Note: This post addresses a Federal Circuit decision that issued on March 14, 2025. This appeal involved Plaintiff-Appellant Regeneron Pharmaceuticals, Inc., Defendant-Appellee Amgen Inc. (Case 24-2351). At trial, this case also included Defendants Mylan Pharmaceuticals Inc.; Amgen USA, Inc.; Biocon Biologics Inc.; Celltrion, Inc.; Formycon AG; and Samsung Bioepsis Co.; as well as the Defendants-Appellee.
By Kevin E. Noonan --
The Defendants in biosimilar litigation involving Regeneron's EYLEA biologic drug got off the schneid last week (see "Regeneron Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc. (Fed. Cir. 2025)," involving Defendant-Appellant Celltrion), when one of the Defendants (Amgen) obtained a decision affirming the District Court's denial of a preliminary injunction under the litigation provisions of the BPCIA.
As in the earlier appeals, Regeneron's injunction motion was based on infringement of U.S. Patent No. 11,084,865 by Amgen's EYLEA biosimilar (designated ABP 938) and the appeal was limited to the propriety of the District Court's denial thereof to Regeneron. The basis for the District Court's denial was that Regeneron had not satisfied the burden for being granted a PI, that they were likely to succeed on the merits, and this determination was based on differences between Regeneron's approved formulation and Amgen's biosimilar version of it.
Regeneron's '865 patent recited in representative claim 1 the components of its formulation of its EYLEA biologic drug (aflibercept):
1. A vial comprising an ophthalmic formulation suitable for intravitreal administration that comprises:
a vascular endothelial growth factor (VEGF) antagonist,
an organic co-solvent,
a buffer,
and a stabilizing agent,
wherein said VEGF antagonist fusion protein is glycosylated and comprises amino acids 27-457 of SEQ ID NO:4; and
wherein 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.
(wherein the italicized limitations were important to the district court's denial of the PI).
The specific ingredients that differed in Amgen's formulation and Regeneron's patented formulation was the absence of the buffer recited in the '865 patent claims. As produced by Amgen, the opinion explains that "Amgen had discovered a way to prepare and formulate the active ingredient, aflibercept, in a manner that eliminates the need for a separate buffer component—i.e., the aflibercept itself provides sufficient buffering capacity to stabilize the formulation."
The District Court construed the '865 patent claims to require that the aflibercept and buffer were separate components ("[w]here a claim lists elements separately, the clear implication of the claim language is that those elements are distinct components of the patented invention" (emphasis in the opinion)), relying on Becton, Dickinson & Co. v. Tyco Healthcare Grp., LP, 616 F.3d 1249, 1255 (Fed. Cir. 2010), for the principle that "[t]here can be no literal infringement where a claim requires two separate structures and one such structure is missing from an accused [product]." But this is just a presumption, and the District Court then considered whether there was a basis to overcome the "clear implication" it applied in its initial claim construction (it did not). In coming to this conclusion, the District Court assessed both intrinsic and extrinsic evidence, which the opinion asserts "only reinforced the implication that the 'VEGF antagonist' and 'buffer' must be separate components of the claimed formulation." The Court was careful to note that while the term "buffer" had been construed in earlier litigation with co-defendant Formycon (see "Regeneron Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc. (Fed. Cir. 2025)"), the issue on claim construction before the District Court here was different to the extent that the issues raised by Amgen in this litigation were different (if only because the Court was tasked to determine whether the buffer was a distinct component of the claimed formulation under the Court's Becton precedent). The District Court decided that Becton controlled and Amgen had raised "a substantial question of noninfringement" that precluded Regeneron from demonstrating there was a likelihood of success on the merits for its infringement action. On this basis, the District Court denied Regeneron's motion for a preliminary injunction and this appeal followed.
The Federal Circuit affirmed, in a decision by Judge Lourie joined by Chief Judge Moore and Judge Stark. The panel relied not only on Becton but on follow-on cases coming to the same conclusions, including Kyocera Senco Indus. Tools Inc. v. Int'l Trade Comm'n, 22 F.4th 1369, 1382 (Fed. Cir. 2022), and Schindler Elevator Corp. v. Otis Elevator Co., 593 F.3d 1275, 1282 (Fed. Cir. 2010), on the principle that where a claim recites limitations separately the clear implication is that each recited limitation is a "distinct component" of the claimed invention. Reviewing how the District Court applied this principle, the panel asserted that "claim 1 plainly recites a pharmaceutical formulation, comprising four separately listed components." (The opinion in a footnote is careful to say that this is not a per se rule but raises a presumption that "may always be rebutted in the context of a particular patent," citing Google LLC v. Ecofactor, Inc., 92 F.4th 1049, 1058 (Fed. Cir. 2024).)
Here, the panel found that the plain meaning of the claims raises the "separate elements" presumption, and the opinion states that Regeneron's arguments to the contrary are "misplaced." In particular, the Court rejected Regeneron's argument that the District Court's previous construction of the term "buffer" with regard to the PI granted against Defendant Formycon precluded Becton from applying here. One basis for this decision was that the District Court in fact did apply established principles of claim construction, specifically Phillips v. AWH Corp., 415 F.3d 1303, 1316 (Fed. Cir. 2005) (en banc), to determine whether the elements are separate and that the buffer cannot be substituted with aflibercept.
In addition, the opinion states that the proper way to construe the claim is to determine "whether a formulation is claimed in a way that clearly implies it requires distinct components." Regeneron's proposed construction analysis was directed to whether the term "VEGF antagonist" overlaps with the term "buffer," the opinion saying that these inquiries are independent of each other. This assessment provided the Court another basis for rejecting Regeneron's argument that the prior construction from the Formycon decision should be binding.
Having concluded that the District Court properly applied Becton, the panel then turned to the evidence for whether Regeneron had rebutted the Becton presumption. The panel's basis for deciding that they had not done so began with the determination that the '865 patent's claims and the specification supported the District Court's decision that the terms at issue were separate. The opinion turned first to the claims, and the requirement for rebuttal that there was "evidence that shows that the impliedly distinct components, instead, can be satisfied by a single component" (the Court reminding that extrinsic evidence cannot alter the meaning found in the intrinsic evidence under Intel Corp. v. VIA Techs., 319 F.3d 1357, 1367 (Fed. Cir. 2003)). The panel found the intrinsic evidence supported the District Court's determination that the two claim elements were separate under Becton. This intrinsic evidence included the plain meaning of the claims, wherein all the '865 patent claims made the separateness distinction found by the District Court here, including the use of "different concentrations and different units of measurement" (emphasis in opinion). Turning to the specification, the panel agreed with the District Court that "the specification of the '865 patent uniformly describes the 'VEGF antagonist' and the 'buffer' as separate and distinct components of the formulation" (providing examples and in particular the lack of any instances where the buffering capacity of aflibercept was taught as a substitute for buffers disclosed therein). "'Nothing in the specification indicates' that the VEGF antagonist 'might' also satisfy the distinct 'buffer' component" according to the opinion.
Concluding their review of the intrinsic evidence considered by the District Court, the panel held that the lower court "correctly concluded that the only reasonable construction of the claim language, in light of the specification (which does nothing to rebut the presumption of separateness), is that the 'VEGF antagonist' and 'buffer' are distinct components."
The Federal Circuit then considered whether extrinsic evidence asserted by Regeneron rebutted the District Court's conclusions regarding Becton separateness of the recited elements, concluding that such evidence did not do so. The panel noted that the District Court could have refused to consider extrinsic evidence under the circumstances arising here where the intrinsic evidence is "clear and unambiguous." Having considered the extrinsic evidence presented by Regeneron "for completeness," the Federal Circuit found no clear error in the District Court's analysis that such evidence (consisting of expert testimony and citation of a prior art reference explaining the buffering capacity of polypeptides) did not rebut the Court's conclusions based on intrinsic evidence.
In sum, the Federal Circuit held that on this record there was "at least a substantial question of noninfringement" raised by Amgen's formulation differences and accordingly Regeneron had not established the requisite likelihood of success for the District Court to grant a preliminary injunction, citing as an example Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1364 (Fed. Cir. 1997).
It remains to be seen, of course, whether Amgen will launch "at risk" (that risk being a finding of willful infringement under 35 U.S.C. § 284 and enhanced damages including attorneys' fees for doing so). Under the circumstances behind the Federal Circuit's decision (including non-infringement) Amgen may decide it is worth the risk, which then raises the possibility that Regeneron will settle with Amgen or other defendants. Those decisions will likely be based on considerations to which others outside the parties are unlikely to be privy and thus remain to be seen.
Regeneron Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc. (Fed. Cir. 2025)
Panel: Chief Judge Moore and Circuit Judges Lourie and Stark
Opinion by Circuit Judge Lourie
Comments