Infringement by equivalence: When the doctrine of equivalents doesn’t quite line up

Diverging approaches before the EWHC and Munich Regional Court I highlight persisting uncertainty over infringement by equivalence in the pharma field. By Dr Claire Irvine (Fellow).

In October 2025, written judgments were issued by both the EWHC and the Munich Regional Court I as part of the on-going multi-jurisdictional litigation arising from the wish of Formycon to market biosimilars of Regeneron’s aflibercept formulation (marketed under the brand name Eylea) for treatment of wet AMD. Of particular interest is that the judgments of both courts addressed infringement by equivalence of the same formulation patent, Regeneron’s EP2364691B, but came to opposite conclusions – positive in the case of the Munich court but negative in the case of the EWHC.

In issuing and then maintaining a cross-border preliminary injunction against Formycon affecting 19 EPC countries (supplementing a preliminary injunction effective for Germany alone), the Munich court firstly saw justification in this being a procedural matter aligning with the CJEU’s landmark decision re cross-border jurisdiction in BSH Hausgeräte v Electrolux. Moreover, in justifying reliance on infringement by equivalence, the relevant judgment states that cross-border effect is justified in its entirety

‘because, based on the establishment of equivalent patent infringement in Article 2 of the Protocol to Article 69 EPC, it can be assumed that the same standards apply in all countries with regard to the requirements for accepting equivalent patent infringement. Therefore, the assessment that a patent infringement by equivalent means exists under German law serves as a guideline for other EPC states. The defendants have not succeeded in demonstrating that a different standard applies in any of the aforementioned states.’

How then to deal with the fact that the EWHC issued a written decision on 8 October 2025 appearing to contradict this? The German judges fortunately had time ahead of issuing their written reasoning to include a comment on this and attempt to down-play the contradictions in the conclusions on infringement. This was aided by the fact that:

different claims were the focus of consideration, claim 1 as amended to ‘for use’ form before the Munich court and a narrower dependent claim 5 before the EWHC; and
more extensive proceedings before the EWHC including hearing of expert witnesses with a holding additionally of validity.

Nevertheless, difference in approach can be seen despite both judgments referencing the pemetrexed litigation which had the same result in both jurisdictions – a claim referring to pemetrexed disodium did not exclude alternative use of the dipotassium salt.

The background to the aflibercept litigation

SPC coverage for aflibercept itself, a fusion protein which targets vascular endothelial growth factor (‘VEGF’), was due to shortly expire. The EWHC judgment related to the trial of two actions concerning two European patents (UK) of Regeneron, EP2364691B (the ‘691EP) and EP2944306B (the ‘306EP), relating to formulation of aflibercept for intravitreal injection to the eye. These patents are from the same family. The ‘691EP was not opposed at the EPO. At the time of the EWHC judgment, the ‘306EP had been found invalid by the EPO Opposition Division and was subject to EPO appeal proceedings.

Formycon (together with its commercialisation partner) and separately Samsung Bioepis sought revocation of both the ‘691EP and ‘306EP before the EWHC. Regeneron and its European licensee (collectively referred to herein as Regeneron) accepted that there was no infringement as a matter of normal interpretation but counterclaimed for infringement by equivalence.

Before the Munich court, infringement by equivalence in relation to the ‘691EP was the sole matter relied upon by Regeneron in preliminary injunction proceedings. Before both courts, the only biosimilar formulation feature to be considered was substitution of 10 mM sodium phosphate by 10 mM histidine, a recognised alternative buffer for pH control.

The EWHC negative finding in relation to claim 5

Before the EWHC, Regeneron chose to rely on dependent claim 5 as granted but subject to unconditional proposed amendment:

‘An ophthalmic formulation according to claim 1 comprising
(a) 10 mg/l or 40 mg/ml of a VEGF antagonist consisting of amino acids 27-457 of SEQ. ID. No: 4, which is glycosylated at Asn residues 62, 94,149, 222 and 308;
(b) 0.03% of polysorbate 20;
(c) about 40 mM sodium chloride;
(d) 10 mM of sodium phosphate buffer; and
(e) 5% sucrose,
wherein the pH of the formulation is pH 6.2-6.3.’

This meant that arrival at Fomycon’s biosimilar compared to the claimed formulation merely required the precise feature (d) buffer substitution as noted above.

The judge in considering infringement by equivalence necessarily started from the three questions set by the UK Supreme Court in Actavis v Lilly [2017] UKSC 48 concerning pemetrexed (referred to in the judgment as Actavis Q1, Q2 and Q3):

‘i) Notwithstanding that it is not within the literal meaning of the relevant claim(s) of the patent, does the variant achieve substantially the same result in substantially the same way as the invention, i.e. the inventive concept revealed by the patent?
ii) Would it be obvious to the person skilled in the art, reading the patent at the priority date, but knowing that the variant achieves substantially the same result as the invention, that it does so in substantially the same way as the invention?
iii) Would such a reader of the patent have concluded that the patentee nonetheless intended strict compliance with the literal meaning of the relevant claim(s) of the patent was an essential requirement of the invention?’

Significantly, the judge took up in part argument of Regeneron that faced with the task of formulating a therapeutic protein for a specific delivery route not only buffering but overall required stability are considerations. This was conceptualised as the role of excipients being considered at two levels:

‘The first level is that each component performs its primary function; the surfactant prevents aggregation, the buffer maintains pH,and so on. The second level is that the components all together interact so that the total formulation is stable.’

While the judge regarded the ‘second level’ concept as driven by thought of obviousness attack, he saw it as reflecting scientific reality:

‘It will be apparent that the first level is easy to understand and explain (and if the first level was all that there was to it the formulation aspects of the claims could well be obvious as just the unrelated use of CGK components for their individual CGK purposes- Regeneron meets such an attack by relying on the second level). By contrast the second is unpredictable and is where the empirical nature of the work comes in. Even after the skilled team knows the total formulation is stable they will not understand this second level and how the excipients, at the molecular level of extremely fine detail, are interacting to allow stability to be maintained. I agree that these two levels reflect scientific reality and were CGK [emphasis added].’

It was this second level stability point that led the judge to refute infringement on the basis that the inventive concept for consideration of Actavis Q1 should be seen as narrow and not ignoring the specified excipients of claim 5. The specification made no reference to histidine. Furthermore, the judge considered that Actavis Q2 had to be answered ‘yes’ without need for further investigation.

The Munich court focus on the ‘level 1’ role of the buffer

The Munich court was concerned with joined preliminary injunction hearings over a day and thus certainly did not have the total input of expert witnesses and extensive argumentation of the 11-day hearing before the EWHC in which Regeneron was also defending validity. Nevertheless, as regards consideration of infringement by equivalence exactly the same buffer substitution was the matter for consideration as seen through the eyes of the skilled person. The claim under consideration was in ‘for use’ format with ranges for each component, including a range of 5-40 mM sodium phosphate buffer (although the exemplification for this buffer remained confined to 10 mM).

The judgments refer to the established case law of the Federal Court of Justice on the conditions to be met for infringement by equivalence (the Schneidmesser test):

Equivalent effect of the means: Does the contested embodiment solve the problem underlying the invention by means that are modified but objectively equivalent in effect?
Findability of the means having the same effect: Does their technical knowledge enable the skilled person to find the modified means as having the same effect?
Equivalence of the modification: Are the considerations that the skilled person must make so orientated towards the meaning of the technical teaching protected in the patent claim that the skilled person considers the deviating embodiment with its modified means to be the equivalent solution in question?
Furthermore, it must be examined whether the patent holder deliberately excluded certain embodiments from the scope of protection and whether the so-called ‘form stone objection’ precludes the assumption of infringement by equivalent means?

Yes, different questions from the UKSC Actavis questions but before both courts statements made on behalf of Regeneron during EPO examination concerning perceived aesthetic problem with histidine use were held of no import; the different finding of the Munich court on infringement by equivalence might be seen as residing in two factors:

Factor 1: focusing on substitution of the buffer for pH control ahead of any consideration of stability
Factor 2: the findability consideration does not exclude further investigation of stability achievement.

It is notable that the cross-border PI judgment suggests that conformity in application of Article 2 of the Protocol to Article 69 EPC across EPC states also demands conformity of facts before relevant courts – the EWHC had a different case content after hearing expert witnesses. However, it is equally notable that the Munich court decision does not exclude mention of stability – just applies need for this as a secondary issue which can be tested and does not affect that histidine buffer was a recognised buffer that might be substituted for sodium phosphate for pH control purpose.

The judges saw as highly pertinent that the end of paragraph [0047] of the patent explicitly indicated the purpose of the phosphate component as adjustment of pH with only sodium phosphate being mentioned. They also noted that at the priority date histidine buffer had been disclosed for use in formulation of a different therapeutic for the same ophthalmic purpose. Moreover, CGK on pH range buffering by sodium phosphate and histidine was held to reinforce indication to the skilled person that they may be considered alternatives. On this factual foundation, it was held that replacement of sodium phosphate buffer according to feature 1.4 of the claim by histidine buffer met the first step of examination for equivalence.

Significantly, as regards criterion 2 (the findability criterion), they held:

‘The second question must also be answered in favor of the plaintiff. At the time of the priority, the buffer histidine, which can be used for protein formulations, was available to the skilled person as an agent with the same effect instead of sodium phosphate. This discovery does not itself require any inventive step on the part of the skilled person (see Meier-Beck, GRUR 2003, 905, 909). The necessity of routine experiments does not exclude the absence of inventive step.’

As regards Factor 2, the Munich court PI judgments go on to state:

‘It is common general knowledge among those skilled in the art that a formulation is composed of various components and that these are fundamentally interchangeable. However, there is no guarantee that the overall formulation will still have the desired properties after the exchange. In this respect, further tests will always be necessary, which fall within the scope of the usual practice of the skilled person [emphasis added].’

Conclusion

It follows that a difference of approach can be seen. Nevertheless, a subsequent request before the Munich Regional Court I for negative declaratory action with request for reopening of oral proceedings based on the EWHC judgment failed. The resulting injunction decision states:

‘There was no reason to reopen the oral proceedings, as the Chamber has taken the judgment into account in its decision.’

It remains to be seen if appeal of the EWHC decision will bring the conformity of application of Article 2 of the Protocol to Article 69 EPC the Munch Regional Court I asserted should apply in all EPC states.

Fuller report of the EWHC decision is to be found in the UK court report section of the November issue of the CIPA Journal.

Dr Claire Irvine, Beck Greener LLP with thanks to Dr. Ulrich Storz, Senior Partner, Michalski Hüttermann & Partner Patentanwälte mbB for notification of the decisions of the Munch Regional Court I and comments.

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