A travel back in time

Regular readers of this blog are probably aware that Lionel Vial is a frequent contributor.

I am grateful for his thorough reporting on pharma / biotech case law. Today, he once again keeps us apprised of the latest SPC tidbit. As he even provided the illustration, I really have nothing to add but say thanks!

While we are all waiting for the decision of the CJEU in the Santen case (C-673/18) to finally know if, in application of the Neurim (C-130/11) case law, a patented novel medical use in humans of a product having already been authorized for a previous different medical use in humans deserves a supplementary protection certificate (SPC), the decision discussed today will take us back to the pre-Neurim era, a time of uncertainty as we will see.

At that time, the prevailing case law regarding further medical use consisted in Pharmacia Italia SpA (C-31/03) rendered on October 19, 2004, and Yissum (C-202/05) rendered on April 17, 2007.

According to the judgment in Pharmacia Italia SpA:

The grant of a supplementary protection certificate in a Member State of the Community on the basis of a medicinal product for human use authorised in that Member State is precluded by an authorisation to place the product on the market as a veterinary medicinal product granted in another Member State of the Community before the date specified in Article 19(1) of Council Regulation No 1768/92 of 18 June 1992 concerning the creation of a supplementary protection certificate for medicinal products.

On the other hand, the order in Yissum reads:

Article 1(b) of Council Regulation (EEC) No 1768/92 of 18 June 1992 concerning the creation of a supplementary protection certificate for medicinal products […] is to be interpreted as meaning that in a case where a basic patent protects a second medical use of an active ingredient, that use does not form an integral part of the definition of the product.

The DeLorean remains the best way to travel in time with style.

The Regents of the University of Colorado (hereafter the University) was granted European patent No. 1658858 on November 18, 2009 for the use of a botulinum toxin, in particular botulinum toxin type A, in the preparation of a pharmaceutical composition for treating a recalcitrant voiding dysfunction, in particular urinary incontinence.

A corresponding marketing authorization was then granted on August 22, 2011.

The University had six month (that is until February 22, 2012) to file an SPC application. However, since botulinum toxin type A had benefited of previous marketing authorizations and in view of the then prevailing case law, the University considered it impossible to have an SPC granted and therefore no SPC application was filed.

Then the Neurim judgment was rendered on July 19, 2012. It notably provides that:

Articles 3 and 4 of Regulation (EC) No 469/2009 of the European Parliament and of the Council of 6 May 2009 concerning the supplementary protection certificate for medicinal products must be interpreted as meaning that, in a case such as that in the main proceedings, the mere existence of an earlier marketing authorisation obtained for a veterinary medicinal product does not preclude the grant of a supplementary protection certificate for a different application of the same product for which a marketing authorisation has been granted, provided that the application is within the limits of the protection conferred by the basic patent relied upon for the purposes of the application for the supplementary protection certificate.

Neurim has often been considered as a complete reversal of the previous case law.

Besides, for many commentators, it opened the door to SPCs for novel medical uses in humans of products having already been authorized for a previous different medical use in humans.

The University therefore filed an SPC application on September 19, 2012, i.e. within 2 months of the publication of the Neurim judgment, but about 7 months after the end of the deadline for doing so.

The University sought to benefit from the provisions of Article L. 612-16 of the Code de la propriété intellectuelle, according to which:

Where an applicant has not complied with a time limit as regards the Institut National de la Propriété Industrielle, it may submit an appeal for reinstatement of it rights if it is able to give a legitimate reason and if the direct consequence of the hindrance has been refusal of its patent application or of a request or the loss of any other right or means of appeal.

The appeal must be submitted to the Director of the Institut National de la Propriété Industrielle within two months of the cessation of the hindrance. The act that has not been carried out must be accomplished within that period. The appeal shall only be admissible within a period of one year from expiry of the time limit not complied with. […]

However, the INPI (French patent office) was not convinced and rejected the appeal for reinstatement on June 30, 2015.

The University and Allergan (to whom the SPC application and the basic patent had then been assigned) appealed the decision of the Director of the INPI before the Paris Cour d’appel on September 18, 2015.

In a first decision dated September 16, 2016 the Cour d’appel confirmed the decision of the INPI. However, the decision was invalidated by the Cour de cassation, the French Supreme court, on April 5, 2018, for procedural reasons, as the Cour d’appel had neglected notifying observations made by the INPI to the University and Allergan.

The case then came back in front of the Paris Cour d’appel which, albeit with different judges, again confirmed the decision of the INPI on February 12, 2019 in the following terms:

However, according to the terms of article L. 612-16 of the intellectual property code, the legitimate reason must be understood as a “hindrance”;

Even considering that the case law of the CJEU, before the Neurim judgement, did not allow the University to expect obtaining an SPC and could therefore discourage it to file an SPC application, the director of the INPI rightly observes that this situation does not characterize a hindrance according to the previously cited provision, given that the case law, be it that of the Court of justice, evolves, that even with the Pharmacia Italia and Yissum case law other operators have indeed filed SPC applications in relation to further medical uses, one of which having given rise to the Neurim judgment, and that the lack of filing of an SPC application by the University was the result of its free appreciation of the latter and not of an objective impossibility, independent of its will.

In any case, pursuant to article 7 of regulation No. 469/2009 concerning the supplementary protection certificate for medicinal products, the University had a six-month period expiring on February 22, 2012 to file its SPC application; the reference for preliminary ruling to the Court of justice of the European Union was received at the Court on March 16, 2011 and published in the OJEU on June 18, 2011; under these conditions, as is rightly observed by the director of the INPI, the University had to consider a possible reversal of the case law of the Court of justice;

As such, the decision of the director of the INPI is exempt from criticism in having retained that the lack of respect of the deadline imparted to the University for filing its SPC application was not due to a hindrance for which it would benefit from a legitimate reason, but to its will not to proceed with a filing that it did not consider appropriate and this in spite of the reference for a preliminary ruling submitted to the Court of justice duly published on June 18, 2011.

Perhaps, this case is an illustration that too much knowledge is sometimes dangerous, and that we, as counsels, should always be careful when giving opinions on the likely outcome of a filing on the basis of our knowledge of established case law, bearing in mind that there is always a possibility, even a remote one, that a case law can be overturned.

In any case, the University and Allergan should refrain from nourishing regrets on their missed filing at least until the result of the Santen referral (C-673/18) is known, as this latter case precisely arises from a decision of rejection of an SPC application by the INPI in relation to a further medical use.

Well, the way I see it, getting SPC law 100% right is a little bit like having to hit a wire with a connecting hook at precisely eighty-eight miles per hour the instant a lightning strikes a tower. Everything will be fine.


CASE REFERENCE: Cour d’appel de Paris, pôle 5 chambre 1, February 12, 2019, The Regents of the University of Colorado & Allergan Inc. v. Directeur de l’Institut National de la Propriété Industrielle, RG No. 18/14291.

A saga with twists

As promised last week, here is another episode of the ezetimibe SPC saga. Just like last week, Lionel Vial reports on the latest twists.

After having applied, on the basis of European patent EP0720599 (EP’599), for a first French SPC for ezetimibe alone (FR03C0028), then for a second one for ezetimibe in combination with simvastatin (FR05C0040), Merck Sharp & Dohme Corp. (Merck) has sought to secure a third one for ezetimibe in combination with atorvastatin (FR14C0068) corresponding to the medicinal product Liptruzet®.

However, if the first two SPC applications were granted by the INPI (French patent office), the third application was met with a decision for refusal that Merck appealed.

It is the appeal decision, rendered on January 22, 2019, that we will discuss today.

The 1960s, a decade of many twists – now, that’s a far-fetched one.

As a reminder from our previous post, EP’599 specifically claims ezetimibe in claim 8 and a pharmaceutical composition for the treatment or prevention of atherosclerosis, or for the reduction of plasma cholesterol levels, comprising an effective amount of ezetimibe, alone or in combination with a cholesterol biosynthesis inhibitor selected from the group consisting of lovastatin, pravastatin, fluvastatin, simvastatin, CI-981, DMP-565, L-659,699, squalestatin 1 and NB598, in a pharmaceutical acceptable carrier (claim 17).

Cl-981 is atorvastatin, a statin (i.e. an inhibitor of cholesterol biosynthesis) that was known before the filing date of the patent. The patent discloses results of biological tests obtained for ezetimibe alone (compound 6a in the last table of the example section of the patent) but does not disclose experimental results specifically obtained for a combination of ezetimibe and atorvastatin.

SPC application No. FR14C0068 was filed for ezetimibe in combination with atorvastatin or the pharmaceutical acceptable salts thereof, including the calcium salt of atorvastatin.

The INPI rejected the application on February 6, 2018 for lack of compliance with article 3(c) of Regulation (EC) No. 469/2009 (“the SPC regulation”) which provides that a certificate shall be granted if, at the date of the application for an SPC, “the product has not already been the subject of a certificate“.

The INPI mainly based its rejection on the previously granted SPC of ezetimibe alone (FR03C0028) and on the decision of the Court of Justice of the European Union (CJEU) in case C-443/12 (Actavis v. Sanofi, Irbesartan):

Where, on the basis of a patent protecting an innovative active ingredient and a marketing authorisation for a medicinal product containing that ingredient as the single active ingredient, the holder of that patent has already obtained a supplementary protection certificate for that active ingredient entitling him to oppose the use of that active ingredient, either alone or in combination with other active ingredients, Article 3(c) of [the SPC Regulation] must be interpreted as precluding that patent holder from obtaining – on the basis of that same patent but a subsequent marketing authorisation for a different medicinal product containing that active ingredient in conjunction with another active ingredient which is not protected as such by the patent – a second supplementary protection certificate relating to that combination of active ingredients.

Subsidiarily, the INPI considered that even if the combination of ezetimibe with an HMG-coA reductase (i.e. a statin) could be considered to constitute a different innovation from ezetimibe alone, which the INPI denied, then SPC No. 05C0040 (for ezetimibe in combination with simvastatin) would be opposable to the grant of a new SPC.

Merck lodged an appeal against the decision of rejection before the Paris Cour d’appel on May 4, 2018.

During the proceedings, the INPI came to agree with the appellant that the combination of ezetimibe and atorvastatin complied with the requirements of article 3(a) of the SPC.

The only question that the Cour d’appel had to answer was therefore whether the combination of ezetimibe with atorvastatin is a different product from ezetimibe alone or from the combination of ezetimibe and simvastatin.

Let’s see what the Cour d’appel decided:

The combination of the statin atorvastatin with ezetimibe must constitute a product – within the meaning of the regulation – different from the combination of the simvastatin statin with ezetimibe, subject of SPC No. 05C0040, in order for the condition of article 3(c) of the regulation to be fulfilled.

However, claim 17 of the patent gives a list of the different statins with which ezetimibe can be combined indifferently and without distinguishing them, and the combination of ezetimibe with a statin as provided by [claim] 17 has already been the subject of SPC No. 05C0040 granted for the combination of ezetimibe and simvastatin; it is not justified within the terms of the patent that the result of the combination of ezetimibe with atorvastatin constitutes a different product from the combination of ezetimibe with simvastatin.

The 599 patent relates to “hydroxy-substituted azetidinone compounds useful as hypocholesterolemic agents in the treatment and prevention of atherosclerosis, and to the combination of a hydroxy-substituted azetidinone of this invention and a cholesterol biosynthesis inhibitor for the treatment and prevention of atherosclerosis” and SPC No. 05C0040 has been granted for the combination of ezetimibe with a cholesterol biosynthesis inhibitor, simvastatin, so that the combination of ezetimibe with another statin, atorvastatin, which is not protected as such by the patent, cannot justify the grant of anew SPC.

The condition of article 3(c) being unfulfilled because of SPC No. 05C0040 “ezetimibe in combination with simvastatin” the appeal of MSD against the decision dated February 5, 2018 of the Director of the INPI will be rejected.

To summarize, the Cour d’appel has decided that the EP’599 basis patent protected as such two different products: (i) ezetimibe and (ii) ezetimibe in combination with a statin.

Besides, the Cour d’Appel has also decided that the various particular statins cited in claim 17 were not protected as such, so that the combination of ezetimibe with atorvastatin could not be distinguished from the combination of ezetimibe with simvastatin, both of them being variations of the same product “ezetimibe in combination with a statin”. Therefore, the combination of ezetimibe with a statin, in particular atorvastatin was already the subject of an SPC (FR05C0040 for a combination of ezetimibe with a statin, in particular simvastatin).

In deciding so, and in relation to the preliminary injunction previously discussed based on SPC FR05C0040 (covering the drug Inegy®), it could be hypothesized that the Cour d’appel has acknowledged that the product ezetimibe in combination with simvastatin is protected as such by the EP’599 patent and is different from the product ezetimibe. However, this would be a dramatic change over the previous decision of the Cour d’appel regarding this SPC (discussed here).

Let’s take this occasion to try to summarize the ezetimibe saga so far:

Product SPC Drug Generic company Decision type Date Result
Ezetimibe + simvastatin FR05C0040 Inegy® Biogaran Appeal following preliminary injunction (CA Paris) 2018/06/26 Preliminary injunction denied (SPC likely invalid)
Ezetimibe + simvastatin FR05C0040 Inegy® TEVA Judgement (TGI Paris) 2018/10/25 SPC valid
Ezetimibe + atorvastatin FR14C0068 Liptruzet® Appeal (CA Paris) 2019/01/22 SPC rejected
Ezetimibe + simvastatin FR05C0040 Inegy® Mylan Preliminary injunction (TGI Paris) 2019/03/07 Preliminary injunction granted (SPC likely valid)

Needless to say, we are eagerly awaiting the next decisions of the Cour d’appel to see more clearly which direction the French case law is taking in matters of combination SPCs.

Many thanks as always Lionel for the thorough summary. This truly is a murky subject.

Lionel’s working hypothesis on the decision is that the court may have acknowledged that the product ezetimibe in combination with simvastatin is different from the product ezetimibe. But this is really a matter of interpretation of the ruling. In my view the ruling states that the product ezetimibe in combination with atorvastatin is the same as the product ezetimibe in combination with simvastatin but does not take a clear position on the product ezetimibe in combination with (any) statin compared with the product ezetimibe alone.

The thing is, during the court proceedings, the INPI simply relied on the existence of the prior combo SPC FR05C0040 and not (i.e. no longer) on the existence of the mono SPC FR03C0028 as a reason for objecting to the second combo SPC. Thus, the court did not have to rule on the comparison with the mono SPC.

Also, it can be noted that the January 22 ruling was issued by exactly the same panel as the one that held that the first combo SPC was likely invalid last June.

It is certainly possible that these judges may have changed their minds in this respect since then but to me the second ruling is inconclusive in this respect.

To be continued, definitely.


CASE REFERENCE: Cour d’appel de Paris, pôle 5 chambre 1, January 22, 2019, Merck Sharp & Dohme Corp. v. Directeur Général de l’INPI, RG No. 18/10532

The new normal

What the heck is going on with preliminary injunctions (PIs) in France right now?

Let’s face it, France is not particularly renowned for its patentee-friendliness. But different winds seem to be blowing these days over the Batignolles. Is this mere happenstance? Could it have anything to do with recent judicial appointments? Is there a feeling among our judges that the pendulum should swing back a little bit towards IP right holders? Or has there been a change in the behavior of third parties?

Preliminary injunctions in France: the new normal?

Hard to tell of course, so readers will have to make their own opinion based on a report kindly provided by Lionel Vial on a PI issued just a few days ago. I will now leave him the floor.

There has been a second high-penalty preliminary injunction in a row in the pharma field that we will comment on today after Renaud’s post on darunavir.

The drug at stake is a combination of ezetimibe and simvastatin (Inegy®, MSD France) which is prescribed for reducing cholesterol levels. Ezetimibe reduces intestinal absorption of cholesterol while simvastatin is a HMG-CoA reductase inhibitor (i.e. a statin) which inhibits cholesterol biosynthesis.

The case opposes Mylan, which has been marketing a generic version of the combination since April 18, 2018, and Merck (Merck Sharp & Dohme Corp. & MSD France) before the Paris Tribunal de Grande Instance (TGI).

Merck Sharp & Dohme Corp. holds French Supplementary Protection Certificate (SPC) FR05C0040, of which MSD France is a licensee. The SPC is based on European patent EP0720599 (EP’599) for the product “ezetimibe optionally in the form of its pharmaceutical acceptable salts in combination with simvastatin” and is set to expire on April 2, 2019.

EP’599 specifically claims ezetimibe in claim 8 and a pharmaceutical composition for the treatment or prevention of atherosclerosis, or for the reduction of plasma cholesterol levels, comprising an effective amount of ezetimibe, alone or in combination with a cholesterol biosynthesis inhibitor selected from the group consisting of lovastatin, pravastatin, fluvastatin, simvastatin, CI-981, DMP-565, L-659,699, squalestatin 1 and NB598, in a pharmaceutical acceptable carrier (claim 17).

On October 17, 2017, Mylan started nullity proceedings against the SPC, to which Merck responded by requesting, on November 30, 2018, that a preliminary injunction to stop selling the ezetimibe/simvastatin combination and to pay provisional damages be issued against Mylan.

Mylan countered that the SPC was invalid because:

    • It was granted for a combination which is not protected as such by the basic patent, in breach of Article 3(a) of the SPC regulation (No. 469/2009), since it would not form the core inventive advance of the patent, which is centered on ezetimibe, in particular in the absence of any research conducted on the ezetimibe/simvastatin combination.
    • The product protected by the basic patent had already been the subject of a certificate (i.e. SPC FR03C0028 granted for ezetimibe) in breach of Article 3(c) of the SPC regulation.

However, principally applying C-121/17 (Teva UK Ltd. et al. vs. Gilead Sciences Inc.), the judge in charge of case management (JME) decided on March 7, 2019 that:

The Court of Justice of the European Union thus considers that a product which is a combination of active ingredients is “protected by a patent in force” 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. The product must, from the point of view of a person skilled in the art and in the light of the description and drawings of the basic patent, necessarily fall under the invention covered by that patent and each active ingredient must be specifically identifiable.

As such, a product which is a combination of active ingredients pursuant to the first article of regulation (EC) No. 469/2009, necessarily relates to the invention covered by the patent if each of these ingredients is specifically identifiable according to the claims of the patent, without it being necessary that the second active ingredient of the combination be a new compound taught by the patent and protectable on that basis.

In this regard, in view of the GILEAD decision, the Court of Justice of the European Union does not require that the active ingredients, the combination of which is intended, should be an invention of the basic patent, provided [these ingredients] are identifiable. [The Court] only holds that the combination must necessarily relate to the invention covered by that patent.

This thus applies to a novel composition relating at least to an active ingredient taught by the patent.

[…]

Claim 17 of the patent claims a pharmaceutical composition according to claim 16 (which relates to the pharmaceutical composition according to any of claims 9, 12 or 15 wherein the cholesterol biosynthesis inhibitor is selected from the group consisting of HMG CoA reductase inhibitors), wherein the cholesterol biosynthesis inhibitor is selected from a group to which simvastatin belongs.

The association ezetimibe/simvastatin, which is thus taught, therefore necessarily relates to the invention deriving from the basic patent, simvastatin being specifically identified by the patent.

The product sold under the trademark INEGY®, which is a combination of the active ingredients ezetimibe and simvastatin, therefore appears to be “protected by a basic patent in force”, pursuant to article 3(a) of regulation (EC) No. 469/2009.

It is reminded that pursuant to article 3(c) of this regulation, the SPC can only be granted if the product has not already been the subject of a previous SPC.

The condition provided by article 3(c) of regulation (EC) No. 469/2009 therefore also appears to be fulfilled.

As such, the arguments put forward by MYLAN to demonstrate that there is a doubt as to the validity of SPC No. 05C0040 appear to be lacking seriousness, this SPC obviously fulfilling the requirements of article 3 of regulation (EC) No. 469/2009. It can neither be seriously argued against the sufficiency of disclosure nor against the inventive step, since these conditions are not envisioned by article 3 of the regulation for obtaining a SPC, due note being taken that the disclosure of the ezetimibe/simvastatin combination allows the one skilled in the art to easily reproduce it, while this combination was not known at the filing date of the basic patent.

It follows that by marketing, since April 18, 2018, the generics “EZETIMIBE/SIMVASTATIN MYLAN” comprising a combination of ezetimibe and simvastatin, in violation of SPC No. 05C0040 granting the market exclusivity of this combination to MSD, MYLAN likely infringed.

Too bad for what appears to have been a test by Mylan of the application in France of Justice Arnold’s proposal that, in order to be granted an SPC, a product must infringe the basic patent because it contains an active ingredient, or a combination of active ingredients, which embodies the inventive advance (or technical contribution) of the basic patent.

It is also very surprising that there has been a complete change of appreciation of the validity of this SPC, since on April 5, 2018 the judge in charge of urgency proceedings refused to issue a preliminary injunction against Biogaran on the basis of the same SPC because the latter was considered likely invalid, which was confirmed on appeal on June 26, 2018 (see Renaud’s post on the subject here). But then, C-121/17 (July 25, 2018) had not been issued yet and the Cour d’appel mostly relied on C-443/12 (Actavis Group PTC EHF & Actavis UK Ltd v. Sanofi).

However, perhaps the interpretation of the evolving case law of the CJEU by French judges is not the most notable part of this decision.

Indeed, the following substantial damages were awarded:

    • 2,901,779 euros to MSD France
    • 1,460,889 euros to Merck Sharp & Dohme Corp.

As a reminder, in the darunavir case (GD Searle LLC et al. v. SAS Sandoz) the judge in charge of urgency proceedings ordered on January 11, 2019 a preliminary injunction against Sandoz, under a 50,000 euro-penalty per violation of the injunction (Renaud’s post on the subject).

Before that, on June 7, 2018, the judge in charge of case management awarded 5,846,628 euros to Novartis Pharma AG and 7,308,285 euros to Novartis Pharma SAS as provisional damages in the valsartan/amlodipine patent infringement case (see here for a report).

Besides, a preliminary injunction was also recently issued on July 6, 2018 against a potential infringer in a chemistry case, but without provisional damages (see here for a report by Renaud).

Therefore, we may be currently observing a new trend setting in that could make France a very attractive forum for preliminary injunctions, in particular in the pharma field.

An open question is whether this trend could weigh in favor of Paris in relation to the still undecided relocation of the London UPC central division, which is in particular competent for pharmaceuticals.

Out of luck for the time being (the decision on the merits is yet to come) with the ezetimibe/simvastatin combination, maybe Mylan could consider a combination of ezetimibe with atorvastatin, since a recent decision from the Paris Cour d’appel rendered on January 22, 2019 has upheld the decision of the Director of the INPI (French Patent Office) to reject French SPC application No. 14C0068 for “ezetimibe in combination with atorvastatin or pharmaceutically acceptable salts thereof, including the calcium salt of atorvastatin”. But that will be our next post on Patent My French, so stay tuned for more on SPCs!

As always I would like to thank Lionel for this thorough report. The story does indeed need to continue with this appeal ruling of January 22, 2019, which in my view is closely connected to today’s decision – and (spoiler alert) there is a new twist in the saga.


CASE REFERENCE: Tribunal de grande instance de Paris, 3ème chambre 1ère section, ordonnance du juge de la mise en état, October 17, 2017, Mylan v. Merck Sharp & Dohme Corp. & MSD France, RG No. 17/14664.

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

Doppelgänger

The names of the parties in the case commented upon today first reminded me of the classic movie Kramer vs. Kramer. But you could also think about the Doppelgänger.

See, the case at hand is Novartis v. Novartis or, to be more precise, SAS Novartis Pharma v. Novartis Pharma AG.

The judgment is very short and utterly uninteresting in itself, but as you will see the underlying context is much more noteworthy.

Let’s start with the judgment per se first.

Novartis Pharma AG is the owner of European patent No. EP 1096932 entitled “Combined use of valsartan and calcium channel blockers for therapeutic purposes“.

Novartis Pharma AG is also the owner of French SPC No. 07C0042, which was granted in 2008. This SPC is based on the EP’932 patent and on a European Marketing authorization (MA) and is directed to a medicinal product comprising the two active substances valsartan and amlodipine.

The corresponding commercial drug marketed by the Novartis group is Exforge®.

The EP’932 patent was opposed by 8 different opponents at the EPO. In first instance, the patent was maintained in amended form by the opposition division.

On appeal, after the issuance of the summons to oral proceedings, Novartis Pharma AG withdrew all its requests and disapproved of the text of the patent, which led to the revocation of the patent on October 7, 2015.

On January 29, 2018, another company from the Novartis group, namely SAS Novartis Pharma, filed a complaint with the Paris Tribunal de grande instance (TGI) and requested that the TGI should revoke SPC No. 07C0042, as a consequence of the revocation of the basic patent.

The “defendant” Novartis Pharma AG agreed, and the court thus pronounced the requested revocation of the SPC on April 5, 2018.

Let me introduce the bunny and his feline Doppelgänger.

Now, in case you are wondering, of course the various Novartis companies have not run amok.

No, this unusual ruling seems to be the result of a very elaborate strategy, which can be (at least partly) comprehended based on publicly available information.

The first thing you need to know is that two divisional applications were filed based on the EP’932 patent.

The first one was deemed to be withdrawn, but the second one led to the grant of another patent, EP 2322174. On the face of it, the EP’174 patent contains claims which are somewhat similar to those of EP’932, and which still cover the combination of valsartan and amlodipine.

The second important thing is that another French SPC application (No. 16C0008) was filed based on the divisional patent EP’174, still for the combination of valsartan and amlodipine, on March 7, 2016 (thus a few months after the grant of EP’174 on September 15, 2015 and after the revocation of the parent EP’932 patent on October 7, 2015).

Based on publicly available information, the second SPC was initially granted in June 2016. But then, three months later, on September 26, 2016, the decision to grant the SPC was withdrawn by the INPI (French patent office). Indeed, the withdrawal or cancellation of any decision issued by the INPI is possible as a matter of principle within a four-month time limit.

Examination of SPC application No. 16C0008 was immediately resumed, and an office action was issued, in which an objection was raised based on the existence of the prior SPC No. 07C0042. As a reminder, article 3(c) of the SPC regulation (aka Regulation (EC) No. 469/2009 of the European Parliamant and of the Council of May 6, 2009) provides that a certificate can only be granted if “the product has not already been the subject of a certificate“.

As a first line of defense, Novartis replied that the revocation of the EP’932 patent also automatically entails the annihilation of the first SPC No. 07C0042, in a retroactive manner. Therefore, they argued, the valsartan + amlodipine product in the second SPC application No. 16C0008 had not already been the subject of a certificate.

But the INPI was not convinced and maintained its objection.

With that in mind, the strange Novartis v. Novartis action suddenly becomes much more understandable.

Novartis’ purpose was to obtain an official ruling from a court of law per which the first SPC was revoked. This strengthened their argument with the INPI. And the strategy was successful, as the objection based on article 3(c) of the SPC regulation was overcome and the second SPC was finally granted (for the second time) in June 2018.

Based on the arguments submitted by Novartis which can be read in the SPC file wrapper, second SPCs replacing the first round of SPCs were also obtained in a similar manner in a number of other European countries.

At this stage, one question remained for me: why did Novartis find it useful to surrender its parent patent and all SPCs obtained based on it, and to start the entire procedure from scratch based on the divisional patent and a second set of SPC applications?

Well, sometimes a blogger has to play detective. Comparing the two different SPC applications, it appears that both are based on the same MA having effect in France, namely European MA No. EU/1/6/371/001-24. But then one difference immediately becomes obvious in the next box of the application form.

In the first SPC application, the first MA obtained in the Community or EEE is indicated as being this same MA No. EU/1/6/371/001-24, dated January 16, 2007. But in the second SPC application, the first MA obtained in the Community or EEE is indicated as being a slightly earlier Swiss MA No. 57771/01-03, dated December 22, 2006. Actually, since the AstraZeneca judgment of the CJEU (C-617/12), we have known that Swiss MAs count as potential first MAs in the Community or EEE, as they are automatically recognized in Liechtenstein.

So the Doppelgänger mystery is solved – I think: the initial SPC application contained a mistake, in that the indication of the first MA obtained in the Community or EEE was not correct. Hence the need to get rid of the first patent and first SPC, in order to obtain a corrected SPC based on the second patent.  

I would be curious to know whether Novartis’ clever strategy succeeded in all European countries or whether it failed in some of them.

More generally, I would be curious to know what readers make of all this.

Should the revocation of a first SPC indeed make it possible to request a second SPC as if the first SPC had never been granted?

This does raise policy issues. Imagine that the first SPC had been revoked further to a nullity suit filed by a true third party. Would it be fair to allow the SPC owner to obtain a second SPC essentially identical to the first one, based on a divisional patent?

At any rate, this case will probably be a further incentive to file divisional applications for important inventions which could potentially be protected by an SPC. More than ever, divisional applications appear to be a very powerful (some would say, too powerful) tool in the hands of IP right holders.


CASE REFERENCE: TGI de Paris, 3ème chambre, 1ère section, April 5, 2018, SAS Novartis Pharma v. Novartis Pharma AG, RG No. 18/02118.