PTAB

PGR2025-00085

Alvotech HF v. Regeneron Pharmaceuticals Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Methods for Treating Angiogenic Eye Disorders with High Doses of VEGF Receptor Fusion Proteins
  • Brief Description: The ’036 patent relates to methods of treating angiogenic eye disorders by administering a high-concentration (≥100 mg/ml), high-dose (≥8 mg) aqueous pharmaceutical formulation of a VEGF receptor fusion protein, such as aflibercept, in a low volume (≤100 microliters) with a specific viscosity (about 5-15 cP).

3. Grounds for Unpatentability

Ground 1: Obviousness over Vitti, AU EYLEA Label, and Larson - Claims 1 and 4-38 are obvious over Vitti, AU EYLEA Label, and Larson.

  • Prior Art Relied Upon: Vitti (Application # 2016/0144025), AU EYLEA Label (a 2017 product information document), and Larson (Application # 2015/0071920).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Vitti, a Regeneron application, disclosed aflibercept formulations with concentrations up to 115 mg/mL and doses up to 10 mg in volumes up to 100 µL, meeting the patent’s concentration, dose, and volume limitations. The AU EYLEA Label allegedly confirmed the safety of the claimed dose range by teaching that an 8 mg "overdose" of aflibercept was "generally well tolerated" in clinical trials. Larson was cited for teaching that the desirable viscosity for high-concentration protein formulations administered via small-gauge needles (like the 30-gauge needle taught in the Label) is preferably "less than or about 10 cP," which overlaps and renders obvious the claimed 5-15 cP range.
    • Motivation to Combine: A POSITA would combine these references to reduce the frequency of intravitreal injections and lessen the associated patient burden, a well-known goal in the art. Vitti and the Label provided the high-concentration and high-dose parameters for aflibercept, while Larson supplied the known target viscosity necessary to ensure injectability for such a formulation.
    • Expectation of Success: Petitioner asserted a POSITA would have an expectation of success because Vitti taught stable, high-concentration aflibercept formulations were achievable, the Label showed high doses were safe, and Larson confirmed that formulating to achieve the target viscosity was a known practice.

Ground 2: Obviousness over Furfine, Dix, Label, Fiedler, and Larson - Claims 1 and 4-38 are obvious over Furfine, Dix, AU EYLEA Label, and Fiedler in view of Larson.

  • Prior Art Relied Upon: Furfine (Patent 7,608,261), Dix (Patent 8,921,316), AU EYLEA Label, Fiedler (Application # 2017/0232199), and Larson.
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground presented an alternative combination where earlier Regeneron patents, Furfine and Dix, disclosed stable aflibercept formulations with concentrations up to and including 100 mg/mL that were suitable for intravitreal injection. Fiedler was cited for teaching that conventional injection volumes for such ophthalmic drugs were between 30 to 100 µL. The AU EYLEA Label again provided evidence that an 8 mg dose was well-tolerated. Larson was used to supply the target viscosity range for high-concentration formulations intended for injection.
    • Motivation to Combine: The motivation was identical to Ground 1: creating a high-dose formulation to reduce treatment frequency. Petitioner argued a POSITA would logically look to Regeneron's foundational patents (Furfine, Dix) for formulation guidance, Fiedler for standard injection volumes, the Label for dose safety data, and Larson for viscosity targets.
    • Expectation of Success: Petitioner contended success was expected because Furfine and Dix explicitly taught stable 100 mg/mL aflibercept formulations suitable for eye injections. A POSITA would reasonably expect to successfully administer a known-safe dose (8 mg from the Label) in a conventional volume (from Fiedler) at a known desirable viscosity (from Larson) through routine optimization.

Ground 3: Lack of Written Description - Claims 1-38 are unpatentable under 35 U.S.C. §112(a).

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground is based on the ’036 patent's own specification.
    • Core Argument: Petitioner argued the ’036 patent’s specification failed to demonstrate that the inventors possessed the full scope of the claimed invention. The claims recite a broad genus of formulations defined by functional requirements (e.g., a viscosity of 5-15 cP) but only disclose a narrow set of examples. Critically, Petitioner contended that every formulation in the specification for which viscosity data is provided contains a buffer, and the specification demonstrates that the type of buffer (e.g., histidine vs. phosphate) has a significant impact on achieving the required viscosity. However, the claims do not require a buffer. Petitioner argued that because the specification provides no examples of achieving the claimed viscosity without a buffer and never suggests a buffer is optional, the inventors did not demonstrate possession of the full, broad scope of the claims, rendering them invalid for lack of written description.

  • Additional Grounds: Petitioner asserted additional obviousness challenges against claims 2 and 3 based on the combinations from Ground 1 and Ground 2, with the further addition of the 2011 EYLEA Clinical Review. This reference was used to teach that intravitreal aflibercept did not cause a significant increase in blood pressure, which maps to a specific limitation recited in dependent claims 2 and 3.

4. Relief Requested

  • Petitioner requests institution of Post Grant Review and cancellation of claims 1-38 of the ’036 patent as unpatentable.