A French revolution

You may have heard that French revolutions have a reputation for violence. But things do not always have to be that way.

Case in point: a groundbreaking SPC ruling recently issued by the Paris Cour d’appel. Contrary to what you would expect, heads did not roll. Quite the opposite in fact: the revolution is precisely that the SPC at stake survived unscathed. Lionel Vial reports.

This is it. It has happened. The Paris Cour d’appel has finally reversed a decision of the French PTO (INPI) to refuse an SPC.

Indeed, as noted here, since we began discussing French SPC case law on this blog in 2016, the Paris Cour d’appel has upheld 100% of the 11 SPC refusals by the INPI that we have commented on.

What prompted the Cour d’appel to change its habit? Avelumab.

Avelumab is an anti-PD-L1 monoclonal antibody. It is the active ingredient of Bavencio® (Pfizer), which is indicated in the treatment of cancers.

Anti-PD-L1 antibodies, like anti-PD-1 antibodies, disrupt the PD-1/PD-L1 interaction in vivo, which accounts for their biological effects.

On November 17, 2017, the Dana-Farber Cancer Institute filed an application for an SPC (FR17C1046) based on European patent EP 1210424 (hereafter EP’424), filed on August 23, 2000, and on marketing authorisation (MA) EU/1/17/1214 for avelumab granted to Merck Europe B.V. on September 20, 2017.

Interestingly, the subject-matter of EP’424 essentially relates to PD-L1, which is claimed as an isolated polypeptide (in claim 12). EP’424 also generally claims “an antibody which selectively binds to a polypeptide of claim 12” (claim 17) and “an antibody which selectively binds to a polypeptide of SEQ ID NO: 2 or 4 [i.e. PD-L1]” (claim 27), but does not claim avelumab in itself. Indeed, avelumab is claimed in itself in a later patent, EP 2785375, filed on November 21, 2012 by Merck Patent GmbH, which forms the basis of SPC application FR20C1068.

On February 3, 2021, the INPI refused the SPC pursuant to Article 3(a) of Regulation (EC) No 469/2009 (hereafter the SPC regulation). Essentially applying the Royalty Pharma judgment of the Court of Justice of the European Union (CJEU) in case C-650/17, the INPI considered that while avelumab was implicitly and necessarily covered by the functional definition used in claims 17 and 27 of the basic patent, avelumab is nonetheless not specifically identifiable from the patent, avelumab having been developed after the filing date of the basic patent following an independent inventive step.

A very similar case was submitted to the Cour d’appel 2 years ago, leading to a decision on January 19, 2021, which we commented on here.

As a brief reminder, the Cour d’appel then sustained the decision of the INPI to reject an SPC application for nivolumab, an anti-PD-1 monoclonal antibody. The Cour d’appel considered that while nivolumab was implicitly and necessarily within the scope of the invention covered by the basic patent, the preparation of monoclonal antibodies required more than routine operations; furthermore, three years after the basic patent was filed were necessary to file a patent specifically relating to nivolumab, which was a sound indication that an independent inventive step was needed from the basic patent to arrive at nivolumab.

It is therefore quite a surprise that in the present case the Cour d’appel decided not to side with the INPI.

What seems to have been key in the new decision of the Cour d’appel was to take into account the criteria for inventive step which result from the European patent convention (EPC), as well as from the Guidelines and case law of the European patent office (EPO), in order to assess the “independent inventive step” criterion of Royalty Pharma.

The Cour d’appel thus considered that:

[…] The methods for generating and identifying an antibody directed against a given antigen are routine techniques for the person skilled in the art at the priority date; as a consequence, when the targeted antigen is already known, the discovery of an antibody binding to this antibody does not involve an inventive step.

Besides, the Cour d’appel did acknowledge that European patent EP 2785375, filed 11 years after the filing date of EP’424, was granted for avelumab but noted that the Examining division had first considered avelumab as lacking an inventive step and that if an inventive step was finally recognized by the EPO, it was due to the inter-species cross-reactivity of avelumab, and not for its capacity to bind to PD-L1.

Accordingly, the Cour d’appel went on to conclude:

It can be deduced from these elements, on the basis of the general knowledge of the person skilled in the art and from the state of the art at the priority date of patent EP464 that the human monoclonal antibody avelumab was specifically identifiable by the person skilled in the art in the light of the teachings of said patent, by known and well mastered routine experiments, which may be long and fastidious, but do not involve an independent inventive step.

The Cour d’appel admittedly also took into consideration the fact that the invention forming the subject-matter of EP’424 was a breakthrough invention which led to the marketing of several antibodies, such as avelumab, having a decisive public health impact in the fight against cancer.

How could the difference in outcome with the earlier case regarding the anti-PD-1 nivolumab then be explained, as the basic patent also contained guidance for manufacturing anti-PD-1 antibodies in this earlier case? Certainly not by the composition of the Cour d’appel, which was identical to the composition in the present case.

One possible explanation would be that, although the invention forming the subject-matter of the basic patent originated from the work of Tasuku Honjo, who won the Nobel prize for the discovery of PD-1, it was less of a breakthrough invention, as the basic patent neither claimed PD-1 (which was discovered several years before its filing) nor anti-PD-1 antibodies in general, and was indeed filed after EP’424. Besides, the SPC in that earlier case was also found by the Cour d’appel not to comply with Article 3(c) of the SPC regulation, which made the assessment of the compliance with Article 3(a) less crucial.

Whatever the reason, the present judgment is in our opinion a landmark decision which could be seen as lowering the bar which had been set by the Medeva (C-322/10) and Eli Lilly (C-493/12) case law to pass the requirements of Article 3(a) of the SPC regulation for monoclonal antibodies in France.

Last year, Renaud promised, perhaps a little too boldly, to do something special on this blog next time an SPC refusal would be overturned on appeal. I therefore leave it to him to surprise you!

What can I say, I should know better than to make reckless promises, especially when SPC law is involved. But I am not one to balk – and so, a surprise it is…

The surprise.

CASE REFERENCE: Cour d’appel de Paris, pôle 5 chambre 1, May 25, 2022, Dana-Farber Cancer Institute Inc. v. INPI, RG No.21/08514.