PTAB

IPR2021-00880

Mylan Pharmaceuticals Inc v. Regeneron Pharmaceuticals Inc

Log In
Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Use of a VEGF Antagonist to Treat Angiogenic Eye Disorders
  • Brief Description: The ’069 patent relates to methods for treating angiogenic eye disorders, such as age-related macular degeneration (AMD), by administering a VEGF antagonist known as aflibercept (VEGF Trap-Eye). The claimed method involves a sequential dosing regimen comprising a single initial dose, one or more secondary doses administered 2 to 4 weeks apart, and one or more subsequent tertiary doses administered on an as-needed, or pro re nata (PRN), basis.

3. Grounds for Unpatentability

Ground 1: Anticipation based on CLEAR-IT-2 Trial - Claims 1 and 9-12 are anticipated by Heier-2009 or Dixon.

  • Prior Art Relied Upon: Heier-2009 (a 2009 clinical update) and Dixon (a 2009 investigational drug review).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that both Heier-2009 and Dixon independently disclosed every element of the challenged claims by reporting the design and successful results of Regeneron’s Phase 2 "CLEAR-IT-2" clinical trial. This trial evaluated aflibercept for treating AMD using a regimen of initial monthly loading doses (an initial dose and subsequent secondary doses) followed by a PRN maintenance phase (tertiary doses). Heier-2009 specifically described treatment arms with three or more monthly 2.0 mg injections followed by as-needed dosing, which showed significant improvements in visual acuity. Dixon similarly described the CLEAR-IT-2 regimen of four monthly doses followed by PRN administration, meeting the claimed sequence of initial, secondary, and tertiary doses.
    • Key Aspects: The core of this ground was that Regeneron’s own widely-published clinical trial data, available years before the patent’s priority date, explicitly taught the claimed dosing method.

Ground 2: Invalidity based on VIEW1/VIEW2 Trial - Claims 1 and 8-12 are anticipated and/or obvious over Dixon.

  • Prior Art Relied Upon: Dixon (a 2009 publication).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted this ground based on arguments the Patent Owner made during prosecution of the ’069 patent. To overcome a rejection, the Patent Owner had relied on results from the "VIEW1/VIEW2" clinical trials, arguing that its every-eight-week dosing regimen was encompassed by the claims and produced unexpected results. Petitioner argued that the Dixon reference, published before the patent's priority date, expressly disclosed the design of these same VIEW1/VIEW2 trials. The disclosed regimen involved three initial monthly doses (an initial dose at week 0 and two secondary doses at weeks 4 and 8) followed by dosing every 8 weeks.
    • Motivation to Combine (for §103 obviousness aspect): Applying the Patent Owner's own interpretation of the claim scope, Petitioner contended that Dixon’s disclosure of the VIEW1/VIEW2 regimen anticipated the claims. Alternatively, it would have been obvious to a person of ordinary skill in the art (POSITA) to use the regimen described in Dixon for treating AMD, especially given Dixon's characterization of aflibercept as a "promising" drug and the well-documented market pressure to find less-frequent dosing schedules than the monthly standard.
    • Expectation of Success: A POSITA would have had a high expectation of success based on Dixon’s report of positive Phase 2 data and the launch of the large-scale Phase 3 VIEW1/VIEW2 trials.

Ground 3: Obviousness over Heier-2009 in view of Mitchell or Dixon - Claims 1 and 8-12 are obvious over Heier-2009 in combination with either Mitchell or Dixon.

  • Prior Art Relied Upon: Heier-2009, Mitchell (a 2009 publication on ranibizumab trials), and Dixon.

  • Core Argument for this Ground:

    • Prior Art Mapping: Petitioner argued that Heier-2009 taught that aflibercept was effective for AMD using a PRN dosing regimen following several monthly loading doses. Mitchell and Dixon both described the prevailing trend in anti-VEGF therapy, specifically for the competitor drug ranibizumab (Lucentis), was to use a "PrONTO-style" regimen of three initial monthly loading doses followed by PRN maintenance. This specific three-dose loading schedule was shown to be highly effective and became a clinical standard.
    • Motivation to Combine: A POSITA would combine the teachings of Heier-2009 with Mitchell or Dixon to optimize the aflibercept regimen. Knowing from Heier-2009 that a loading-dose-plus-PRN strategy worked for aflibercept, the skilled artisan would have been motivated to adopt the specific, well-established three-dose loading regimen from the ranibizumab art (disclosed in Mitchell and Dixon) to reduce the treatment burden while maintaining efficacy. The motivation was driven by the known "time and financial burden" of monthly injections.
    • Expectation of Success: A POSITA would have reasonably expected success because clinical trials had already shown that aflibercept and ranibizumab, despite molecular differences, had comparable efficacy in treating AMD. The successful outcomes of the PrONTO regimen for ranibizumab would have created a strong expectation that a similar dosing structure would be successful for aflibercept.

  • Additional Grounds: Petitioner asserted an additional anticipation challenge based on a 2009 Regeneron press release disclosing a six-month loading dose regimen followed by PRN dosing for treating Central Retinal Vein Occlusion (CRVO).

4. Key Claim Construction Positions

  • “Initial Dose,” “Secondary Dose,” and “Tertiary Dose”: Petitioner argued that these terms should be given their plain and ordinary meaning as explicitly defined in the ’069 patent’s specification, which defines them based purely on their temporal sequence of administration. Petitioner contended that "initial dose" means the first dose, "secondary doses" are those after the initial dose, and "tertiary doses" are those after the secondary doses. This construction was central to mapping the prior art regimens, which followed this sequence.
  • Rejection of Functional Limitations: Petitioner argued against the Patent Owner’s anticipated attempt to import functional limitations into the claim terms, particularly for "tertiary dose." Petitioner asserted that construing "tertiary dose" to require "maintain[ing] a therapeutic effect" would improperly read a limitation from a specific embodiment into the claims, contradicting the patent’s broader, express definition.
  • “Method for treating”: Petitioner contended that the preamble phrase "method for treating" is a non-limiting statement of intended use and does not impose a specific, measurable efficacy requirement on the claimed method steps.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1 and 8-12 of the ’069 patent as unpatentable.