Formycon and Samsung Bioepis succeed against Regeneron in latest examination of the doctrine of equivalents

Formycon AG, Samsung Bioepis (UK) Limited & ors. v Regeneron Pharmaceuticals, Inc. & anr. [2025] EWHC 2527 (Pat).

Regeneron’s product Eylea is a formulation of aflibercept, an inhibitor of vascular endothelial growth factor (VEGF). VEGF is a naturally occurring signal protein produced in the body to promote the formation of blood vessels. The inhibition of its action in the eye can be desirable in the treatment of certain forms of macular degeneration involving abnormal growth of blood vessels into the macula, causing vision loss.

Eylea is protected by an SPC covering the underlying aflibercept European patent. The SPC will expire on 22 November 2025 leaving Regeneron with only secondary patents to prevent generic market entry, including formulation patents. This trial concerned two such formulation patents, EP 2 364 691 (EP ‘691) and EP 2 944 306 (EP ‘306), essentially identical but for the delivery method – one of the patents involving a prefilled syringe. The generic parties in this trial, Formycon and Samsung Bioepis, had each developed biosimilar aflibercept products and brought separate claims for declarations of non-infringement and revocation of the patents. Regeneron in turn counterclaimed for infringement.

Regeneron characterised the inventive concept of the patents as simply the precise formulation claimed – and pleaded that each specific excipient provided a certain functionality. In closing submissions, Mr Speck KC for Regeneron characterised these as the “primary functions” of the excipients, contrasting with potentially undesirable secondary effects. Neither of the generic products comprised the precise combination of the claims – Formycon’s formulation used a histidine buffer in place of the claimed sodium phosphate; and Samsung Bioepis’ formulation lacked the claimed sodium chloride tonicity agent replacing it with increased levels of sucrose stabilising agent.  During the course of the trial, it became clear that the basic knowledge that a stable formulation of aflibercept would require certain categories of excipient was found in the prior art. This left Regeneron to argue infringement by equivalence on the basis that knowledge of the claimed formulation would impart upon the skilled person a “degree of predictability” in determining whether alternative formulations would be likely to work.

In relation to Formycon’s formulation, Mr Speck suggested the presence of the sodium phosphate buffer would indicate to the skilled person that they would be able to substitute alternative buffers and still produce a stable formulation. The judge rejected an argument advanced by Charlotte May KC for Formycon that because histidine was a known CGK buffer, it followed that the patentee had obviously made a conscious decision not to claim it. Instead, in finding the patents not infringed by the Formycon product, the judge considered that Regeneron’s equivalence argument fell at the first Actavis question – a histidine buffer does not achieve the same result (stability) in substantially the same way as a sodium phosphate buffer because the inventive concept must be construed narrowly as requiring sodium phosphate.

The Samsung Bioepis product was found not to infringe, on the basis that the differences in the formulation meant that stability was not achieved in the same way as the formulation of the claims, and so infringement by equivalence also fell at the first Actavis question.

Underpinning the infringement decisions was the judge’s earlier conclusion on how to construe the inventive concept, and on what level of generality. The implication being that, had the inventive concept been construed at a higher level of generality, the answer to the first Actavis question might have been different. The judge considered the possibility that his view of the inventive concept was too narrow but nevertheless considered Regeneron’s case to fail, this time at Actavis question 3 – i.e. whether the patentee intended strict compliance with the claim. If the inventive concept is broad, but the claim language unambiguously narrow, that would tend to indicate that the patentee had made a positive choice (potentially to avoid prior art) and intended strict compliance.

Ultimately, neither generic product was found to infringe and, additionally, EP ‘306 was held invalid for added matter.