After the Federal Circuit’s January decisions¹ affirming the preliminary injunction orders that bar Samsung Bioepis (SB) and Formycon from launching their biosimilars to Regeneron’s eye injection product Eylea^® (see here for background and analysis on those decisions), it just affirmed two more district court decisions in biosimilars litigations relating to Eylea^®: one granting a preliminary injunction against Celltrion, and another denying a preliminary injunction against Amgen.²

Celltrion

The issues in the Celltrion appeal substantially overlapped with the SB and Formycon appeals, and Celltrion conceded during oral argument that the personal jurisdiction issue and the nexus issue are controlled by the SB Opinion. The only remaining issue on appeal concerned the obvious-type double-patenting (ODP) and specifically focused on the stability limitation. 

The asserted claims of the ’865 Patent recite “at least 98% of the VEGF antagonist is present in native conformation following storage at 5°C for two months as measured by size exclusion chromatography,” while claim 5 of the ’594 Patent (an alleged ODP reference³) recites that the VEGF trap be “stable for at least four months.”⁴

Celltrion raised two claim construction arguments regarding the stability limitation. First, it challenged the district court’s refusal to construe “stable” to require “the VEGF trap protein to be in at least 98% native conformation as measured by size-exclusion chromatography (SEC) after two-month storage at 5°C,” which is essentially recited in the asserted claims of the ’865 Patent. 

The district court rejected that argument because “the specification of the ’594 Patent has numerous descriptions of stability beyond simply 98% native conformation as measured by SEC.”⁵ For example, the ’594 Patent describes multiple aspects of stability and multiple ways to measure stability.⁶ It also discloses that levels of non-aggregation below 98% are desirable.⁷ The Federal Circuit agreed with the district court based on the record.⁸

Celltrion next argued that the district court’s conclusion that the 98% native conformation limitation is not inherent in claim 5 of the ’594 Patent was based on an incorrect implicit claim construction. Specifically, Celltrion argued that the asserted claims “require only that the formulation be sufficiently stable so that no more than 2% of whatever un-aggregated VEGF antagonist is present prior to storage aggregate[s] during the claimed storage period.”⁹ Celltrion argued that this limitation “defines a rate of aggregation over a particular time, under particular conditions.”¹⁰

The Federal Circuit found this argument “contradicts the plain claim language, which states that ‘at least 98% of the VEGF antagonist is present in native conformation following storage . . . for two months’ as measured by SEC.”¹¹ Indeed, “[n]othing in the claims or specification suggests that a ‘rate’ must be calculated.”¹²

Celltrion also challenged the district court’s finding that the stability limitation would not have been obvious. The Federal Circuit found that the record supports the district court’s finding that a POSA “beginning with claim 5 of the ‘594 patent would not have been motivated to achieve the 98% native conformation limitation and would not have had a reasonable expectation of achieving that level of native conformation after two-months’ storage.”¹³

In sum, Celltrion did not raise any new arguments that could convince the Federal Circuit to reverse the district court’s decision. 

Amgen

Regeneron’s appeal in the Amgen case presented a different issue from all other appeals: whether Regeneron established a likelihood of success in showing that Amgen’s biosimilar infringed the ’865 Patent.

The asserted claims all recite a formulation that comprises “a [VEGF] antagonist” and “a buffer.”¹⁴ Amgen’s formulation, unlike the other biosimilar versions of Eylea^® that contain a separate buffer, does not contain a separate buffer. The district court denied Regeneron’s motion for a preliminary injunction because the asserted claims require that the claimed “VEGF antagonist” be a separate component from the claimed “buffer” and therefore Regeneron failed to demonstrate a likelihood of success on the merits with respect to infringement.¹⁵

On appeal, Regeneron argued that the claimed “VEGF antagonist” can satisfy the claimed “buffer” and relied on extrinsic evidence to show that aflibercept, the VEGF antagonist in the formulation, was known in the art to function as a buffer. Regeneron also argued that the district court in Formycon construed the term “buffer” as “a substance that resists changes to pH . . . including, for example, histidine, phosphate and proteins like aflibercept.”¹⁶

The Federal Circuit disagreed. First, the court in Becton, Dickinson & Co. v. Tyco Healthcare Group, LP¹⁷ held that “[w]here a claim lists elements separately, the clear implication of the claim language is that those elements are distinct component[s] of the patented invention.”¹⁸ The asserted claims plainly recite a formulation comprising four separately listed components, including a “VEGF antagonist” and a “buffer.”¹⁹ Thus, the plain language “establishes a ‘clear implication’ that the VEGF antagonist and buffer components are distinct components of the claimed formulation.”²⁰

Regeneron argued that Becton did not apply because the district court previously construed the term “buffer” to include “proteins like aflibercept” in the Formycon Decision. The Federal Circuit rejected that argument because the district court properly applied the claim construction principles and was not bound by a preliminary construction in a different case dealing with different issues. 

Next, the Federal Circuit determined whether there is any evidence to overcome the implication of separateness under Becton, i.e., evidence showing “that the impliedly distinct components . . . can be satisfied by a single component.”²¹ The district court found that the record failed to overcome the implication of separateness and the Federal Circuit agreed. Specifically, the claims list the two limitations with “different concentrations and different units of measurement.”²² In addition, the “specification does not suggest that the VEGF antagonist can be a buffer or vice versa” and instead “describes a formulation containing a VEGF antagonist plus a distinct buffer component.”²³

Regeneron argued that proteins like aflibercept were known buffers, as the district court in Formycon found, and thus the patent did not need to list what is known.²⁴ The Federal Circuit again rejected that argument because the preliminary construction in Formycon was not binding and “nothing in the specification indicates that the VEGF antagonist ‘might’ also satisfy the distinct ‘buffer’ component.”²⁵ In addition, even though the term “buffer” was not defined in the specification, it does not mean that “the term is divorced from what is so clearly implied by the claims and the specification alike.”²⁶

Finally, Regeneron argued that the district court improperly disregarded the extrinsic evidence teaching that proteins were known buffers. The Federal Circuit rejected that argument for two reasons. First, “the district court did not need to consider the extrinsic evidence given the overwhelming evidence in the intrinsic record.”²⁷ Second, the district court nevertheless considered extrinsic evidence and correctly found that the extrinsic evidence also supported the separateness of the “VEGF antagonist” and the “buffer” limitations.

What’s Next

Amgen launched its biosimilar in November 2024, shortly after the district court’s denial of Regeneron’s motion for preliminary injunction. The Federal Circuit’s affirmance of the district court’s denial, however, does not end the patent fight between Regeneron and Amgen regarding the Eylea^® biosimilar. Regeneron has asserted 31 other patents in the district court, which were not part of the preliminary injunction and continue to pose infringement risk for Amgen.

The Federal Circuit heard the oral argument in Mylan’s appeal concerning the grant of a permanent injunction with respect to its Eylea® biosimilar, and is expected to issue its decision in the near future.

The Sandoz case is still at the pleading stage in the district court. In its answer, Sandoz asserted inequitable conduct defenses and counterclaims against three out of the 46 asserted patents. Regeneron moved to strike the affirmative defenses and dismiss the counterclaims concerning two patents.  That motion is currently pending.

Below is an updated chart for each Eylea^® biosimilar application and status of the respective cases.

1 Regeneron Pharms., Inc. v. Mylan Pharms. Inc., 127 F.4th 896 (Fed. Cir. 2025) (“SB Opinion”); Regeneron Pharms., Inc. v. Mylan Pharms. Inc., Nos. 2024-2009, 2024-2019, 2024-2156, 2025 U.S. App. LEXIS 1976 (Fed. Cir. Jan. 29, 2025).

2 Regeneron Pharms., Inc. v. Mylan Pharms. Inc., Nos. 2024-2058, 2024-2147, 2025 U.S. App. LEXIS 5102 (Fed. Cir. Mar. 5, 2025) (“Celltrion Opinion”); Regeneron Pharms., Inc. v. Mylan Pharms. Inc., No. 2024-2351, 2025 U.S. App. LEXIS 5990 (Fed. Cir. Mar. 14, 2025) (“Amgen Opinion”).

3 Although the parties disputed whether the ’594 Patent qualifies as a proper ODP reference, the Federal Circuit did not reach that because it affirmed the district court’s decision that Celltrion has not established that the claim difference concerning the stability requirement is not patentably distinct. 

4 Celltrion Opinion, at 6.

5 Id. at 7. 

6 Id.

7 Id.

8 Id.

9 Id. at 8 (quoting Appellant’s Br.)

10 Id.

11 Id. at 8.

12 Id.

13 Id. at 9.

14 Amgen Opinion, at 4-5.

15 Id. at 8.

16 In re Aflibercept Pat. Litig., No. 1:23-cv-97, 2024 WL 3423047, at *15–17 (N.D. W. Va. July 9, 2024).

17 616 F.3d 1249 (Fed. Cir. 2010).

18 Id. at 1254 (internal quotation marks omitted).

19 Amgen Opinion, at 9.

20 Id. at 9-10.

21 Id. at 12.

22 Id. at 13.

23 Id. at 14.

24 Id. at 15.

25 Id. at 15-16.

26 Id. at 17.

27 Id. at 18.