PTAB

IPR2025-00176

Samsung Bioepis Co Ltd 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 aflibercept, a vascular endothelial growth factor (VEGF) antagonist. The claims are directed to formulations in vials or pre-filled syringes (PFS) with specific stability characteristics under storage conditions.

3. Grounds for Unpatentability

Ground 1: Obviousness over Fraser/Wulff - Vial Claims (Claims 1-12, 14-17, 19-20, 22-25, 51-53, 55 are obvious over Fraser, Wulff, and the 2006 Presentations, in view of the ’319 Publication and FDA Guidance)

  • Prior Art Relied Upon: Fraser (a 2004 journal article), Wulff (a 2002 journal article), 2006 Presentations (investor presentations by Patent Owner), the ’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 Fraser and Wulff disclosed the only known prior art formulation of aflibercept, an intravenous (IV) solution containing the same core excipients as the challenged claims: aflibercept, a phosphate buffer, polysorbate 20, and sucrose. The ’319 Publication disclosed aflibercept’s amino acid sequence and its expression in CHO cells, which implies glycosylation. The 2006 Presentations by the Patent Owner reported success using intravitreal aflibercept injections to treat wet age-related macular degeneration (AMD). FDA Guidance recommended using vials for injectable formulations.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA), motivated by the clinical success reported in the 2006 Presentations, would adapt the known IV formulation from Fraser/Wulff for safe intravitreal administration. Petitioner asserted this adaptation would involve obvious modifications: (1) reducing the injection volume from 2 mL to a standard 0.1 mL for intravitreal use; (2) adopting the 4 mg maximum tolerated dose from the presentations, yielding a 40 mg/mL concentration; and (3) significantly reducing the high 20% sucrose concentration to achieve an iso-osmotic solution safe for the eye.
    • Expectation of Success: A POSA would have a high expectation of success because aflibercept was proven safe for intravitreal injection, and the required modifications were described as routine adjustments to solve known problems of injection volume and osmolarity for ophthalmic formulations.
    • Key Aspects: Petitioner contended the claimed stability limitations (e.g., ≥98% native conformation after two months) are not separately patentable because they are inherent properties of the resulting obvious formulation. The petition argued that simply testing an obvious formulation and discovering its inherent stability does not render the formulation non-obvious.

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

  • Prior Art Relied Upon: Fraser, Wulff, 2006 Presentations, the ’319 Publication, and Nayar (a 2002 book chapter on protein formulation).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground is substantially similar to Ground 1 but challenges claims directed to storing the formulation in a pre-filled syringe (PFS) instead of a vial. The core arguments regarding the necessary modifications to the Fraser/Wulff formulation remain the same.
    • Motivation to Combine: The motivation to use a PFS stemmed from its well-known advantages. Petitioner cited Nayar, which taught that a PFS was the "most preferred" dosage form for a refrigerated therapeutic protein product because it offered convenience by eliminating the step of withdrawing the drug from a vial. A POSA would have found it obvious to use a PFS, a known and commercially desirable alternative to a vial for intravitreal administration.
    • Expectation of Success: As with Ground 1, a POSA would expect success in packaging the modified, stable aflibercept formulation in a standard PFS container, as it was a common and reliable delivery system for such therapeutics.

4. Key Claim Construction Positions

  • Petitioner argued that the term "about" in claim limitations such as "a pH of 'about 6.2-6.3'" should be interpreted to encompass values outside the literal range, accounting for measurement error inherent in pH meters at the time of the invention (+/- 0.1-0.2 pH units).
  • Based on this construction, Petitioner asserted that the pH of 6.0 disclosed in Fraser falls within the scope of "about 6.2," thereby satisfying this limitation of dependent claims.

5. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under 35 U.S.C. §325(d) is unwarranted because the core prior art references and obviousness combinations were not substantively considered during prosecution. The examiner's rejections were limited to obviousness-type double patenting and did not address the prior art combinations presented in the petition.
  • Petitioner also argued against discretionary denial under Fintiv (35 U.S.C. §314(a)), asserting that the parallel district court case involves over 50 patents. This makes it highly unlikely that the 48 challenged claims will be substantively litigated to a final verdict before the IPR concludes, especially since a trial schedule has not been set.

6. 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 Patent 11,084,865 as unpatentable.