A risky launch at risk

Launching at risk is not a business for those who have a weak stomach.

Once a generic drug company has decided that it will go on the market despite the existence of an IP threat – e.g. because they have determined that the IP right at stake is probably invalid or unenforceable – then anything can happen, and it may happen really fast.

Today’s decision illustrates the risks of a launch at risk.

GD Searle LLC owns European patent No. EP 0810209 filed on August 24, 1993. The patent is directed to a family of antiretroviral drugs, more precisely protease inhibitors, useful for the treatment of HIV infection.

On May 9, 2008, Searle obtained a Supplementary Protection Certificate (SPC) from the French patent office (INPI), under No. FR 07C0034. This SPC is based on the EP’209 patent and relates to “darunavir or one of its pharmaceutically acceptable salts, esters or precursors“.

An exclusive license to the SPC was granted to Janssen Sciences Ireland Unlimited Company and then a sub-license was granted to its French affiliate Janssen-Cilag SAS. Janssen (Johnson & Johnson group) markets a drug known as Prezista®, the active compound of which is darunavir.

SAS Sandoz is a French affiliate of the Sandoz group (affiliated to Novartis). As readers have probably already guessed by now, Sandoz launched a generic version of Prezista® before the expiry of the French SPC – which is set to take place on February 23, 2019.

Another form of launch at risk.

The parties have been entangled in pan-European litigation over the darunavir SPCs. This litigation actually hit the headlines when, on January 25, 2018, the British Court of Appeal referred a question to the CJEU in relation with the validity of the British SPC.

The case is still pending and was allocated number C-114/18.

The issue at stake is the following.

Claim 1 of the EP’209 patent is a so-called Markush claim.

A Markush claim covers a large class of chemical compounds by way of a generic formula, without reciting them individually. In this case, the generic formula contained in claim 1 is the following:

Each group among P1, P2, R2, R3 and R4 is defined as being selected among of list of possible options. I will spare you the complete lists here. But it may be important to note that each list itself recites generic classes of groups, rather than individualized groups. For instance P1 and P2 can be alkoxycarbonyl groups, aralkoxycarbonyl groups, alkylcarbonyl groups, etc. Each of these options encompasses an unknown number of individual possibilities. In the end, the array of choices falling under the generic formula is practically unlimited.

Well, not quite. In fact the number of theoretical possibilities was estimated in the British litigation to be from 7 x 10135 to 1 x 10377. Not a very accurate estimate, but let’s not skimp on a couple hundred zeros.

Now, darunavir has the following structure:

It turns out to be one of the zillion compounds covered by claim 1

Several other claims of the patent also cover darunavir, but always in a generic way. Darunavir is not cited in the patent, not exemplified, nor singled out in any other manner.

Now, according to famous / infamous article 3(a) of the so-called SPC Regulation (Regulation (EC) No. 469/2009):

A certificate shall be granted if, in the Member State in which the application referred to in Article 7 is submitted and at the date of that application:

(a) the product is protected by a basic patent in force […].

As regular readers of this blog are well aware, people have been arguing, fighting and spending millions and millions of euros for a number of years over what it means for a product to be protected by a basic patent.

Some (limited) guidance has been offered by the CJEU over time.

For instance, this is from the Medeva judgment (C-322/10):

Article 3(a) of [the SPC Regulation] must be interpreted as precluding the [grant on an] SPC relating to active ingredients which are not specified in the wording of the claims of the basic patent relied on in support of the SPC application.

Then there is the Eli Lilly judgment (C-493/12):

Article 3(a) of [the SPC Regulation] must be interpreted as meaning that, in order for an active ingredient to be regarded as ‘protected by a basic patent in force’ within the meaning of that provision, it is not necessary for the active ingredient to be identified in the claims of the patent by a structural formula. Where the active ingredient is covered by a functional formula in the claims of a patent issued by the EPO, Article 3(a) of that regulation does not, in principle, preclude the grant of an SPC for that active ingredient, on condition that it is possible to reach the conclusion on the basis of those claims, interpreted inter alia in the light of the description of the invention, as required by Article 69 of the EPC and the Protocol on the interpretation of that provision, that the claims relate, implicitly but necessarily and specifically, to the active ingredient in question […].

And let’s not forget about Teva (C-121/17):

Article 3(a) of [the SPC Regulation] must be interpreted as meaning that a product composed of several active ingredients with a combined effect is ‘protected by a basic patent in force’ within the meaning of that provision where, even if the combination of active ingredients of which that product is composed is not expressly mentioned in the claims of the basic patent, those claims relate necessarily and specifically to that combination. For that purpose, from the point of view 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 those active ingredients must necessarily, in the light of the description and drawings of that patent, fall under the invention covered by that patent, and each of those active ingredients must be specifically identifiable, in the light of all the information disclosed by that patent.

And there are a few other relevant ones.

But the thing is, the CJEU has never ruled so far on how article 3(a) should be applied with respect to a Markush claim. So, in this case, should darunavir be considered as being “specified in the wording of the claims” (as per Medeva)? Is it possible to conclude that the claim “relates, implicitly but necessarily and specifically“, to darunavir (as per Eli Lilly)? Or is this not a relevant question as the claim should not be considered as a functional claim? Or maybe a combination of substituents in a Markush formula should be treated like a combination of active compounds, so that it should be investigated whether, “from the point of view 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“, each of the substituents is “specifically identifiable, in the light of all the information disclosed by that patent” (as per Teva)?

Of particular interest in this case is that, not only was darunavir not known as a compound at the filing date and was only made available several years later; but group P1 of the generic formula, when the formula applies to darunavir, can be considered as an unusual group at the filing date, which does not form part of common general knowledge.

The British Court of appeal thus proposed the following question for the CJEU:

Where the sole active ingredient the subject of [an SPC] issued under [the SPC Regulation] is a member of a class of compounds which fall within a Markush definition in a claim of the patent, all of which class members embody the core inventive technical advance of the patent, is it sufficient for the purposes of Article 3(a) of the SPC Regulation that the compound would, upon examination of its structure, immediately be recognised as one which falls within the class (and therefore would be protected by the patent as a matter of national patent law) or must the specific substituents necessary to form the active ingredient be amongst those which the skilled person could derive, based on their common general knowledge, from a reading of the patent claims?

And this now brings us to France.

Sandoz obtained a Marketing authorization (MA) for the generic version of Prezista® on December 15, 2017. Searle and Janssen issued multiple warnings to Sandoz and then discovered in December 2018 that the generic drug (Darunavir Sandoz) was on the French market.

On December 14, 2018, they filed a complaint against Sandoz in urgency proceedings (référé d’heure à heure) for infringement of their SPC No. FR’034 – after getting an authorization to do so from the court.

Sandoz’ sole defense relied on the invalidity of the SPC for non-compliance with art. 3(a) the SPC Regulation. 

The hearing took place one week only after the filing of the complaint, on December 21, 2018. Then the judge Ms. Lignières took the case home during the Christmas break and issued her decision on January 11, 2019, ruling against Sandoz.

In the decision, the judge analyzed the CJEU case law and came to the conclusion that the Eli Lilly test is not applicable to a Markush claim:

It should be noted that, in the Eli Lilly decision, the case related to a functional claim, so that the CJEU insisted on a double condition of necessity and specificity. In the present case, the claims of the basic patent are structural and better allow the skilled person to determined in view of the claims whether the active compound protected by the SPC was covered by the basic patent. 

Then, after analyzing the formula of claim 1 of the patent and the various meanings of the variable groups in this claim and some of the dependent claims, the court concluded that:

Therefore darunavir is identified by the skilled person as being implicitly but necessarily and specifically protected by the EP’209 patent in view of the substituents identified in the claims, in keeping with the requirements of article 3(a) of the EC Regulation and of the CJEU case law.

The judge thus considered that the defendant did not prove that the SPC was manifestly invalid.

Accordingly, a preliminary injunction was ordered, under a 50,000 euro-penalty per violation of the injunction. The judge also ordered a seizure of the infringing drugs, as well as a product recall.

I don’t have an exhaustive view of the pan-European Searle v. Sandoz litigation, but at least in the Netherlands a similar preliminary ruling was issued a couple of months earlier: see here.

In a recent post I wondered whether there was a surge in preliminary injunctions in France these days. The darunavir case seems to provide a confirmation. 

We will have to wait for the CJEU ruling to know whether the French judge correctly guessed which way the Luxembourg winds will finally blow.

But at any rate this decision should reassure IP right holders. A very quick preliminary decision can be issued in France when time is of the essence. Therefore, launching a generic drug a couple of months before the expiry of the IP at stake does not curtail the injunctive risk.


CASE REFERENCE: TGI Paris, ordonnance de référé, January 11, 2019, GD Searle LLC et al. v. SAS Sandoz, RG No. 18/60334

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