Container Closure Guidance (a 1999 FDA guidance document).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the only publicly known aflibercept formulation at the time was an intravenous formulation disclosed in Fraser and Wulff, which contained the same core excipients as the claimed invention: aflibercept, a phosphate buffer, polysorbate 20 (co-solvent), and sucrose (stabilizer). The 2006 Presentations disclosed the successful use of intravitreal aflibercept injections at doses up to 4 mg to treat wet age-related macular degeneration (AMD). Petitioner asserted that modifying the known Fraser/Wulff intravenous formulation for the demonstrated intravitreal use was obvious. This modification involved three routine steps: (1) selecting the 4 mg dose from the 2006 Presentations; (2) reducing the injection volume from 2 mL (in Fraser/Wulff) to the standard, safe 0.1 mL for intravitreal use, resulting in the claimed 40 mg/mL concentration; and (3) reducing the sucrose concentration from 20% to approximately 10% or less to make the formulation iso-osmotic and safe for the eye. The resulting formulation meets the limitations of the independent claims. Petitioner further contended that the claimed stability (e.g., ≥98% native conformation after two months) was an inherent property of this obvious formulation, not an inventive feature.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA), aware from the 2006 Presentations that intravitreal aflibercept was safe and effective for treating wet AMD, would be motivated to develop a suitable formulation for that purpose. The natural starting point would be the only known aflibercept formulation, that of Fraser and Wulff, which would then be adapted for intravitreal use through predictable and well-understood modifications to ensure proper dosage, volume, and ocular safety (iso-osmolarity).
    • Expectation of Success: A POSA would have a high expectation of success. The active ingredient, aflibercept, was already shown to be safe and effective when injected intravitreally in the 2006 Presentations. The required modifications—adjusting concentration, volume, and osmolarity—involved routine formulation techniques using common excipients known to be safe for intravitreal use.

Ground 2: Claims 26-36, 39-42, 44-45, 47-50, and 54 ("PFS Claims") are obvious over Fraser, Wulff, and the 2006 Presentations, in light of the '319 Publication and Nayar.

  • Prior Art Relied Upon: Fraser (a 2004 journal article), Wulff (a 2002 journal article), 2006 Presentations (three Regeneron presentations from Feb/Mar 2006), '319 Publication (WO 00/75319), and Nayar (a 2002 book chapter).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground is identical to Ground 1, addressing claims that recite the same formulation stored in a pre-filled syringe (PFS) instead of a vial. Petitioner argued that once the formulation itself was arrived at through the obvious modifications described in Ground 1, selecting a container was a simple design choice.
    • Motivation to Combine: The motivation to create the intravitreal formulation is the same as in Ground 1. For the container, Nayar taught that a PFS was the "most preferred" dosage form for therapeutic protein products because it offered convenience by eliminating the need to withdraw the drug from a vial. Given that vials and PFSs were the two common presentations for intravitreal drugs at the time, choosing a PFS for its known advantages would have been an obvious alternative to a vial.
    • Expectation of Success: A POSA would have expected success in packaging the obvious-to-make formulation in a standard PFS, as this was a conventional and well-understood method for administering injectable therapeutics.

4. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial would be unwarranted. Under 35 U.S.C. §325(d), Petitioner contended the art and arguments were not previously considered, as the Examiner only issued obviousness-type double patenting rejections during prosecution and did not substantively evaluate the obviousness combinations asserted in the petition. Under 35 U.S.C. §314(a), Petitioner argued against denial based on Fintiv by stipulating it would not pursue the same grounds in parallel district court litigation. Petitioner also argued that General Plastic/Valve concerns about serial petitions do not apply, as a separate IPR filed by another entity (Samsung Bioepis) does not create a "significant relationship" that would justify denial.

5. Relief Requested

  • Petitioner requested the institution of an inter partes review and cancellation of claims 1-12, 14-17, 19-20, 22-36, 39-42, 44-45, and 47-55 of the ’865 patent as unpatentable.