SPCs: first applications in France of CJEU Royalty Pharma test

Monoclonal antibodies are biologic drugs that act like the human antibodies in the human immune system. They are used in immunotherapy to bind to specific cells or proteins, for instance to inhibit their activity.

When a new monoclonal antibody therapy is discovered, it is typically first protected by a patent family covering a function rather than a specific antibody – for instance, the use of a monoclonal antibody to inhibit a specific protein found to play a role in protecting cancer cells from the body's immune system attacks. When, following subsequent research, specific monoclonal antibodies performing such function are isolated, later patents are filed to disclose and protect their structure.

Jules Fabre and Marina Jonon of Pinsent Masons, the law firm behind Out-Law, were commenting after the Paris Court of Appeal ruled that applications for SPCs on the monoclonal antibody products nivolumab, pembrolizumab and osimertinib should be rejected as the products were not specifically identifiable from the functional definition in the basic patents relied on for the purpose of these applications.

The rulings in the three cases are the first in France, and among the first in Europe, to apply case law established by the Court of Justice of the EU (CJEU) in the case of Royalty Pharma, which last year clarified the legal test for determining eligibility for SPCs for product covered by a functional definition in the underlying patent.

SPCs serve to extend the life of a patent by up to a maximum of five years for products which are authorised under the relevant regulatory framework in the field of medicinal and plant products.

Under the EU SPC Regulation, SPCs can only be granted if, in the EU country in which the application is submitted, the product is "protected by a basic patent in force" and market authorisation has been issued to place that product on the market as a medicinal product, so long as that authorisation is the first of its kind and an SPC has not already been issued for the product.

In the Royalty Pharma case last year, the CJEU assessed what criteria need to be satisfied for a product to be considered as 'protected' by a basic patent, under Article 3(a) of the SPC Regulation, when the product is not expressly disclosed in the basic patent but is covered by a functional, rather than structural, definition in the basic patent.

The CJEU built on existing case law in this area which had been developed in previous cases and more recently in the case of Teva v Gilead, in which Pinsent Masons acted for Teva. In that case, the CJEU established a two-limb test for defining what must be protected by the basic patent in order to obtain an SPC in relation to combination products.

It said that the combination of the active ingredients of a product must necessarily, in the light of the description and drawings of that patent, fall under the invention covered by that patent, and that each of those active ingredients must be specifically identifiable, in the light of all the information disclosed by that patent.

The assessment of whether that criteria is met must be carried out through the eyes of a "person skilled in the art and on the basis of the prior art at the filing date or priority date of the basic patent". The combination of active ingredients does not need to be expressly mentioned in the claims of the basic patent if those claims relate necessarily and specifically to that combination, it held.

In the Royalty Pharma case, the CJEU confirmed that the two limb test also applies to single products covered by a functional definition in the underlying patent.

The CJEU said that a product corresponding to a general functional definition used in the basic patent and which necessarily falls under the invention covered by that patent but is not otherwise indicated in individualised form as a specific embodiment, must be specifically identifiable by a skilled person to be considered to be 'protected' by that basic patent.

Adding to the Teva v Gilead test, the CJEU also said that a product that was developed after the filing of the basic patent following "an independent inventive step" cannot be considered as protected by the basic patent even if it falls under a functional definition in the patent claims. However, the CJEU did not give guidance on what should be considered an "independent" inventive step, a concept that did not exist in patent and SPC law. Therefore, businesses were eagerly awaiting interpretation on this point from patent offices and national courts given the important implications on eligibility to SPC protection.

In two judgments handed down on 19 January 2021, the Paris Court of Appeal rejected SPCs for nivolumab, which is sold under the brand name Opdivo, and pembrolizumab, sold under the brand name Keytruda.Both products are monoclonal antibodies. Opdivo and Keytruda are marketed by Bristol-Myers Squibb and MSD, respectively, and are among the top five best-selling drugs globally.

In these cases, Ono Pharmaceutical and Nobel laureate professor Dr. Tasuku Honjo bid to obtain SPCs in France for the two monoclonal antibodies on the basis of a basic patent relating to the use of a specific  antibody known as anti-PD1 in an immunotherapy treatment for cancer. A.

The French National Institute for Industrial Property (INPI) had previously rejected both SPC applications – decisions Ono and professor Honjo appealed. In its judgments, the Paris Court of Appeal said that the products fell within the functional definition of the patent claims and were "implicitly and necessarily" covered by the basic patent. This meant they satisfied the  first limb of the CJEU test from the Teva v Gilead case. However, it considered that the products were not "specifically identifiable" by the person skilled in the art – as required under the second limb of the test – from the basic patent, as their identification could not be achieved with routine steps but would require an independent inventive step.

The court noted in this respect that the research and development work that was necessary to undertake beyond what was described in the patent to characterise, prepare, obtain and produce the monoclonal antibodies would involve particularly complex steps and significant and costly resources in terms equipment, time and labour.

In the case of nivolumab and pembrolizumab, patents were filed for that disclosed the specific sequence and structure of the products three and five years respectively after the initial basic patent that claimed the inhibiting function of anti-PD1 antibodies had been applied for. The Paris Court of Appeal considered that lag in time before the specific patents were filed for the two products was a reflection of the complexity of the additional research needed to identify the relevant antibodies for each product from the possibilities provided for under the basic patent.

In light of its findings, the court confirmed the INPI's earlier decisions to reject both SPC applications. The court also noted that SPCs had already been granted in relation to both nivolumab and pembrolizumab, on the basis of patents disclosing each antibody specifically, and so considered that the objective of the SPC Regulation to compensate for the delay and investments involved in obtaining regulatory approval in the field of pharmaceuticals will be achieved for both products.

On 9 February 2021, the Paris Court of Appeal handed down a third judgement in which it applied the CJEU's concept of "independent inventive step". The case related to an SPC application for osimertinib, a product which is used to treat lung cancer and is marketed by AstraZeneca under the brand name Tagrisso.

The SPC application had been jointly filed by Wyeth and the General Hospital Corporation (GHC) on the basis of a basic patent covering a method for treating cancer which was resistant to one or both of gefinitib erlotinib – two other products that have been developed to treat certain types of cancer. The basic patent concerns the administration of a special type of protein – an irreversible epidermal growth factor receptor (EGFR) – that acts as an inhibitor to the natural immune system response that can be detrimental to treatment. The claims of the basic patent did not disclose osimertinib explicitly.

The INPI rejected the SPC application, considering that the osimertinib was not 'protected' by the basic patent within the meaning of Article 3(a) of the SPC Regulation. Wyeth and GHC appealed.

The Paris Court of Appeal accepted that osimertinib was an EGFR receptor inhibitor and said that it was "implicitly and necessarily" covered by the functional definition of the basic patent. However, relying on the CJEU decision in the Royalty Pharma case, the Paris Court of Appeal found that osimertinib was not "specifically identifiable" by the person skilled in the art from the basic patent as its identification could not be achieved with just routine steps, but would have required an ‘independent’ inventive step.

In this respect, the court noted that several years of research had been necessary to "precisely and specifically" identify osimertinib as an active ingredient, that AstraZeneca’s patent disclosing the structure of osimertinib was filed six years after the basic patent and that studies published by the applicants years after the basic patent in relation to potential candidates under evaluation did not even mention osimertinib.

In addition, the court was not convinced by the argument raised by the applicants that the disclosure from the basic patent would have formed the groundwork for identifying osimertinib. The applicants had highlighted that the disclosure had been referred to as relevant prior art in the description in the later patent on osimertinib and other publications from the inventor. However, the court said that whilst the disclosure in the basic patent did contribute to the research on EGFR inhibitors in general this did not mean that an independent inventive step was not required to identify osimertinib specifically, and that the contribution of the disclosure in the basic patent was one among several others.

As a result, the Paris Court of Appeal confirmed the INPI's decision to reject the SPC application.

Jules Fabre of Pinsent Masons said: "In view of these recent judgments, it seems that it will be difficult for SPC applicants in France to meet the CJEU's Royalty Pharma test in relation to monoclonal antibodies when relying on a basic patent which claims an inhibiting function but does not contain additional disclosure in relation to the relevant antibody."