Sanofi v Amgen: UPC revokes Amgen’s antibody patent in its first revocation order

The first revocation order has now been issued by the Central Division of the Unified Patent Court (UPC), in the litigation between Sanofi and Regeneron (the Claimants) v Amgen (the Defendants) (UPC_CFI_1/2023 – Sanofi v Amgen).

This is the first decision of its kind, which becomes effective across all 17 UPC Member States. It remains to be seen if Amgen will appeal the decision. Importantly, then, this illustrates the territorially wide power that UPC decisions can have across Europe, and, given that the decision issued a little over 12 months after the UPC first opened for business on 1 June 2023 (with the Oral Hearing being held on 4 June 2024), it also shows just how quickly cases can progress before the UPC.

The UPC for this case consisted of three judges, including a German presiding judge, a Dutch legally qualified judge, and a Danish technically qualified judge, and the decision helps to establish the UPC’s (at least initial) position on the patentability of therapeutic antibody inventions in Europe. In short, the judges held that the patent was invalid for lack of inventive step over just one prior art document, largely following the EPO’s approach to assessing the patentability of antibodies, where the isolation of a new antibody specific for a known target antigen is considered to be routine to the skilled person. Contrast this with the US, where the US Supreme Court held that Amgen’s corresponding US patents lacked enablement because they took the view that it would require more than routine efforts to work the invention over the whole claim scope.

Amgen’s Patent

The case concerns a revocation action brought against one of Amgen’s patents, EP3,666,797 B1, relating to antibodies that bind to proprotein convertase subtilisin kexin type 9 (PCSK9), and their use for treating conditions exacerbated by high cholesterol levels. The antibodies block the binding of PCSK9 to receptor protein LDLR, thereby increasing the levels of LDLR which can remove low density lipoprotein cholesterol (LDL-C) from the blood.

Claim 1 of the patent, as granted, is 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.”

As such, claim 1 is a second medical use claim, directed to the therapeutic use of an antibody that is defined only by its function, and not by its structure.

Claim Interpretation

In order to reach its decision, the UPC judges first had to construe the various features in claim 1. The judges stated:

“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 drawings. From the function of the individual features in the context of the patent claim as a whole, it must be deduced which technical function these features actually have individually and as a whole. The patent description may represent a patent’s own lexicon”. [Headnote 1].

Accordingly, the Central Division considered that the interpretation of a patent claim does not depend solely on the strict, literal meaning of the wording used, but rather, that the description and drawings must always be used as explanatory aids for the interpretation of the patent claim. This means, then, that although we still await the decision on the pending referral to the EPO’s Enlarged Board of Appeal (G1/24) to consider what weight should be given to a patent’s description when considering claim scope, in this decision, the UPC took the view that the description is clearly very important in construing how to interpret claim scope.

Applying these principles to the case at hand, the Court examined the claim’s functional feature ”binds to the catalytic domain of a PCSK9 protein”, in view of the description and the claim as a whole. In relation to the term “binds to”, the Court considered that claim 1 is not limited to antibodies that bind exclusively to amino acid residues within the catalytic domain. As such, antibodies that bind to the catalytic domain and also to other domains of PCSK9 fulfil the feature ”binds to the catalytic domain of a PCSK9 protein”.

The Court also considered the other functional limitation of the claim, i.e., the therapeutic effect of the antibodies (cholesterol reduction). In view of the teaching of the patent as a whole, the Court concluded that a (very) small cholesterol-lowering effect caused by the claimed antibodies can be “therapeutically effective” in the sense of the claimed treatments.

Ultimately, the Court concluded that the functional language of the claim should not be construed as covering “all antibodies that may conceivably bind to the catalytic domain”. However, the claims were understood as not being limited to just the exemplary antibodies described in the description.

Inventive Step

Next, the Court considered whether the claimed subject matter involves an inventive step according to Article 56 EPC. In doing so, interestingly, they decided not to follow the EPO’s well-established problem-solution approach that is normally employed to assess non-obviousness in Europe, which requires a first step of identifying the “closest prior art”. Instead, the UPC stated:

“The assessment of inventive step starts from a realistic starting point in the prior art. There can be several realistic starting points. It is not necessary to identify the “most promising” starting point.” [Headnote 3]

As such, the judges said that it was enough to identify a “realistic starting point”, defined as one which would have been of interest to a skilled person who, at the priority date of the patent, was seeking to develop a similar product or method to that disclosed in the prior art which thus has a similar underlying problem as the claimed invention.

Lagace et al. 2006 (“Lagace”)was taken as the realistic starting point for the assessment of inventive step. The Court found that whilst Lagace does not disclose any antibodies that bind to the catalytic domain of PCSK9 and block the interaction between PCSK9 and LDLR, it does disclose that “the development of anti PCSK9 antibodies that block the LDLR:PCSK9 interaction can be explored for the treatment of hypercholesterolemia”.

Therefore, the Court concluded that there was a strong incentive at the priority date for the skilled person to develop antibodies that block the interaction of PCSK9 with the LDLR, in order to reduce LDL levels and treat hypercholesterolemia. Furthermore, the Court stated that generating and selecting such antibodies was a “matter of routine” for the skilled person, and that they would have had a reasonable chance of success in obtaining the antibodies defined in the claims without involving an inventive step.

In addition, it is important to note that claim 1 is drawn to a therapeutic use of a functionally defined antibody, and not a structurally defined one, and that the Court considered that there is “no apparent causal technical connection between the feature “binds to the catalytic domain” and the reduction of the binding of PCSK9/LDLR and, ultimately, the therapeutic effect claimed”. As such, the functional feature “binds to the catalytic domain” could not be considered to contribute to an inventive step.

In conclusion, therefore, the Court found that the skilled person would have been motivated to develop therapeutic antibodies against PCSK9 and that they would have arrived at the claimed antibodies with a reasonable chance of success without an “undue burden”. Therefore, the Court revoked the patent in its entirety due to lack of an inventive step, a decision which is effective for all 17 UPC contracting states in which the patent is in force.

Conclusions

This landmark decision has shown that the UPC is prepared to deviate somewhat from the EPO’s current position on at least claim interpretation and, to some extent, assessing inventive step. However, reassuringly, the UPC’s overall approach to the patentability of antibodies is still very similar to that of the EPO, where it is considered that the development of new antibodies for a known target is considered routine (see EPO Guidelines for Examination, G-II, 6.2).

Furthermore, this decision confirms that the European approach to antibody inventions still significantly contrasts to the approach that is taken in the US. In Europe, the claimed invention in Amgen’s European patent was found to lack an inventive step because the development of new antibodies for a known target is considered routine unless there are any technical challenges that may be associated with targeting that specific antigen. In contrast, however, the US Supreme Court previously held that Amgen’s corresponding US patents (US 8829165 and US 8859741) lacked enablement, because, in their view, it was considered that working the invention over the whole scope of the claim requires more than routine efforts. Thus, although the European and US approaches to antibody inventions are currently diametrically opposed, in this case, they have still reached the same conclusion that the corresponding patents are invalid, albeit for quite different reasons.