News

On January 29, 2025, the CAFC issued opinions affirming the preliminary injunctions issued against biosimilars of Regeneron’s EYLEA® (aflibercept): Samsung Bioepis’s Opuviz™ (aflibercept-yszy) (CAFC Case Nos. 24-1965, 24-1966, 24-2082, 24-2083) and Formycon’s Ahzantive® (aflibercept-mrbb) (CAFC Case Nos. 24-2009, 24-2019, 24-2156), as well as the Court’s personal jurisdiction over Samsung Bioepis and Formycon (preliminary injunction district court opinions previously reported Preliminary Injunctions Issued Preventing Launch of EYLEA® Biosimilars).  The CAFC determined there was no reversible error in the holding that there was personal jurisdiction over the companies, or the holding that Regeneron had made out its affirmative case for preliminary injunctions, which included a determination that Samsung Bioepis and Formycon had not raised a substantial question of invalidity of Regeneron’s U.S. Patent No. 11,084,865 (“the ’865 patent”).

Personal Jurisdiction

With respect to personal jurisdiction over foreign companies Samsung Bioepis and Formycon, both argued that they did not have direct ties to West Virginia.  Both did not plan to market and distribute their biosimilars themselves, but instead signed agreements with Biogen (Samsung Bioepis) and Klinge Biopharma (Formycon) to commercialize their biosimilars.  The sales to the commercializing companies were to take place outside West Virginia, and Samsung Bioepis and Formycon argued that they did not have control over how the products were commercialized.

However, the CAFC found that the agreements signed with Biogen and Klinge did not terminate Samsung Bioepis and Formycon’s involvement at the time of sale, but instead gave them continuing rights and responsibilities regarding their biosimilars.  Samsung Bioepis’s rights included active participation in a joint steering committee composed of representatives from Samsung Bioepis and Biogen, and Formycon would be included in regular meetings and phone calls with Klinge regarding Ahzantive®‘s commercialization, liability for drug manufacture, technical release, packaging and testing, audits of a partner’s books and records, receipt of royalty payments, and mutual agreement on a launch date.

The CAFC also considered the fact that it was Samsung Bioepis and Formycon that filed the aBLAs and provided the Notices of Commercial Marketing to Regeneron.  Notably, the aBLAs did not identify any parts of the U.S. where Samsung Bioepis and Formycon do not intend to market or distribute Opuviz™ or Ahzantive®.  Under these facts, along with Samsung Bioepis and Formycon’s establishment of robust distribution channels that include West Virginia, the district court found, and the CAFC agreed, that the minimum-contacts standard was met.

The CAFC rejected Samsung Bioepis’s arguments that there is a difference between doing its own distribution and contracting with a national distributor (but remaining significantly engaged with that distributor) and the assertion that Regeneron needed to provide affirmative evidence of Samsung Bioepis or Biogen calling express attention to West Virginia as a target market.

Preliminary Injunction

  • Validity – Obviousness-Type Double Patenting

Samsung Bioepis and Formycon challenged the ’865 patent as being invalid for obviousness-type double patenting over another patent in the same family, U.S. Patent No. 9,340,594 (“the ’594 patent”), that had an earlier expiration date due to a terminal disclaimer.

The CAFC agreed with the district court that the claims of the two patents were patentably distinct, particularly as they related to stability of the “VEGF trap” (also known as “aflibercept”).  Where the ’865 patent had very specific stability and stability testing requirements at two months, the ’594 patent simply required the VEGF trap to be stable for at least four months, which the district court concluded was broader than and not limited to the stability requirement in the ’865 patent.

The CAFC noted that “the fact that the ’865 patent’s narrower stability limitation is ‘encompassed’ by the reference patent’s stability limitation does not change the outcome: We have made clear that ‘domination’—where one patent with a broader claim reads on an invention defined by another patent’s narrower claim, as a genus does a species, it ‘dominates’ the latter patent—’by itself[] does not give rise to ‘double patenting.’” (quoting In re Kaplan, 789 F.2d 1574, 1577 (Fed. Cir. 1986)).  Here, Samsung Bioepis and Formycon failed to show that this was a case where a species of a patented genus was not separately patentable.  The CAFC also rejected Formycon’s argument that some claim limits were inherent in the ’594 patent because Formycon did not challenge the district court’s claim construction that construed the ’594 reference patent’s “stable” limitation to be broader then the ’865 patent’s stability limitations.

Additionally, the CAFC agreed with the district court’s decision that the ’865 patent’s requirement that the VEGF trap be “glycosylated” made it patentably distinct, as the ’594 reference patent said nothing about glycosylation, and the district court construed it to embrace both glycosylated and non-glycosylated aflibercept.  A relevant artisan would not have been motivated to use the glycosylated version because the prior art showed it would have undesirable properties.

The CAFC also rejected Formycon’s argument that the “glycosylated” aflibercept was anticipated because aflibercept can only exist in either two states- glycosylated or not, so a relevant artisan would have been immediately able to envisage the entire genus.  The CAFC disagreed, finding this was not a very small genus, as there were at least five potential glycosylation sites, and at least 30 possible glycosylated forms of aflibercept, in addition to the nonglycosylated form.  The CAFC also found there to be no clear error in the district court’s analysis regarding Formycon’s various obviousness arguments, because the evidence sufficiently pointed toward a motivation to glycosylate.

  • Validity – Written Description

Samsung Bioepis and Formycon also challenged the ’865 patent’s validity for lacking adequate written description.  They argued that the district court erred in finding they had not raised a substantial question of invalidity because the ’865 patent’s specification does not adequately support the glycosylation, the upper bound of the “at least 98%” stability requirement, and the lower bound of that stability requirement in the challenged claims.

The CAFC rejected these arguments, finding that the specification did reasonably convey possession of the “glycosylation” term; that the upper bound of the stability requirement was supported with examples showing 99.3% purification and expert testimony that most proteins are not purified to 100%; and the lower bound was supported by multiple disclosures of native conformations throughout the range of 98% to 100%.

Causal Nexus Between Infringement and Irreparable Harm

The CAFC also rejected Samsung Bioepis and Formycon’s arguments that there was no causal nexus between Opuviz™’s / Ahzantive®‘s infringement and the irreparable harm that Regeneron would incur without injunctive relief.  It found that Samsung Bioepis and Formycon did not provide evidence that they planned to sell non-infringing biosimilars that are only 96% stable at two months, and that the infringing products did not have features relevant to consumers’ purchasing decisions other than what the patent claimed, so there was little causal nexus analysis that needed to be done.

Regeneron reported EYLEA® sales of $5.72 billion in 2023.

For more information about these and other biosimilar patent disputes, please visit BiologicsHQ.

 

_____________________________________________________

The author would like to thank April Breyer Menon for her contributions to this article.


    Methodology

    Information contained in the Venable BiologicsHQ database relates to FDA-approved drug products listed in the CDER Purple Book or on the FDA website (www.fda.gov). Information relating to FDA licensed products, FDA-approved indications, and aBLA and 505(b)(2) applications is obtained from public sources including the U.S. FDA website (www.fda.gov). Information relating to litigations is given only for cases active from January 31, 2010 onward. Information relating to foreign biosimilar / biologics follow-on products approved in Australia, Canada, the E.U., Japan and South Korea is from public sources. Statistics graphics are compiled from information contained in the Venable BiologicsHQ database.

    Disclaimer

    The individuals who maintain this site work for Venable LLP. The information, comments and links posted on this site do not constitute legal advice. No attorney-client relationship has been or will be formed by any communication(s) to, from or with the site and/or the author. For legal advice, contact an attorney at Venable LLP or an attorney actively practicing in your jurisdiction. Do not send any confidential or privileged information to the author; neither Venable LLP nor the author will assume any liability or responsibility for it. If you send any information, documents or materials to the site, you give permission for the author to include them on or in the site. No information, documents or materials you send to the site will be considered confidential or privileged by Venable LLP or its lawyers. Also, no such information, documents or materials will be returned to you. All decisions relating to the content belong to the author.

    Subscribe for Future Updates

      captcha