The Munich Central Division revoked EP 3666797B across the UPC member states in which it was in force for lack of inventive step, and in doing so provided further insight into claim construction and the assessment of inventive step at the UPC. This decision is also the first in the field of antibodies.

The key takeaways are as follows:

1. Commitment to the one-year timeline for a first instance decision.
2. Claim interpretation considers the language of the claims, including technical function of features alone and as a whole, as well as the description and drawings.
3. The description may be considered as the patent’s “lexicon”, especially in the absence of an accepted meaning of a term in the art.
4. The concept of “same invention” within the meaning of Article 87 EPC (priority) is to be assessed narrowly according to G 2/98 from the EPO’s Enlarged Board of Appeal.
5. Inventive step is to be assessed from any “realistic” starting point.
6. An argument that another document is “closer” or “more realistic” is likely to fail.
7. Skilled person may be considered a “team” of relevant technical persons.
8. Arguments as to a lack of a reasonable expectation of success are likely to fail if there are no technical difficulties in taking “next steps” from the starting point and the skilled person would be motivated to do so.
9. Therapeutic antibody inventions in the UPC are likely to be assessed in a similar manner to the EPO; development of new antibodies for a known target is routine.

Background and technology

Sanofi’s Patent EP 3666797B 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
• reducing the risk of a recurrent cardiovascular event related to elevated serum cholesterol levels.

The monoclonal antibody or antigen-binding fragment thereof was defined as binding to the catalytic domain of a PCSK9 protein of the amino acid sequence of SEQ ID NO:1, and preventing or reducing the binding of PCSK9 to LDLR.

In essence, granted claim 1 was a second medical use claim where the antibodies being used to achieve the claimed technical effect were defined functionally.

The patent explains how PCSK9 is a serine protease, an enzyme that cleaves peptide bonds in proteins, involved in regulating the levels of the low density lipoprotein receptor (LDLR) protein. LDLR is a protein receptor expressed on the surface of liver cells that is important for removing low density lipoprotein cholesterol (LDL-C). Typically, LDLRs on the cell surface bind to LDL-C, transport LDL-C into the cell where it is broken down for the use by the body, and are then recycled to the cell where they can continue their role of transporting LDL-C from the bloodstream into the cell.

Hence, the aim of the patent was to provide the above-defined medical use, by targeting PCSK9 to regulate levels of LDLRs (and thereby LDL-C). This aim was explicitly highlighted by the Munich Central Division before construing claim 1.

Claim interpretation

The legal framework applied by the Munich Central Division for claim construction was that set out by the UPC Court of Appeal in NanoString v 10x Genomics (UPC_CoA_335/2023). This requires a consideration of how a person skilled in the art would understand the feature in view not only of the literal meaning of the claim wording, but with the description and drawings. The Munich Central Division also referenced the UPC Court of Appeal decision in VusionGroup v Hanshow (UPC_CoA_1/2024), to emphasise that a feature in a patent claim must be interpreted in light of the claim as a whole.

What this appears to mean in practice is that a feature should not be interpreted in isolation, but with a consideration of any technical relationship with other features in the claim, and the context of the feature in the description and any drawings.

In this case, the main feature interpreted by the Munich Central Division was “binds to the catalytic domain”.

The “catalytic domain” was not explicitly defined in EP 3666797B and there was no “commonly accepted state of the art definition”. After considering the wording of the claim, the explanation in the description, and the drawings, it was held that this meant “the region consisting of amino acid residues 123 to 419 of human PCSK9 (SEQ ID NO:1)”.

It was also noted that the product must be therapeutically effective in view of the “underlying problem”. This meant that the claim was not interpreted as covering “all antibodies capable of binding to the catalytic domain”, but those that allowed the claimed result to occur (preventing or reducing the binding of PCSK9 to LDLR). This interpretation relied extensively on the description.

The Munich Central Division also noted that: “Even if terms used in the patent deviate from general usage, it may therefore be that ultimately the meaning of the terms resulting from the patent specification is authoritative”.

The UPC divisions have not yet been presented with a situation where there is a significant difference in meaning between the claim and the description. The above statement and the reliance on the description in the substantive decisions issued so far by the various divisions and UPC Court of Appeal does, however, suggest that the description definition may be adopted in such a situation. In view of the pending referral to the Enlarged Board of Appeal in G 1/24 on claim interpretation, this is an area that European patent attorneys are monitoring closely.

Inventive step assessment

On inventive step, the Munich Central Division did not strictly follow the European Patent Office’s (EPO) problem-solution approach. Instead of first identifying the “closest prior art” it referred to NanoString v 10x Genomics (UPC_CoA_335/2023) and deemed that a “realistic” starting point was all that was needed. It was also noted that there can be several realistic starting points.

In view of this position, Amgen’s argument that another document (Graham) was “closer” and “more realistic” were not successful. Graham had been taken as the closest prior art during examination before the EPO.

Lagace described the biological role of PCSK9, including its function to regulate LDLR protein levels. The Munich Central Division summarised that the skilled person “would have realised that Lagace was interested in finding out more about the mechanism by which PCSK9 reduces the number of LDLRs”, because it was known that loss of PCSK9 expression resulted in lower plasma cholesterol levels in vivo. Hence, it was a “realistic” starting point.

Lagace also taught that the development of anti PCSK9 antibodies that block the LDLR:PCSK9 interaction “can be explored for the treatment of hypercholesterolemia”. From this teaching it was held that the skilled person would have pursued antibodies blocking the interaction as “a next step”, and, as there were no serious obstacles and only routine screening methods were required, it did not involve inventive skill to identify the claimed antibodies.

The Munich Central Division thus rejected Amgen’s arguments focused on PCSK9 not being a genetically validated target, and the skilled person not pursuing an antibody approach “at least not with a reasonable expectation of success”. The reasonable expectation of success argument appears to have failed because Amgen did not demonstrate that the skilled person would have had “serious doubts” that a therapeutic antibody could be developed. The term “serious” was quantified as “doubts that were of such a nature that these would have dissuaded the skilled person from pursuing an antibody approach to block the interaction…as suggested by Lagace”.

The granted claims were found to lack an inventive step. The same conclusion applied to all seventeen auxiliary requests.

Final comment

There are pending EPO opposition proceedings in which Sanofi is one of the opponents. Unsurprisingly, the representative for Sanofi filed a copy of the UPC decision the day it was issued and highlighted that the Munich Central Division had found the patent to lack an inventive step over Lagace. Lagace was presented as closest prior art in its opposition. The parties have not yet been summoned to oral proceedings. When they are, it will be interesting to see how the Opposition Division deals with the UPC decision in its preliminary opinion, and whether it seeks to align itself or take an independent (perhaps even different) approach.

We expect the EPO to align itself with the Munich Central Division, but perhaps with the application of a more conventional problem-solution approach to inventive step. This may be seen as a modified version of the EPO’s problem-solution approach, thereby allowing each jurisdiction to come to the same conclusion if by slightly different means.

Amgen have appealed the decision since in an order from the Munich Local Division on 29 July 2024, it is noted that the parties agreed to stay the infringement proceedings (also involving Regeneron) pending the outcome of the appeal against the revocation decision. We will monitor the developments of this ongoing dispute.

Case details at a glance

Decision level: Düsseldorf Local Division
Case: UPC_CFI_7/2023
Parties: Franz Kaldewei GmbH & Co KG v Bette GmbH & Co KG
Date: 03 July 2024
Decision: dycip.com/franz-kaldewei-bette-jul24

Decision level: Paris Local Division
Case: UPC_CFI_230/2023
Parties: DexCom, Inc v Abbott Laboratories et al
Date: 04 July 2024
Decision: dycip.com/dexcom-abbott-jul24

Decision level: Munich Central Division
Case: UPC_CFI_1/2023
Parties: Sanofi-Aventis Deutschland GmbH et al v Amgen Inc.
Date: 16 July 2024
Decision: dycip.com/sanofi-amgen-jul24