UPC Court of Appeal tackles broad functional antibody claims (UPC_CoA_529/2024)

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Dec 1, 2025, 12:24:43 PM (3 days ago) Dec 1

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UPC Court of Appeal tackles broad functional antibody claims (UPC_CoA_529/2024)

Dr Rose Hughes Monday, December 01, 2025 - antibody inventions, inventive step, patents, PatKat, Rose Hughes, sufficiency, upc

The global litigation saga involving Amgen’s PCSK9 antibodies has long served as a high-stakes test case for jurisdictional approaches to broad, functionally defined antibody claims. Following the US Supreme Court’s landmark finding of lack of enablement in Amgen v Sanofi (IPKat), and the UPC Munich Central Division’s initial revocation of the equivalent European patent (IPKat), all eyes were on the UPC appeal. How would the UPC Court of Appeal approach the questions of the patentability standard for broad functional antibody inventions? We now have the answer. In short, the UPC CoA has followed an approach broadly similar to that of the EPO on both sufficiency and inventive step. Whilst the UPC CoA reverses the first instance decision finding a lack of inventive step, the court took pains to emphasise the fact-specific nature of its decision. For this Kat, the decision indicates a harmonious approach of the UPC and EPO to antibody inventions.

Amgen versus Sanofi in Europe: Case details

This case concerned Amgen’s patent EP 3666797 relating to anti-PCSK9 monoclonal antibodies for use in treating or preventing hypercholesterolemia or an atherosclerotic disease. Importantly, the contested claim defined the antibody solely by its function, and not by sequence or structure. Claim 1 of the patent as granted was as follows:

"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."

At first instance, the Munich Central Division revoked the patent, reasoning that since the target (PCSK9) was known, generating antibodies against it was a matter of routine for the skilled person (UPC_CFI_1/2023, IPKat). The Patentee, Amgen, appealed this decision, arguing that the court had applied the wrong legal framework regarding the reasonable expectation of success. The Respondents, Sanofi and Regeneron, cross-appealed, maintaining that the patent was invalid for insufficiency.

The patent in question is part of a family of Amgen patents subject to global litigation, and including the US patent revoked in the landmark US Supreme Court decision Amgen v Sanofi, in which the broad function claims were found to lack enablement (IPKat). The patent family is seen as an important test case for establishing jurisdictional approaches to functionally claimed antibody inventions. How then would the UPC Court of Appeal approach the issue?

Sufficiency: Reasonable trial and error does not equate to undue burden

On appeal, Sanofi argued that the patent was insufficient because the functional definition of the claim, that required binding to the catalytic domain and blocking the LDLR interaction, imposed an undue burden on the skilled person. Sanofi contended that the patent failed to teach how to produce the "full breadth" of antibodies covered.

Sanofi particularly pointed out expert submissions that there were agreed embodiments falling under the scope of the claim that would be very difficult to make, the so-called "EGFa mimics". The Respondents seized upon an inventor’s admission that generating antibodies binding to this specific region would be "tricky," and argued that this proved the "full breadth" of the claim was not enabled.

Undue experimentation?

However, the UPC Court of Appeal was not convinced by this argument. The Court noted that the patent disclosed several methods for identifying antibodies that bind to the catalytic domain, including X-ray crystallography and scanning mutagenesis. Whilst Sanofi argued that X-ray crystallography was onerous and unpredictable, the CoA dismissed this, noting that "occasional failure is part of scientific work" and that a reasonable amount of trial and error does not equal undue burden (Headnote 8; para. 115).

Furthermore, the CoA clarified that the non-availability of some embodiments was immaterial to sufficiency, provided that the skilled person could obtain suitable embodiments within the scope of the claim. In particular, the Court of Appeal did not equate "tricky" with "impossible" or an "undue burden" with respect to the claimed invention. The CoA found that a patent need not enable "each and every conceivable embodiment", such as the EGFa mimics in the case in question (Headnote 7; para. 117 and 118). For the CoA, provided that the skilled person was provided with at least one way to perform the invention and could obtain suitable embodiments within the functional scope, the non-availability of specific variants like EGFa mimics was immaterial to sufficiency.

The CoA concluded that the burden of proof thus lay with the Respondents to demonstrate that the skilled person would be unable to obtain antibodies with the claimed functional properties (Headnote 9). For the CoA, the Respondents had failed to discharge this burden and the insufficiency attack was dismissed.

UPC aligns with the EPO on the sufficiency standard for broad functional antibody inventions

For this Kat, comparisons of jurisdictional approaches to sufficiency (and other substantive aspects of patent law) are difficult to compare in the abstract. What the decision of the CoA gives us is an indication of how the UPC will approach the issues of undue burden and trial and error with respect to functional claims for antibody and related biologics. The US considers that the sheer amount of effort required to produce all the antibodies under the scope of a broad functional antibody claim leads to a lack of enablement. By contrast, the EPO is generally content with accepting that making new antibodies falling under a functional definition is entirely within the capabilities of the skilled person, and that it doesn't matter that it would take them a very long time.

At the EPO, broad functional antibody claims fall down for more specific reasons, such as post-published data showing that there is no clear correlation between, e.g. a claimed functional feature of a genus of antibodies and their claimed therapeutic effect (T 0709/23, IPKat). A broad functional antibody claim, e.g. defined by an epitope sequence, may also be undermined at the EPO if it can be shown that a skilled person would not be able to use standard techniques to find other antibodies falling under the scope of the claim, e.g. because of the lack of appropriate assays for screening antibodies for binding to a conformational epitope (T 0435/20, IPKat). However, successful sufficiency attacks against broad functional antibody cases at the EPO remain rare. Both the first instance decision from the Munich Central Division (IPKat) and now the UPC CoA decision in Amgen v Sanofi indicate that the UPC intends to follow the EPO's lead on the sufficiency standard for broad functional antibody inventions.

Inventive Step Analysis: Evaluating reasonable expectation of success versus a hope to succeed

At first instance, the patent fell down for inventive step, indicating that the UPC also intended to follow the EPO's strict approach to the inventive step of antibody claims. The question on appeal was whether the UPC CoA would follow the same hard line.

On inventive step, the CoA agreed with the lower court that a realistic starting point for inventive step was a paper (Lagace) disclosing that PCSK9 reduces LDLR levels and suggesting that inhibitors, including antibodies, could be explored for treatment. However, where the Central Division saw a clear path to the invention in view of this prior art, the Court of Appeal was not as convinced. The CoA focused on the scientific knowledge at the priority date. The CoA noted that, at the priority date in 2008, it was known that PCSK9 could function through two pathways: an intracellular pathway and an extracellular pathway. Antibodies, being large molecules, cannot enter the cell and thus can only target the extracellular pathway. The CoA thus reasoned that for a skilled person to have a reasonable expectation of success, they would have needed to know that blocking the extracellular pathway alone would be sufficient to achieve a therapeutic effect in vivo. The CoA found that the prior art, including Lagace, left the relative contribution of these pathways unresolved. Lagace itself stated, "we do not know which pathway predominates," and the Court noted that other contemporaries in the field shared this uncertainty.

Interestingly, the CoA also found that the mere fact that pharmaceutical companies were working on PCSK9 antibodies did not prove a reasonable expectation of success. For the CoA, this merely indicated that PCSK9 was an interesting target to explore with a "hope to succeed" (Headnote 22). For the CoA, the skilled person could not have reasonably predicted that an antibody approach would result in a therapeutically effective treatment, and the invention was therefore not obvious. The Court of Appeal therefore set aside the revocation decision and maintained the patent as granted.

The UPC’s "holistic" approach vs. the EPO’s "problem-solution" approach to inventive step

The key aspect of the UPC's approach to inventive step influencing the outcome of this case is summarised in Headnotes 19 and 20:

19. 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.

20. 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.

It is clear from the UPC's own summation of its approach that it intends to take a case-by-case and context specific approach to inventive step, focusing on the evidence presented. Whilst the UPC CoA did not follow the strict problem-solution approach to inventive step employed by the EPO, in favour of a more "holistic approach", it is not clear to this Kat that this amounts to any likelihood of significant divergence in outcomes in cases based on the same facts. Decisions from the Boards of Appeal in which antibody inventions have fallen down for inventive step were for reasons arguably entirely aligned with the UPC's framework as outlined in the Headnotes of Amgen v Sanofi, e.g. negative post-published data undermining the purported technical effect (T 2552/22), or a therapeutic effect found obvious in view of mechanistic data in the prior art (T 1505/23). On inventive step, at least, this Kat therefore sees no obvious divergence in the approaches of the UPC and EPO. The technical details of the case are generally what swings the decision in both arenas.

Final thoughts

For those wishing for harmonisation between EPO and the UPC, the decision of the UPC CoA in Amgen v Sanofi offers some clarity and reassurance. The UPC and the EPO are now clearly on one side of the line with respect to the sufficiency of broad scope antibody claims, with the US on the other.

On inventive step, much has already been made of the fact that the UPC has rejected a strict adherence to the EPO problem-solution approach in favour of a "holistic approach". However, for this Kat, this difference is probably of little practical significance. The questions central to the UPC's inventive step analysis in this case would have been the same whatever approach would have been taken. The focus of the UPC was on the skilled person's reasonable expectation of success. The EPO employs very similar reasoning and analysis for broad functional claims. One only has to compare the present case with that of the Board of Appeal in T 0136/24 (IPKat, interestingly a case with Sanofi as the Patentee). The Board of Appeal conclusion in T 0136/24 that a "hope to succeed" is not equivalent to a reasonable expectation of success, can be directly compared with Headnote 22 of the UPC decision. All of this is to be welcomed. However, the significance of this for IP strategy relating to biologics continues to be outweighed by the huge gulf between the US and European approach to antibody inventions.