Fresenius Kabi SwissBiosim, GmbH et al.

Prosecution History analysis

Examiner Search analysis

Invalidity Framework analysis

Petition

Petition Analysis

## 1. Case Identification
- Case #: [IPR2025-01269](https://ai-lab.exparte.com/case/ptab/IPR2025-01269)
- Patent #: [10,828,345](https://ai-lab.exparte.com/patent/10828345)
- Filed: July 14, 2025
- Petitioner(s): [Fresenius Kabi SwissBioSim GmbH](https://ai-lab.exparte.com/party/fresenius--kabi-usa-llc)
- Patent Owner(s): [Regeneron Pharmaceuticals, Inc.](https://ai-lab.exparte.com/party/regeneron-pharmaceuticals-inc)
- Challenged Claims: 1-11

## 2. Patent Overview
- Title: Use of a VEGF Antagonist to Treat Angiogenic Eye Disorders
- Brief Description: The [’345 patent](https://ai-lab.exparte.com/case/ptab/IPR2025-01269/doc/1001) discloses methods for treating angiogenic eye disorders by sequentially administering a VEGF antagonist, specifically aflibercept (VEGF Trap-Eye). The claimed method comprises an initial dose, followed by one or more secondary doses administered four weeks after the preceding dose, and subsequently one or more tertiary doses administered 12 weeks after the immediately preceding dose.

## 3. Grounds for Unpatentability

#### Ground 1: Anticipation of Claims 1-9 by Clinical Trial Disclosures
- **Prior Art Relied Upon:** [Dixon](https://ai-lab.exparte.com/case/ptab/IPR2025-01269/doc/1007) (a 2009 article in *Expert Opinion on Investigation Drugs*), [NCT-377](https://ai-lab.exparte.com/case/ptab/IPR2025-01269/doc/1018) (a ClinicalTrials.gov record), [NCT-795](https://ai-lab.exparte.com/case/ptab/IPR2025-01269/doc/1017) (a ClinicalTrials.gov record), and [Regeneron (8-May-2008)](https://ai-lab.exparte.com/case/ptab/IPR2025-01269/doc/1022) (a press release).
- **Core Argument for this Ground:**
    - **Prior Art Mapping:** Petitioner argued that claims 1-9 are anticipated under 35 U.S.C. §102 because each of the four cited references independently discloses every element of the claimed method. The references describe the design of the VIEW 1 and VIEW 2 Phase III clinical trials for treating age-related macular degeneration (AMD) with aflibercept. Petitioner asserted these trials taught the claimed dosing regimen: an initial dose, followed by monthly doses for the first year (meeting the "secondary doses" administered four weeks apart), and a subsequent flexible, pro re nata (p.r.n.) phase where doses could be administered as infrequently as every 12 weeks (meeting the "tertiary doses" limitation).
    - **Key Aspects:** Petitioner contended that the Dixon article explicitly cites and incorporates the NCT-377 clinical trial record by reference, directly linking the article’s summary of the dosing protocol to the specific trial details that disclose the 12-week tertiary dosing interval.

#### Ground 2: Obviousness of Claims 1-9 over Dixon and NCT-377
- **Prior Art Relied Upon:** Dixon (a 2009 article in *Expert Opinion on Investigation Drugs*) and NCT-377 (a ClinicalTrials.gov record).
- **Core Argument for this Ground:**
    - **Prior Art Mapping:** As an alternative to anticipation, Petitioner argued claims 1-9 are obvious over Dixon in view of NCT-377. Dixon teaches treating AMD with aflibercept using initial monthly loading doses followed by a flexible p.r.n. dosing schedule. NCT-377 provides the specific protocol for the VIEW 2 trial cited in Dixon, explicitly disclosing that the p.r.n. dosing could occur "no less frequently than every 12 weeks."
    - **Motivation to Combine:** A person of ordinary skill in the art (POSITA) would combine the teachings because Dixon explicitly cites the VIEW 2 trial (NCT-377) and directs the reader to it for details on the study design. A POSITA would naturally consult the cited reference for a more complete understanding of the dosing regimen.
    - **Expectation of Success:** The combination carried a high expectation of success as it involved merely looking up the specific details of a clinical trial protocol that was expressly referenced in the primary publication.

#### Ground 3: Obviousness of Claims 10-11 (Diabetic Retinopathy/DME)
- **Prior Art Relied Upon:** Any one of Dixon, NCT-377, NCT-795, or Regeneron (8-May-2008), in combination with [Regeneron (18-Feb-2010)](https://ai-lab.exparte.com/case/ptab/IPR2025-01269/doc/1052) (a press release announcing positive Phase 2 results for DME).
- **Core Argument for this Ground:**
    - **Prior Art Mapping:** Claims 10 and 11 apply the dosing regimen of the preceding claims to the treatment of diabetic retinopathy (DR) and diabetic macular edema (DME), respectively. The primary references (Dixon, etc.) establish the claimed dosing regimen for AMD. The Regeneron (18-Feb-2010) press release disclosed that aflibercept showed positive results in a Phase 2 study for treating DME.
    - **Motivation to Combine:** A POSITA would have been motivated to apply the known aflibercept dosing regimen for AMD to treat DR and DME. The motivation stemmed from several factors: (1) the known shared pathogenesis of AMD and DR/DME, which are both driven by VEGF-mediated angiogenesis; (2) the established desire in the art for less-frequent dosing schedules for DR/DME to reduce treatment burden; and (3) the positive Phase 2 data in the Regeneron (18-Feb-2010) reference confirming aflibercept's efficacy in DME.
    - **Expectation of Success:** The positive clinical data for aflibercept in DME, combined with the known biological mechanism and the recognized benefits of a less-frequent injection schedule, would have provided a POSITA with a strong and reasonable expectation of success.

## 4. Key Claim Construction Positions
- **"treating":** Petitioner argued for the term's plain and ordinary meaning, defined as "administering a therapeutic to a patient, without a specific degree of efficacy required." This construction was adopted by the PTAB in a related case and opposes any importation of a heightened efficacy standard into the claim.
- **"initial dose," "secondary dose," "tertiary dose":** Petitioner argued these terms are expressly defined in the ’345 patent’s specification based on their temporal sequence. The "initial dose" is the first dose, "secondary doses" are those after the initial dose, and "tertiary doses" are those after the secondary doses.

## 5. Key Technical Contentions (Beyond Claim Construction)
- A foundational technical argument asserted by Petitioner was that the terms "aflibercept" and "VEGF Trap-Eye" were used synonymously and interchangeably in the prior art to refer to the same molecule. Petitioner provided evidence from scientific publications and the Patent Owner's own statements in related proceedings to argue that a POSITA would have understood these terms to refer to the identical active ingredient, thus allowing the teachings from various references to be combined and applied to the claimed invention.

## 6. Relief Requested
- Petitioner requested the institution of an inter partes review and the cancellation of claims 1-11 of Patent 10,828,345 as unpatentable.

Regeneron's aflibercept patent challenged: clinical trial art cited for anticipation & obviousness against all 11 claims on a 12-week dosing schedule.