PTAB

IPR2021-00816

Regeneron Pharmaceuticals Inc v. Novartis Pharma AG

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1. Case Identification

2. Patent Overview

  • Title: Terminally Sterilized Pre-Filled Syringe
  • Brief Description: The ’631 patent is directed to a terminally sterilized, pre-filled glass syringe for intravitreal injection. The syringe contains a VEGF-antagonist solution, has a specific barrel size (0.5-1 ml), a defined low amount of silicone oil (1-100 µg), and a low stopper break loose force (<11 N).

3. Grounds for Unpatentability

Ground 1: Obviousness over Sigg and Boulange - Claims 1-3, 5-9, 14-22, and 24 are obvious over Sigg in view of Boulange.

  • Prior Art Relied Upon: Sigg (WO 2011/006877) and Boulange (WO 2009/030976).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Sigg disclosed a terminally sterilized pre-filled syringe containing the VEGF-antagonist ranibizumab for intravitreal injection. However, Sigg did not specify the siliconization method. Boulange disclosed a pre-filled glass syringe using a "baked-on" siliconization method that results in low silicone oil amounts (40 µg for a 1 mL syringe) and low stopper forces (<11 N and <5 N), meeting the limitations of independent claim 1.
    • Motivation to Combine: A POSITA would combine Sigg's terminally sterilized drug-filled syringe with Boulange's low-silicone barrel to solve the well-known problems of silicone oil interacting with biologic drugs and the risk of injecting oil droplets into a patient's eye. Petitioner asserted that reducing silicone oil via baked-on siliconization was a known solution to a known problem.
    • Expectation of Success: A POSITA would have a high expectation of success because Boulange explicitly taught syringes with the claimed silicone oil levels and resulting forces. Furthermore, Sigg's vaporized hydrogen peroxide (VHP) sterilization method was described as broadly applicable and designed to prevent sterilizing gas from entering the syringe, meaning it would not interfere with the properties of Boulange's baked-on syringe barrel.

Ground 2: Obviousness over Lam and Boulange - Claims 1-3, 5-9, 14-22, and 24 are obvious over Lam in view of Boulange.

  • Prior Art Relied Upon: Lam (WO 2008/077155) and Boulange (WO 2009/030976).

  • Core Argument for this Ground:

    • Prior Art Mapping: Petitioner contended this ground was analogous to Ground 1. Lam disclosed the terminal sterilization of pre-filled glass syringes containing the VEGF-antagonist ranibizumab, but used ethylene oxide (EtO) instead of VHP. As in Ground 1, Boulange supplied the teaching of a baked-on, low-silicone syringe barrel with the claimed low break loose and slide forces.
    • Motivation to Combine: The motivation was identical to that in Ground 1: to improve Lam's sterilized syringe by incorporating Boulange's known low-silicone technology to enhance drug stability and patient safety.
    • Expectation of Success: The expectation of success was similarly high. Combining Lam's EtO sterilization process with Boulange's syringe was predictable, as both references were directed to standard pre-filled syringe technology, and a POSITA would expect the combination to work for its intended purpose.

  • Additional Grounds: Petitioner asserted additional obviousness challenges based on Sigg or Lam in view of Boulange, combined with: Fries (to teach the specific DC365 silicone oil emulsion of claim 4), Furfine (to teach the non-antibody VEGF-antagonist aflibercept of claims 11-13), the 2008 Macugen Label (to teach the method of priming the syringe of claim 25), and Dixon (to teach the method of treating a patient with a non-antibody after prior antibody treatment, as recited in claim 26).

4. Key Claim Construction Positions

  • "Terminally sterilized": Petitioner argued that, in the context of the ’631 patent, this term refers to a process where the outside of a filled and packaged syringe is sterilized (e.g., with sterilizing gas), while contact between the sterilizing agent and the drug product inside the syringe is minimized. This construction was central to arguing that prior art sterilization methods from Sigg and Lam were directly applicable to pre-filled syringes without affecting the internal components or drug product.

5. Arguments Regarding Discretionary Denial

  • Petitioner argued extensively that discretionary denial under §314(a) or §325(d) would be inappropriate. A prior IPR (IPR2020-01317) was denied under Fintiv based on a parallel ITC investigation that Patent Owner assured the Board would proceed to a final determination. However, Patent Owner terminated the ITC investigation just 12 days before the scheduled trial, after the ITC Staff had issued a brief concluding the challenged claims were invalid. Petitioner characterized this as "gamesmanship" intended to avoid a validity determination and argued that the Fintiv factors now strongly favor institution, as the parallel district court case is stayed with no trial date set. Petitioner also argued against denial under §325(d), asserting the prior art was not cumulative because neither Sigg nor Lam, which were not before the Examiner, disclosed terminally sterilizing a pre-filled syringe containing a VEGF-antagonist.

6. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-26 of the ’631 patent as unpatentable.