A First Revocation Action from the UPC’s Central Division – Amgen Anti-PCSK9 Antibody Patent Held Invalid

In a recent decision in case 459505/2023 (UPC_1/2023), the UPC’s Court of First Instance (Munich Central Division) revoked Amgen’s EP3666797, relating to anti-PCSK9 antibodies. This decision was the Central Division’s first ever revocation decision and represents the latest in a long-running global dispute between Amgen, who market the cholesterol-lowering drug Repatha^®, and Sanofi/Regeneron, who market the drug Praluent^®.

The Central Division’s decision provides a further insight into the UPC’s handling of substantive issues, including claim interpretation and the assessment of inventive step. As discussed further below, the Central Division also considered substantive priority entitlement, referring to the EPO’s Enlarged Board of Appeal decision G2/98 and aligning with the EPO in relation to the “same invention”. With the Enlarged Board of Appeal of the EPO about to consider claim interpretation in light of the description, it will be interesting to see whether the opportunity is taken to harmonise on that point too.

With regard to inventive step, whilst so far neither the Court of Appeal nor the Central Division of the UPC has strictly applied the EPO’s (in)famous problem and solution approach there are clear similarities, including identifying the closest prior art document, considering the underlying problem and whether the claimed solution would have been obvious, including considering whether the skilled person would have had a reasonable expectation of success.

The Central Division’s decision also provides a first insight into how it may handle claims relating to antibodies.  The first indications are that the Central Division is following the EPO’s approach, where the development of antibodies to a known target is considered routine and non-inventive in the absence of any technical difficulties in producing such antibodies.

Background

EP3666797 (‘797) is part of a patent family comprising 13 divisional applications, originally stemming from EP2215124 (‘124). The ‘124 patent was granted with a main claim referring to an antibody binding to human PCSK9 that competes with specific reference antibodies and having neutralising activity. This claim was invalidated for lack of inventive step by an EPO Board of Appeal and ‘124 was ultimately maintained with sequence-based claims directed to specific antibodies.

The ‘797 patent

The ‘797 patent was granted with claim 1 directed to a monoclonal antibody or an antigen-binding fragment thereof for use in treating or preventing hypercholesterolemia or an atherosclerotic disease related to elevated serum cholesterol levels; or for use in reducing the risk of a recurrent cardiovascular event related to elevated serum cholesterol levels; wherein the monoclonal antibody or the antigen-binding fragment thereof binds to the catalytic domain of a PCSK9 protein of the amino acid sequence of SEQ ID NO: 1, and prevents or reduces the binding of PCSK9 to LDLR. In the UPC action the claimants challenged validity of this claim under various grounds, but the decision focuses on inventive step.

The Central Division’s decision

The Central Division start by setting out their interpretation of the claim, in particular the term “catalytic domain”. Reference is made to the framework set out by the Court of Appeal of the UPC in UPC_CoA_335/2023 (NanoString/10x Genomics). The Central Division state that “when interpreting a patent claim, the person skilled in the art does not apply a philological understanding, but determines the technical meaning of the terms used with the aid of the description and the drawings”. The Central Division also state that “the patent description may represent a patent’s own lexicon”. This provides further confirmation of the approach to claim interpretation that will be taken before the UPC.

The decision then includes discussion of substantive priority entitlement, relating to whether the term “catalytic domain” had changed in meaning between the third priority application and the application as filed. When considering priority entitlement, the Central Division refer to the test set out in the EPO’s Enlarged Board of Appeal decision G2/98, i.e. “a claimed invention is to be considered the same invention as the invention in a previous application if the skilled person can derive the subject-matter of the claim directly and unambiguously, using common general knowledge, from the previous application as a whole”. When applying this test, the patent was found to have a valid priority claim to the third priority application.

With regards to inventive step, the Central Division once again follow the framework set out by the Court of Appeal in NanoString/10x Genomics, taking the position that there may be several realistic starting points for the assessment of inventive step. Identification of the “most promising” starting point is not necessary. A claimed solution is then said to be obvious where the skilled person would have been motivated to consider the claimed solution and implement it as a next step.

The Central Division selected “Lagace” as the starting point for the assessment of inventive step. Lagace described the biological role of PCSK9, in particular that PCSK9 binds to and regulates levels of LDLR, a protein involved in the transport and breakdown of low-density lipoprotein cholesterol (LDL-C). Lagace also described how loss of PCSK9 had been shown to increase LDLR, thus lowering cholesterol levels. Lagace mentioned neutralisation of PCSK9 as a potential approach for the treatment of hypercholesterolemia.

According to the Central Division, “a claimed solution is obvious if the skilled person would be motivated to consider the claimed solution and would implement it as a next step in developing the prior art”. The Central Division also commented that any difficulties in taking these next steps may be indicative of an inventive step.

The Central Division considered that, following on from Lagace, the skilled person would have pursued antibodies blocking the PCSK9/LDLR interaction. The Central Division held that there were no serious obstacles and the skilled person would have arrived at suitable antibodies using routine methods and without any inventive skill. The ‘797 patent was therefore found to lack an inventive step and is therefore invalidated in all UPC states, although Amgen may appeal.

Final thoughts

Amgen have also filed a claim for infringement of the patent and the UPC’s local division in Munich will hear the parties later this year to decide whether to continue with the infringement proceedings, or to stay those proceedings pending the outcome of any appeal in the revocation action.

A further interesting point is that the ‘797 patent is the subject of parallel opposition proceedings at the EPO, with Amgen only recently filing their defence. No date for oral proceedings has yet been set. Accordingly, this also provides a demonstration of the relatively rapid nature of UPC proceedings. It will be interesting to see how the EPO’s opposition division react to the Central Division’s decision.

In summary, initial indications are that the UPC is following a similar approach to the EPO when considering antibody inventions, in particular taking the position that in the absence of technical difficulties generating antibodies to a known target would have been routine. However, further decisions will of course be needed to provide a more comprehensive picture.

J A Kemp is renowned and respected as one of the leading opposition practices in Europe and we are well placed to help clients navigate the early days of the UPC as the new court develops its procedures and case law.

With over 50 qualified UPC representatives, and with the appointment of intellectual property litigator John Hornby, our attorneys have the unique skills required for successful representation at the UPC. We are also able to handle parallel disputes in the EPO, UPC and UK courts, while also coordinating national actions across Europe.