Fresenius Kabi SwissBioSim GmbH et al.

Prosecution History analysis

Examiner Search analysis

Invalidity Framework analysis

Petition

Petition Analysis

## 1. Case Identification
- Case #: [IPR2025-01268](https://ai-lab.exparte.com/case/ptab/IPR2025-01268)
- Patent #: 11,084,865
- 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.
- Challenged Claims: 1-5, 7-30, and 32-50

## 2. Patent Overview
- Title: VEGF Antagonist Formulations Suitable for Intravitreal Administration
- Brief Description: The [’865 patent](https://ai-lab.exparte.com/case/ptab/IPR2025-01268/doc/1001) describes stable ophthalmic formulations of a vascular endothelial growth factor (VEGF) antagonist, specifically the fusion protein aflibercept. The formulations are intended for intravitreal administration to treat ocular diseases such as wet age-related macular degeneration (AMD) and are characterized by specific excipients and stability profiles.

## 3. Grounds for Unpatentability

#### Ground 1: Anticipation over Dix - Claims 1-5, 7-30, and 32-50 are anticipated by Dix under 35 U.S.C. §102.
  - **Prior Art Relied Upon:** Dix (Patent 10,406,226).
  - **Core Argument for this Ground:**
    - **Prior Art Mapping:** Petitioner argued that Dix, which qualifies as prior art under pre-AIA §102(e)(2), disclosed all elements of the challenged claims. Independent claims 1 and 26 require a vial or pre-filled syringe containing an ophthalmic formulation with a specific VEGF antagonist, an organic co-solvent, a buffer, and a stabilizing agent. Petitioner asserted that Dix expressly disclosed formulations of the same VEGF antagonist (aflibercept, identified as SEQ ID NO:4), stored in vials or pre-filled syringes, and containing the same classes of excipients, including specific examples of polysorbate 20 (co-solvent), phosphate buffer, and sucrose (stabilizer).

    - For dependent claims, Petitioner mapped specific concentrations and parameters to Dix's disclosures. The challenged 40 mg/ml aflibercept concentration (claims 2, 27) was argued to be anticipated by Dix's disclosed range of 10-50 mg/ml. The petition contended that Patent Owner failed to demonstrate any "criticality" for the 40 mg/ml point within Dix's range, making the specific value an unpatentable selection. Similarly, claimed ranges for polysorbate 20 (e.g., 0.03-0.1%), buffer concentration (5-25 mM), pH (6.2-6.3), and sucrose (1-10%) were all shown to be disclosed by or overlap with ranges explicitly taught in Dix.

    - **Key Aspects:** The core of the anticipation argument rested on two principles: inherency and lack of criticality. Petitioner contended that the claimed stability limitations (e.g., "at least 98% of the VEGF antagonist is present in native conformation" after storage) were not novel features but were inherent properties of the formulations already disclosed in Dix. The petition pointed to stability data within Dix (measured by SE-HPLC, a type of SEC) showing that its disclosed formulations met or exceeded the claimed stability requirements. Petitioner further argued that the selection of a 40 mg/ml concentration from Dix's 10-50 mg/ml range was not patentable because no unexpected results or criticality were associated with that specific value.

## 4. Key Claim Construction Positions
- Petitioner argued that the preamble phrase "suitable for intravitreal administration" should not be treated as a claim limitation because it merely states an intended use. However, Petitioner contended that even if the phrase were limiting, the formulations disclosed in Dix would meet this limitation. Dix's formulations use the same well-known, biocompatible excipients as the [’865 patent](https://ai-lab.exparte.com/case/ptab/IPR2025-01268/doc/1001), which a person of ordinary skill in the art (POSA) would have recognized as suitable for injection into the eye without further testing.

## 5. Key Technical Contentions (Beyond Claim Construction)
- **Inherency of Stability:** The petition’s primary technical contention was that the claimed stability metrics (both native conformation percentage and turbidity levels) are inherent properties of the prior art formulation. Petitioner argued that since Dix disclosed the necessary components (aflibercept, buffer, co-solvent, stabilizer) at overlapping concentrations, the resulting stability is an inevitable, unpatentable consequence. The petition used stability data from both Dix and the [’865 patent](https://ai-lab.exparte.com/case/ptab/IPR2025-01268/doc/1001) itself to demonstrate that simply combining the disclosed ingredients necessarily achieves the claimed stability.
- **Lack of Criticality for Claimed Ranges:** A central contention was that the specific 40 mg/ml concentration of aflibercept recited in dependent claims is merely one point within a narrow range (10-50 mg/ml) disclosed by Dix. Citing case law such as *ClearValue*, Petitioner asserted that claiming a point within a prior art range only becomes patentable if the patentee can demonstrate that the specific point is "critical" and yields unexpected results not found elsewhere in the range. The petition argued that Patent Owner provided no evidence of such criticality for 40 mg/ml.

## 6. Arguments Regarding Discretionary Denial
- Petitioner argued that discretionary denial under §314(a) or §325(d) would be inappropriate. It distinguished this IPR from prior petitions against the [’865 patent](https://ai-lab.exparte.com/case/ptab/IPR2025-01268/doc/1001), which were denied on discretionary grounds, by noting that this is the first challenge based on Dix's anticipation of the claims. Petitioner asserted that this ground is substantially different from those previously considered by the Board. Furthermore, the petition heavily referenced a recent Federal Circuit oral argument in *Regeneron v. Mylan*, where the panel expressed significant skepticism about the patentability of the 40 mg/ml claim over Dix's disclosure. Petitioner argued that the court's pointed questions on criticality and the subsequent settlement of that case represent a significant new development that weighs strongly in favor of institution.

## 7. Relief Requested
- Petitioner requested institution of an inter partes review and cancellation of claims 1-5, 7-30, and 32-50 of the [’865 patent](https://ai-lab.exparte.com/case/ptab/IPR2025-01268/doc/1001) as unpatentable.

Regeneron's aflibercept formulation patent faces anticipation: Dix prior art cited against 45 claims, arguing lack of criticality for its 40 mg/ml dose.