Note: This post addresses two Federal Circuit decisions issued on January 29, 2025. Both appeals involved Plaintiff-Appellee Regeneron Pharmaceuticals, Inc., with the first appeal involving Defendant-Appellant Formycon AG (Case 24-2009) and the second appeal involving Defendant-Appellant Samsung Bioepsis Co. (Case 24-1965). At trial, each case also included Defendants Mylan Pharmaceuticals Inc., Amgen USA, Inc., Biocon Biologics Inc., Celltrion, Inc., and Amgen Inc., as well as the two Defendants-Appellants.
The Federal Circuit recently affirmed the District Court's grant of preliminary injunctions against each of the Defendant biosimilar applicants recited in the caption, as well as the District Court's finding of the court having personal jurisdiction over each, in two decisions captioned Regeneron Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc. (Fed. Cir 2025) having the Defendants-Appellants listed above.
The case arose in multidistrict litigation (28 U.S.C. § 1407) under the Biologics Price Competition and Innovation Act (BPCIA; 42 U.S.C. § 262(k)–(l)) over Regeneron's Eylea® (aflibercept) product. Aflibercept is a VEGF (vascular endothelial growth factor) antagonist (also termed a "VEGF trap") which is used to treat a number of angiogenic eye diseases including age-related macular degeneration (AMD) and diabetic retinopathy. Each of the Defendants had filed an Abbreviated Biologics License Application or were involved in the production of the biosimilar product for Eylea®, and at issue was Regeneron's U.S. Patent 11,084,865, specifically claim 4 as asserted against Samsung Bioepsis ("SB"):
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.
2. The vial of claim 1, wherein the concentration of said VEGF antagonist fusion protein is 40 mg/ml, and wherein said organic co-solvent comprises polysorbate.
4. The vial of claim 2, wherein said organic co-solvent comprises about 0.03% to about 0.1% poly-sorbate 20.
Also relevant to the proceedings was claim 5 of a related Regeneron patent, U.S. Patent No. 9,340,594, which was asserted by SB in arguing that the '865 patent was invalid under the judicially created doctrine of obviousness-type double patenting:
1. 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 [of] 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.
2. The pre-filled syringe of claim 1, wherein the first VEGF receptor is Flt1, and the second VEGF receptor is Flk1 or Flt4.
3. The pre-filled syringe according to claim 2, wherein the VEGF trap is stable for at least 4 months.
4. The pre-filled syringe according to claim 3, wherein the VEGF trap consists of amino acids 27-457 of SEQ ID NO:4.
5. The pre-filled syringe according to claim 4, wherein the stable ophthalmic formulation comprises 40 mg/mL of the VEGF trap, 10 mM phosphate, 40 mM NaCl, 0.03% polysorbate 20, 5% sucrose, at pH 6.2-6.4.
(in each instance the opinion sets forth relevant claim limitations in italics).
The District Court granted a preliminary injunction to Regeneron against SB preventing it from selling or offering to sell its FDA-approved aflibercept biosimilar product without a license from Regeneron. The District Court rejected SB's arguments to the contrary, based on Acorda Therapeutics Inc. v. Mylan Pharmaceuticals Inc. SB appealed, based on its assertions that the District Court improperly found personal jurisdiction in the multidistrict forum (the District of West Virginia) and improperly granted the injunction over its assertion that the '865 patent was invalid for ODP, failure to satisfy the written description of 35 U.S.C. § 112(a), and for failing to establish a "causal nexus" between its infringement and irreparable harm to Regeneron.
The Federal Circuit affirmed, in an opinion by Judge Taranto joined by Chief Judge Moore and Judge Reyna. The opinion relied on Merial Ltd. v. Cipla Ltd. for making its jurisdiction determination, setting forth the "two inquiries" under Federal Rule of Civil Procedure 4(k)(1)(A), upon which such determinations are made: first, "whether a forum state's long-arm statute permits service of process, and whether the assertion of jurisdiction would be inconsistent with due process," citing Electronics for Imaging, Inc. v. Coyle (finding that the West Virginia "long arm" statute is co-extensive with due process under In re Celotex Corp.). SB had argued that it lacked the "minimum contacts" required for a district court in a forum state to exercise jurisdiction, International Shoe Co. v. Washington, and that "there is no evidence that it plan[ned] to commercialize [aflibercept biosimilar] in West Virginia. Regeneron countered that "filing of its aBLA, serving of its Notice of Commercial Marketing, failure to deny the allegation that it would commercialize . . . in West Virginia through Biogen, and establishment of a robust distribution channel that includes West Virginia" was sufficient, and the Federal Circuit agreed.
Turning to Acorda, the panel set forth a comparison between the circumstances here and in that case, which involved ANDA litigation under § 271(e)(2) (the opinion noting that none of the parties argued that the jurisdictional standards were different between ANDA and BPCIA litigation). In Acorda, the ANDA filing, as "formal acts that reliably indicate plans to engage in marketing of the proposed generic drugs," was enough to establish personal jurisdiction in view of the Court's understanding that the Hatch-Waxman regime enacted by Congress illustrated an understanding of the "close connection between an ANDA filing and the real-world acts that approval of the ANDA will allow and that will harm patent-owning brand-name manufacturers." As in Acorda, the panel recognized SB's behavior -- filing an aBLA, serving the Notice of Commercial Marketing under 42 U.S.C. § 262(l)(8)(A), engaging with "several manufacturing, testing, labeling, and/or packaging partners," and entering into an "elaborate distribution agreement with Biogen" -- were consistent with the intent to sell its FDA-approved aflibercept biosimilar product in the forum state (the extent of SB's involvement with Biogen regarding distribution being particularly significant to the Court). Also significant was the lack of any evidence that the nationwide distribution network had any provisions for states where SB's product would not be sold, the panel holding that the District Court had not "clearly erred in finding that SB will retain a significant role in Biogen's activities through contractually established mechanisms."
The panel expressly rejected SB's assertion that there is a "bright-line constitutional difference" between SB distributing its product itself and contracting with a third party (Biogen) to do so, based on Acorda. Also rejected was SB's argument that Regeneron bore the burden of producing affirmative evidence that SB would market its product in West Virginia, saying "there is simply no good reason, under the constitutional standard, for demanding such singling-out evidence as a substitute for persuasive evidence of nationwide targeting without a carve-out."
Turning to the grant of the preliminary injunction, the issue before the Court was whether SB raised a "substantial question as to the invalidity of the '865 patent for obviousness-type double patenting" over the '594 patent. The question concerned three limitations arising in claim 1 of the '865 patent and claim 5 of the '594 patent. These were: "(1) a very specific 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) a requirement that the VEGF antagonist is 'glycosylated'; and (3) a "vial." The first distinction that the District Court relied upon in finding no ODP was that the '865 patent claim required that at least 98% of the claimed VEGF antagonist retained the native conformation after storage at 5°C for two months, wherein claim 5 of the '594 patent merely required that the protein was "stable for at least four months." The District Court construed these limitations to be that the "stability requirement' in the '594 patent was "broader than, and not limited to," the stability requirement recited in the '865 patent, based in part on the disclosure of their shared specification. Further, the District Court held that the limitation in the '865 patent claim was "not inherent (and thus not anticipated by)" the '594 claim. Accordingly the District Court found that the '865 patent claim "was non-obvious because a relevant artisan would not have been motivated to arrive at this requirement with a reasonable expectation of success."
On appeal, SB argued that the stability recited in the '865 patent claim was an obvious variant because it is "simply an additional property of the composition." The specifically recited stability in the '865 patent claim was "encompassed by" the generic stability limitation recited in the '594 patent claim according to SB. The Federal Circuit held that these arguments "bypass the focused factual analysis of motivation and reasonable expectation of success" and were thus unpersuasive, for at least the reasons that SB did not support its assertion that the existence of an additional property was enough to defeat patentable distinctness and that the cases relied upon by SB (Sun Pharmaceutical Industries, Ltd. v. Eli Lilly & Co.; Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc.; AbbVie Inc. v. Mathilda & Terence Kennedy Institute of Rheumatology Trust; Geneva Pharmaceuticals, Inc. v. GlaxoSmithKline PLC) did not support their argument. Also, "domination" (of a genus claim over a species, for example) "by itself[] does not give rise to 'double patenting'" according to the opinion, citing In re Kaplan. The panel asserts that "[w]e are not persuaded that SB has put forth a substantial basis for questioning that the 98% native conformation limitation of claim 1 of the '865 patent makes the claim patentably distinct from claim 5 of the reference patent" including, inter alia, that SB did not challenge the District Court's claim construction (regarding the term "stable") nor several of the District Court's factual findings on motivation and reasonable expectation of success.
The opinion notes that this would be enough to affirm the District Court's decision, but further states that the panel agreed with the patentable distinction that the '865 patent specifies that the protein is glycosylated while the '594 claims are silent on this feature (encompassing both glycosylated and non-glycosylated forms) and that SB had presented no persuasive argument to overturn the District Court on this issue.
The panel then addressed SB's contentions that the '865 patent failed to satisfy the written description requirement of 35 U.S.C. § 112(a) (itself a question of fact for which the District Court's determinations were entitled to deference under the clear error standard). The limitations SB challenged in this regard were the glycosylation limitation, the upper bound of 98% stability, and the lower boundary of the stability requirement. Regarding the glycosylation limitation, the panel assessed the challenge using the rubric that "a disclosure must be considered as a whole" as the skilled artisan would consider it, and determine whether the specification "reasonably conveys possession" of the claimed invention, citing Allergan USA, Inc. v. MSN Laboratories Private Ltd. (emphasis in opinion). The District Court relied on specific portions of the specification that disclosed the glycosylated forms and the stability data, supported by expert testimony that the skilled worker would understand that what was taught was glycosylation of specific residues. The Federal Circuit opined that on this record they could find no clear error. Moreover, the panel also found no contradictions between the District Court's finding on ODP (which were limited to the claims) and the District Court's findings on the written description requirement (which was based on the disclosure in the specification). Regarding the upper stability boundary, the panel found no clear error by the District Court in relying on expert testimony (including SB's own expert), and for the lower boundary held that the District Court properly distinguished the precedent SB relied upon in making its arguments (including Indivior UK Ltd. v. Dr. Reddy's Laboratories S.A.).
Finally, the Federal Circuit addressed and rejected SB's arguments that Regeneron had not established a causal nexus between its infringement and irreparable harm. First, SB argued that its biosimilar was approved by FDA to require only 96% stability, which would not infringe the '865 patent claims. The panel asserted in response that "[t]here is no evidence that SB possesses or plans to sell or offer to sell a non-infringing biosimilar under its approved aBLA [and i]ndeed, the evidence in the record indicates otherwise," citing expert testimony including that SB could not alter its FDA-approved formulation to be non-infringing with any guarantee that such a product would work as intended. Second, SB argued that the nexus required is that the stability feature of retaining 98% native conformation "must drive demand" for its product to establish such nexus. The panel stated that the precedent properly interpreted limits the causal nexus inquiry as argued by SB to "'complex, multi-featured' products," in instances where "a court must analyze whether the patented feature is a driver of consumer demand for the accused infringer's product," citing Apple Inc. v. Samsung Electronics Co. In contrast, for cases like this one, for "a product that essentially is the claimed invention" the causal nexus assessment is not required to establish irreparable harm according to the opinion (emphasis in opinion). In closing, the panel noted that "if SB produces a noninfringing product within the scope of its aBLA, it may seek modification of the injunction from the District Court.
The companion, nonprecedential decision (also written by Judge Taranto) relied on the Samsung decision for much of the background facts and arguments. The District Court in this case held that personal jurisdiction arose for Defendant Formycon and issued a preliminary injunction against this defendant; Formycon appealed both decisions.
Like Samsung Bioepsis, on the personal jurisdiction issue, Formycon argued that it has no "direct" ties to the forum (West Virginia), including being "not registered to do business there; ha[d] not appointed an agent for service of process there; ha[d] no assets or employees there; ha[d] not previously been sued there; and ha[d] not developed, manufactured, or packaged its drugs there" and also "has no plans or rights to itself commercialize (market and distribute)" its FDA-approved aflibercept biosimilar product there. Instead, a yet unnamed third party would be engaged to commercialize the drug for U.S. sales (including in West Virginia). But as described in the opinion, Formycon will not step away from commercialization efforts, and through "various contracts" will have "continuing rights and responsibilities regarding" its biosimilar product. The opinion states that the evidence as a whole showed Formycon planned to market its product in the U.S., including West Virginia, constituting affirmative acts such as filing its aBLA, serving Regeneron with a Notice of Commercial Marketing and engaging companies to "manufacture, package, and label" its biosimilar product in the U.S. In its efforts to establish a "distribution channel" for its product, the opinion states, Formycon has taken no steps to exclude West Virginia. While a separate corporate entity will "market, sell, and distribute" the product, Formycon through a supply agreement will make the FDA-approved aflibercept biosimilar product. The Federal Circuit "on the record as a whole" sees no difference between the SB and Formycin situations with regard to the personal jurisdiction question.
Regarding whether the District Court had improperly granted the preliminary injunction against Formycon, the panel asserts that the same bases for denying SB's invalidity contentions applied to Formycon (in the Samsung case the opinion asserts "we agreed with the district court on the [insufficiency of SB's ODP assertions based on the] first two [claim] limitations, and that agreement sufficed to affirm the district court's ruling on the ODP defense without our reaching the other issues. We do the same here"). And Formycon's "only argument arguably falling outside the category ("with respect to the 98% native conformation limitation")" also fails, according to the opinion, inter alia, because Formycon did not challenge the claim construction on which the District Court based its opinion ("The point is forfeited"). The Federal Circuit found no reversible error in the District Court's rejection of Formycon's ODP-based challenge to the District Court's grant of a preliminary injunction on the stability limitation, and as in its Samsung opinion assessed the glycosylation argument (albeit addressing a more detailed argument and additional bases for Formycon's contentions) and yet arrived at the same conclusion in rejecting it.
Similarly, the Federal Circuit did not see any "material difference between Formycon's arguments and those presented by SB" with regard to invalidity for failure to satisfy the written description requirement, and "Formycon has presented no argument we have not already considered and rejected in the SB decision" on the question of a lack of causal nexus between Formycon's infringement and irreparable harm to Regeneron in the absence of the injunction granted by the District Court.
Regeneron Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc. (Fed. Cir. 2025)
Nonprecedential dispostion
Case 24-2009 involving Defendant-Appellant Formycon AG
Panel: Chief Judge Moore and Circuit Judges Reyna and Taranto
Opinion by Circuit Judge Taranto
Regeneron Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc. (Fed. Cir. 2025)
Case 24-1965 involving Defendant-Appellant Samsung Bioepsis Co.
Panel: Chief Judge Moore and Circuit Judges Reyna and Taranto
Opinion by Circuit Judge Taranto
[View source.]
