UPC Court of Appeal adopts a ‘holistic’ approach to assessing inventive step in Amgen v Sanofi
In a significant judgment handed down in respect of Amgen’s European Patent EP3666797, which is a member of a patent family at the core of ongoing global litigation, the UPC Court of Appeal (CoA) has clarified in Amgen v Sanofi & Regeneron the legal test for assessing the inventive step of an invention and endorsed a ‘holistic’ approach to doing so.
This framework is considered less strict than the ‘problem-solution approach’ used by the European Patent Office (EPO) and is more aligned, for example, with the UK’s approach to evaluating obviousness.
Though the framework does still retain flavours of the problem-solution approach – for example, the framing of a technical problem that the skilled person is seeking to solve – this disparity opens the possibility of divergence between decisions issued by the EPO and the UPC in their assessment of the same patent claims.
Previously, in July 2024 the UPC’s Munich Central Division had ruled at first instance that EP3666797, which covers anti-PCSK9 antibodies (including Amgen’s Repatha® and Sanofi and Regeneron’s Praluent®) that can prevent or reduce the binding of PCSK9 to low density lipoprotein receptor (LDLR) for use in treating or preventing hypercholesterolemia or related diseases, lacked an inventive step.
This is because the Central Division held that the skilled person would have been motivated to develop antibodies binding to PCSK9 because this was suggested by the prior art, and that it would have required only routine experimentation to provide an anti-PCSK9 antibody as claimed. It was deemed irrelevant whether the skilled person would have had a ‘reasonable expectation of success’ of arriving at a therapeutically effective antibody.
As reported at the time, the decision subsequently led to the patent’s revocation across UPC Member States and a stay in Amgen’s infringement action against Sanofi and Regeneron.
However, the CoA has now overturned that revocation. In joint decisions issued on 25 November 2025 (UPC_CoA_528/2024 and UPC_CoA_529/2024), the CoA held that EP3666797 is in fact valid i.e. novel and inventive.
The judgment is notable, not just for the reversal of the decision issued at first instance but because it clarifies how UPC divisions should assess inventive step, especially in biotechnological and pharmaceutical cases. Though the holistic framework was first applied in Edwards v Meril, the CoA has further expanded on how a reasonable expectation of success is to be evaluated in the context of medical use claims.
Under the framework, the CoA emphasised the use of a ‘realistic starting point’, as opposed to the EPO’s approach of identifying the ‘closest prior art’, and considered what the skilled person would have done instead of what they could have done when faced with the technical problem to be solved, noting:
“This must be done by establishing what the invention adds to the state of the art, not by looking at the individual features of the claim, but by comparing the claim as a whole in the context of the specification and the drawings, thus also considering the inventive concept underlying the invention (the technical teaching), which must be based on the technical effect(s) that the person skilled in the art, on the basis of the application, understands is (are) achieved with the claimed invention.”
The CoA stated that determination of a realistic starting point should not be made with the benefit of hindsight, noting that there can be more than one realistic starting point but that the claimed invention must be inventive starting from each of them:
“A starting point is realistic if the teaching thereof would have been of interest to a person skilled in the art who, at the effective date, wishes to solve the objective problem. This may for instance be the case if the relevant piece of prior art already discloses several features similar to those relevant to the invention as claimed and/or addresses the same or a similar underlying problem as that of the claimed invention. There can be more than one realistic starting point and the claimed invention must be inventive starting from each of them.”
Identifying the technical problem as to “provide a therapeutically effective treatment or prevention of hypercholesterolemia or atherosclerotic disease or other conditions related to elevated serum cholesterol levels”, the CoA excluded from the formulation of the technical problem the concept of using PCSK9-binding antibodies per se to prevent pointers to the claimed solution and avoid hindsight.
The CoA considered the prior art – namely a scientific publication by Lagace et al describing PCSK9 as a target for lowering LDLR degradation – and concluded that it was not clear at EP3666797’s priority date whether using such antibodies would exert a therapeutic effect by lowering cholesterol levels.
The CoA did not consider it relevant that anti-PCSK9 antibodies could be developed by routine experimentation without inventive skill since the skilled person would not have set out to do so with a reasonable expectation of success that an antibody could be identified that achieved the claimed therapeutic effect.
The decision instead confirms that a claimed solution is obvious if the skilled person would have taken the next step in expectation of finding the solution to the technical problem, with the CoA ultimately finding – contrary to the first instance decision – that the claimed antibody is inventive:
“A reasonable expectation of success implies the ability of the skilled person to predict rationally, on the basis of scientific appraisal of the known facts before a research project was started, the successful conclusion of that project within acceptable time limits. Whether there is a reasonable expectation of success depends on the circumstances of the case. The more unexplored a technical field of research, the more difficult it was to make predictions about its successful conclusion and the lower the expectation of success. Envisaged practical or technical difficulties as well as the costs involved in testing whether the desired result will be obtained when taking a next step may also withhold the skilled person from taking that step. On the other hand, the stronger a pointer towards the claimed solution, the lower the threshold for a reasonable expectation of success.”
Meaningful guidance is also provided on issues of claim interpretation and sufficiency of disclosure of medical use claims, signalling that functionally defined claims (e.g. antibodies not defined by their exact amino acid sequences) can survive validity challenges at the UPC provided that the specification is sufficient and supports the claims.
Overall, the judgment seemingly constitutes the beginning of standardised practice at the UPC, providing a somewhat more flexible standard for evaluating inventive step by emphasising realistic starting points, ‘would vs could’ evaluation, and avoiding hindsight by careful problem formulation.
It also emphasises how quickly decisions can be issued by the UPC, which launched on 1 June 2023. Arriving two and a half years on from the UPC becoming operational, this decision is likely to be of keen interest to European practitioners, especially since the legal tests applied will likely need to be followed by all UPC Local and Regional Divisions moving forwards.
However, the litigation between the parties continues at pace, with the patent at issue currently under appeal at the EPO and with a hearing before Technical Board of Appeal 3.3.04 scheduled for April 2026. Watch this space.
Barker Brettell has a dedicated medical sector team who can assist and advise you on how to achieve the best protection for your innovation. To continue the conversation, please contact the authors of this article, Laura Riggall and Jennifer Atkinson, or your usual Barker Brettell attorney.
Published: December 2025
