Easter always brings back chocolaty memories. The question as a child growing up in the Northeastern part of France on Easter morning was whether eggs had been brought by the Easter bunny. And the question as a child also growing up in the Southeastern part of France was whether eggs had been brought by the Easter bells.
It has been a while since the Easter bunny and the Easter bells stopped feeding me with chocolate. But this year there was an even better surprise on Sunday morning, in the form of an SPC-related guest post by Lionel Vial. And as all readers will probably acknowledge, SPCs are a delicacy of their own.
Here is to Lionel.
The case discussed on this Easter day relates to a ruling of the Paris Cour d’appel dated January 20, 2017 which upheld a decision of the French patent and trademark office (INPI) to reject an application for a supplementary protection certificate (SPC) for a biological medicinal product.
French SPC application No. 11C0054 was filed on December 14, 2011 by Laboratoire Français du Fractionnement et des Biotechnologies (hereafter LFB), a French company specializing in medicinal products purified from human blood. The SPC application was based on French patent No. 2722992 filed on July 28, 1994, which claimed a method for the manufacture of a C1-esterase inhibitor concentrate (claim 1), as well as the concentrate obtained by the method (claim 11).
The SPC application was further based on marketing authorization (MA) No. EU/1/11/688/001 for Cinryze® comprising “C1 inhibitor, human (INN)” as active ingredient.
For those whose curiosity goes beyond patent law, C1 is one of the proteins forming the complement system, which itself is part of the innate (i.e. non-adaptive) immune system. The C1 inhibitor is a natural protein, found in blood, the role of which is to regulate the activation of the complement system. The C1 inhibitor is especially useful for individuals suffering from a rare autosomal dominant disease, caused by a deficiency of functional endogenous C1 inhibitor, which manifests itself in the form of angioedema attacks.
The SPC application was rejected on December 22, 2014 by the INPI for not complying with Article 3(d) of Regulation (EC) No. 469/2009 (hereafter the SPC regulation), i.e. the MA for Cinrize® was considered not to be the first authorization to place the product on the market as a medicinal product.
This was because a prior MA had been issued on June 28, 1999 for Esterasine comprising “human C1 esterase inhibitor” as active ingredient.
LFB lodged an appeal against the decision of the INPI before the Paris Cour d’appel and essentially argued that the human C1 inhibitors of Cinrize® and Esterasine were in fact two different products.
The precise arguments used by LFB are not very clearly summarized in the decision.
But it appears that LFB stressed that the way biological medicinal products, such as Cinrize®, are manufactured has an impact on their molecular structure, which, in the present case, was evidenced by a half-life of 56 hours for Cinrize® vs. 30 hours for Esterasine.
This did not convince the Cour d’appel which considered that:
The regulation relating to SPCs does not provide for exceptions to the definitions of a “product” and a first MA for biological medicinal products or blood products which would allow defining them as a function of their methods of manufacture or under their commercial names; it is therefore irrelevant that the SPC application is based on an MA for the “Cinryze” drug since the product protected by the basic patent is “the C1 inhibitor, human”; [besides] if LFB, after having initially claimed the latter, has amended the application by claiming “the C1 esterase inhibitor of the Cinryze drug”, this limitation made after the objections of the INPI cannot be effective since either the patent or the MA only relate to the “C1 inhibitor” as active ingredient of the Cinryze drug.
To put it more clearly, the Cour d’appel took a very formal approach of Article 3(d) of the SPC regulation and simply considered that, if the names of the active ingredients mentioned in two different MAs are the same, then both MAs in fact relate to the same product, without further consideration as to the true physicochemical identity between the two products, as in the case of biological medicinal products obtained by different methods of manufacture.
LFB also argued that, in the assessment report of the European Medicines Agency (EMA) which led to the MA, the purified and concentrated C1 INH (i.e. C1 inhibitor) after pasteurization and nanofiltration is considered as the active substance.
The Cour d’appel responded that
the subject matter of this report was a marketing authorization application for Cinryse, so that, if [the report] specifies what its active ingredient is, it does not conclude that it would be a new product, the novelty of the medicinal product being different from that of its active ingredient; accordingly this does not contradict the decision of the INPI.
Moreover, the Cour d’appel noted that this latter argument was not submitted to the INPI which, therefore, could not do otherwise than decide that the MA for the drug Cinryze was not the first one for the active ingredient which is the “C1 inhibitor, human”.
It is to be noted that the latter argument was however decisive in overcoming the objection of the Dutch patent office based on Article 3(d) of the SPC regulation for the corresponding SPC application in that country (NL SPC application No. 300510), thereby securing the grant of an SPC.
It is therefore tempting to imagine that the fate of the French SPC application could have been changed for the best had the attention of the INPI examiner been drawn to the definition of the active substance in the assessment report of the EMA.
As a final note, this case reminds us of the ruling of the Paris Cour d’appel of April 12, 2016 which upheld the decision of the INPI to reject SPC application No. 08C0003 covering Cervarix®(GlaxoSmithKline Biologicals) which was discussed here.
In that case also the Cour d’appel refused to take into account the impact of the manufacturing process of biological products (production in yeast cells vs. insect cells) on their structure, sticking to the definition of the product given in the MA.
One can wonder if this literal approach, which has the advantage of simplifying examination of SPC applications, is in keeping with the fundamental objective of the SPC regulation which is to make up for the insufficiency of the period of effective protection of a medicinal product under a patent to cover the investment put into pharmaceutical research as recalled by the CJEU in C‑130/11 (Neurim).
Indeed, in the present case, it appears from the assessment report of the EMA that new clinical data was produced for the C1 inhibitor of Cynrize® in support of the MA application. This is probably because the C1 inhibitor of Cynrize® is a biological product the structure of which depends on the manufacturing process, thereby making it impossible to rely on clinical data obtained with previous C1 inhibitors.
It is generally considered that clinical trials amount for the larger part of investment in drug development. It could therefore be considered that the active ingredient of Cynrize® is a new product the development of which necessitated investment entitling it to SPC protection.
As such, when assessing conformity with Article 3(d) of the SPC regulation, perhaps the necessity to generate specific clinical data in order to obtain an MA for a biological product should be the primary criterion for determining if an MA is the first one to place the biological product on the market, rather than simply determining if the name of the active ingredient is the same one as that of a prior MA.
Thank you Lionel. Easter being about resurrection even more than about chocolate eggs, it remains to be seen whether this SPC application may come back to life on cassation appeal.
CASE REFERENCE: Cour d’appel de Paris, pôle 5 chambre 2, January 20, 2017, SA Laboratoire Français du Fractionnement et des Biotechnologies v. Directeur général de l’INPI, RG No. 16/08814.