Completing a recent jurisprudential "hat trick,"* the Federal Circuit affirmed a District Court grant of a preliminary injunction against a biosimilar applicant for Regeneron's EYLEA biologic drug in Regeneron Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc.
As in the earlier appeals, the injunction was based on infringement by Celltrion's EYLEA biosimilar (designated CT-P42) of U.S. Patent No. 11,084,865 and the appeal limited to the propriety of the District Court granting a preliminary injunction (PI) to Regeneron (as well as some jurisdictional issues). The opinion dealt summarily with those issues resolved in the earlier appeals, including whether the District of West Virginia could exercise jurisdiction against Celltrion, a Korean company. Based on the Court's earlier decisions, in this opinion the panel held that Defendant-Appellant Celltrion had sufficient minimum contacts with the West Virginia forum to satisfy the jurisdictional standard in the Fourth Circuit. The opinion also set forth the Court's determination that Regeneron satisfied its burden for being granted a PI, specifically that "(1) it is likely to succeed on the merits, (2) it is likely to suffer irreparable harm in the absence of preliminary relief, (3) the balance of equities tips in [its] favor, and (4) an injunction is in the public interest," citing BlephEx, LLC v. Myco Indus., Inc., 24 F.4th 1391, 1398 (Fed. Cir. 2022). Once again, the panel held that questions of the nexus between Celltrion's sales of its EYLEA biosimilar and irreparable harm to Regeneron had been established in the earlier appeals and applied here.
The only issue recognized by the Federal Circuit to be before it in this appeal was whether Celltrion had raised a "substantial question of invalidity" against Regeneron's '865 patent, specifically on obviousness-type double patenting (ODP) grounds. This challenge was based on Claim 5 of an earlier-issued Regeneron patent, U.S. Patent No. 9,340,594:
5. [A pre-filled syringe suitable for intravitreal administration comprising a 1 mL luer glass syringe fitted with a plunger and a stable ophthalmic formulation of a vascular endothelial growth factor (VEGF) trap, which consists of (i) a receptor component consisting essentially of an immunoglobulin-like domain 2 of a first VEGF receptor and an immunoglobulin-like domain 3 of a second VEGF receptor, and (ii) a multimerizing component, wherein the stable ophthalmic formulation comprises:
(a) 1-100 mg/ml a VEGF antagonist;
(b) 0.01-5% of one or more organic co-solvent;
(c) 5-40 mM of buffer; and
(d) optionally comprising 1.0-7.5% of a stabilizing agent[,
wherein the first VEGF receptor is Flt1, and the second VEGF receptor is Flk1 or Flt4, wherein the VEGF trap is stable for at least 4 months, and] wherein the VEGF trap consists of amino acids 27-457 of SEQ ID NO:4, wherein the stable ophthalmic formulation comprises 40 mg/mL of the VEGF trap, 10 mM phosphate, 40 mM NaCI, 0.03% polysorbate 20, 5% sucrose, at pH 6.2-6.4,
Wherein the italicized limitations were recited in independent claim 1 and intermediate dependent claims 2 through 4.
The District Court had held that the patentable distinctions between this claim and the claims of the '865 patent included "(1) the stability requirement that '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'; (2) the requirement that aflibercept [the EYLEA active ingredient] is glycosylated; and (3) the use of a vial versus a pre-filled syringe." The panel set forth in the opinion the specific distinctions between claim 5 and claim 4 of the '865 patent to be that claim 5 requires stability of the VEGF trap to be maintained for "at least 4 months," whereas claim 4 of the '865 patent recites that "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." The District Court concluded (and the Federal Circuit agreed) that the 98% limitation was "neither inherent nor obvious" in what was claimed in claim 5 of the '594 patent. Celltrion's specific challenges to this determination were the District Court's claim construction of the term "stable," wherein the District Court did not construe the term to mean the specific requirement recited in claim 4 of the '865 patent, instead holding that the term "stable" had "a broader meaning than the particular SEC measurements of aggregation and threshold levels (98%) to which Celltrion attempts to limit the term." The District Court rejected Celltrion's assertions that such stability was sparsely reported in the '594 specification, finding "numerous descriptions of stability beyond simply 98% native conformation as measured by SEC." The Federal Circuit agreed with the District Court's construction of the term "stable" and accordingly rejected Celltrion's argument that claim 5 of the '594 patent "expressly anticipates the stability limitations in the asserted claims [of the '865 patent]."
Celltrion's second challenge was that the "98% native conformation claim limitation" in claim 4 of the '865 patent was inherent in the stability limitation recited in claim 5 of the '594 patent. According to the District Court:
Celltrion's reliance on the native conformation data in Examples 3 and 4 [of the '594 patent] is legally inadequate to prove inherency. That the practice of '594 claim 5 sometimes results in 98% native conformation is insufficient; inherency requires that the 98% native conformation limitation be present necessarily, not just possibly or probably [emphasis in original].
The Federal Circuit rejected as a contradiction of the plain meaning of the claims Celltrion's arguments that the skilled artisan would have interpreted the stability limitations of "at least 98% [to] define[] a rate of aggregation over a particular time, under particular conditions" because the claim recites that the 98% of the VEGF antagonist be "present in native conformation following storage . . . for two months" which in no way implicates calculation of a rate of aggregation as argued by Celltrion.
Third, the panel rejected Celltrion's argument of error by the District Court in deciding that the 98% native conformation limitation was not obvious, which was based on expert testimony.
Finally, the Court briefly turned to Celltrion's arguments regarding the glycosylation limitations, which the District Court had rejected based on the extent of glycosylation of aflibercept. Celltrion argued that claim 5 of the '594 patent anticipated the asserted claims of the '865 patent because it covers "a genus with only two species – glycosylated and non-glycosylated." The District Court held that, in view of the "five distinct glycosylation sites," "there are at least thirty possible glycosylated forms of aflibercept . . . in addition to the nonglycosylated form." In view of the Court's determination that "one patentably distinct limitation [i.e., the stability limitation] is enough" to support the District Court's rejection of Celltrion's assertion of invalidity for ODP, and Celltrion's opportunity to pursue this invalidity argument at trial, the Court held that there was no need to address the issue here and affirmed the District Court's determination that Celltrion had not rebutted Regeneron's evidence of there being a likelihood of success on the merits to support its motion for a preliminary injunction.
Trial against this defendant, and the remaining defendants** is ongoing.
* See "Regeneron Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc. (Fed. Cir. 2025)" and "Regeneron Pharmaceuticals, Inc v. Formycon AG"
** In addition to Mylan Pharmaceuticals Inc. and Formycon AG these include Amgen USA, Biocon Biologic Inc., Samsung Bioepsis Co. Ltd, and Amgen Inc.
Regeneron Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc. (Fed. Cir. 2025)
Nonprecedential disposition
Panel: Circuit Judges Prost, Wallach, and Chen
Opinion by Circuit Judge Prost
[View source.]
