Sanofi/Regeneron succeed against Amgen in first revocation decision issued by a Central Division of the UPC

On 16 July 2024, the Munich Central Division published its decision in an action for revocation by a Sanofi group of companies (Sanofi) of EP 3 666 797 B1 (EP 797), held by Amgen, Inc. (Amgen) (UPC_1/2023). Amgen had brought an infringement action against Sanofi and Regeneron Pharmaceuticals Inc. (Regeneron) relating to the same patent in the Munich Local Division of the UPC (UPC_14/2023). Regeneron counterclaimed for revocation, which was referred to the Central Division with the agreement of the parties. Following referral, the Central Division ordered that the revocation action and counterclaim be dealt with jointly.

EP 797 was granted on 17 May 2023. Alongside the UPC challenge, the patent has also been opposed at the EPO by Sanofi-Aventis Deutschland (on 10 November 2023) and Regeneron Pharmaceuticals Inc. (on 19 February 2024).

EP 797 relates to antibodies (or antibody fragments) that bind to proprotein convertase subtilisin kexin type 9 (PCKS9) and methods of using and making them.

Claim 1 of EP 797 as granted claimed “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.”

Sanofi and Regeneron argued before the Central Division that EP 797 should be revoked for adding subject-matter beyond the content of the application as filed, lack of sufficiency, lack of novelty and/or lack of inventive step. Amgen put forward various defences, which included an application to amend EP 797.

Claim interpretation 

The parties differed in their approach to claim construction and so the Central Division considered it necessary to interpret claim 1. Having set out the legal framework on interpretation of claims laid down in 10x Genomics and Harvard v Nanostring (UPC_CoA_335/2023) (10x Genomics v Nanostring), the Central Division accepted the position of Amgen that claim 1 is not limited to antibodies that bind exclusively (or even predominantly) to an epitope within the catalytic domain. Instead, the claim covers antibodies that bind to the catalytic domain and also to other domains of PCSK9, i.e. the pro or V-domains.

Novelty and Priority

The claimants’ challenge to the novelty of EP 797 relied on two documents that could only form part of the state of the art if EP 797 was not entitled to its claimed priority date. The Central Division rejected the claimants’ arguments on priority, applying the test set out in EPO EBA Case no. G 2/98, that a claimed invention will only be considered the “same invention” for the purpose of claiming priority 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” (emphasis added). This reflects the EPO’s “gold standard” approach that we have seen applied in other areas of validity, including added matter by the Hague Local Division in Abbott v Sibio (UPC_CFI_131/2024) and novelty in DexCom, Inc. v Abbott Laboratories (UPC_CFI_230/2023).

As the priority challenge failed, it followed that the claimants’ novelty challenge also failed.

Inventive Step 

Reflecting the approach taken in 10x Genomics v Nanostring, the Central Division took a more holistic approach to assessing inventive step than the strict EPO-style problem-solution approach. The Central Division identified the relevant test as follows:

(i) Identify a realistic starting point; and

(ii) Compare the claimed subject matter and prior art to determine whether it would be obvious for the skilled person to, starting from a realistic prior art disclosure, in view of the underlying problem, arrive at the claimed solution.

The Central Division considered that a starting point will be considered realistic if its teaching would have been of interest to a skilled person who, at the priority date of the patent in issue, was seeking to develop a similar product or method to that disclosed in the prior art and therefore had a similar underlying problem as the claimed invention.

Further, a claimed solution is obvious if, starting from the prior art, the skilled person would be motivated to consider the claimed solution and to implement it as a next step in developing the prior art. The Central Division set out the principle that a technical effect or advantage of a feature of the claimed subject matter may be indicative of inventive step, whereas a feature that results from an arbitrary selection from several possibilities will generally not be. The Central Division also emphasised that hindsight must be avoided.

The Central Division ultimately concluded that EP 797 was invalid for lack of inventive step over the prior art identified by the claimants as the starting point for the assessment, namely Lagace et al. 2006 (Lagace). Amgen sought to argue that a later citation, Graham 2007 was a closer and more realistic starting point. However, it was not disputed that Lagace was a realistic starting point, which the Central Division agreed with. Having concluded that Lagace was a realistic starting point, the Central Division did not consider it necessary to assess whether any other starting point would be “more promising”. The Central Division also noted that there “can be several realistic starting points… [it is] not necessary to identify the “most promising” starting point”.

Lagace included a statement suggesting that “the development of antibodies to block [PCSK9] interaction with the LDLR or inhibitors to block its action in plasma, can be explored for the treatment of hypercholesterolemia”. However, it did not disclose any antibodies that bind to the catalytic domain of PCSK9 and block the interaction between PCSK9 and LDLR which are actually used for the treatment of hypercholesterolemia. The Central Division indicated that these differences must be considered for the assessment of obviousness.

Applying the tests outlined above, the Central Division concluded that using Lagace as a starting point, the skilled person would pursue the route of developing antibodies as suggested in Lagace, thereby arriving at antibodies as defined in the claims of EP 797 without any inventive skill. In reaching its decision, the Central Division considered it relevant that, at the priority date, there was significant commercial interest in PCSK9 as a target for the treatment of hypercholesterolemia; a significant number of pharmaceutical companies were pursuing options to target PCSK9 at the time. Further, the Central Division disregarded the uncertainties Amgen sought to argue would have stood in the way of the skilled person’s arrival at the antibodies claimed in PCSK9, noting that none of these concerns were clearly expressed in the cited prior art. The same reasoning applied to Amgen’s auxiliary requests.

Decision

The Central Division therefore ordered that EP 797 be revoked for lack of inventive step in all of the UPC Contracting States in which it was in force (as per the claimants’ request). Amgen was ordered to pay €1.375 million for the claimants’ legal costs.

Comment

This decision is notable not just as the first successful revocation action from a central division in the UPC, but also because it provides further insight into the principles being applied when assessing patent validity. .

Initial decisions have shown that, perhaps unsurprisingly, the UPC divisions appear to be guided by the EPO-style approach when assessing validity. This is particularly true in respect of added matter, priority and novelty, where the UPC divisions have so far adopted the EPO’s “gold standard” approach.

However, the decisions of the Paris Local Division in DexCom v Abbott (UPC_CFI_230/2023) and of the Düsseldorf Local Division in Franz Kaldewei v Bette (UPC_CFI_7/2023) indicate that, following 10x Genomics v Nanostring, that is not necessarily the case for inventive step; in those cases the UPC divisions applied an EPO-style approach when assessing inventive step, including the determination of an objective technical problem to be solved, but did not adhere to a strict problem-and-solution approach. Further, it now seems that the UPC divisions are willing to adopt new approaches and tests, such as the more holistic approach to assessing inventive step applied by the Munich Central Division in Sanofi/Regeneron v Amgen.