CJEU asked to clarify protections available to ‘combination’ medicines

The latest questions on the issue referred to the Court of Justice of the EU (CJEU) have been set by Ireland’s Supreme Court in a case involving rival pharmaceutical manufacturers Merck Sharp & Dohme (MSD) and Clonmel Healthcare.

Experts in intellectual property dispute resolution at Pinsent Masons said the legal points at issue in the case are of significant interest within the life sciences sector.

SPCs are provided for in EU law, and separately too in UK law post-Brexit, to enable pharmaceutical patent holders to effectively extend the period for which they can exercise monopoly rights over the sale of medicinal products they have invested a lot of time and money into developing. Patent protection lasts 20 years but it takes drugs companies several years to develop new medicines, carry out mandatory clinical trials and gain marketing authorisation. This means that the period of patent protection available to pharmaceutical manufacturers during which they can commercialise their products is typically much shorter than that which applies in other, less regulated, sectors. The SPC framework was developed to account and compensate for that.

In the EU, pharmaceutical companies are only eligible for SPCs if they meet the criteria for protection under the 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 – as stipulated by Article 3(a); a marketing authorisation has been issued to place that product on the market as a medicinal product – as stipulated by Article 3(b); an SPC has not already been issued for the product – as stipulated by Article 3(c); and a marketing authorisation to place the product on the market as a medicinal product has not already been issued – as stipulated by Article 3(d).

The questions posed by the Irish Supreme Court are focused on the application of the criteria under Articles 3(a) and 3(c).

One of the issues the Irish court is seeking guidance on is the extent to which the Article 3(c) requirement – that an SPC has not already been issued for the product – limits the grant of SPCs in cases where the claims made about the underlying patent cover both a single novel molecule on its own and its use in combination.

Specifically, the court wants to know whether in those circumstances the grant of an SPC is possible for both a novel molecule if it is marketed as a single product and also to that molecule’s use in combination, or whether it is limited to one SPC for to the first marketed product covered by the patent whether this is the monotherapy of the drug covered by the basic patent in force or the first combination therapy, or whether in fact the patent holder can choose which of those options the SPC obtained for irrespective of the date of marketing authorisation.

The Irish Supreme Court has put the questions to the CJEU to help it resolve a dispute that concerns a product called Inegy, which was developed by MSD to help lower cholesterol.

Inegy combines ezetimibe with simvastatin. Ezetimibe inhibits the reabsorption of cholesterol in the human body, while simvastatin is a type of statin that is known to lower cholesterol in the bloodstream. MSD was granted a marketing authorisation to sell tablets of the combination product featuring any one of four specific compositions of ezetimibe with simvastatin in 2005.

MSD had previously, in 2003, been granted a marketing authorisation for another product called Ezetrol. That authorisation permitted the marketing of 10mg tablets of ezetimibe for treating homozygous familial hypercholesterolemia (HoFH) – a condition that children are born with that makes them susceptible to high cholesterol as a result of their genetic make-up passed down by their parents. The authorisation provided for the tablets to be co-administered with a statin.

In response to proceedings issued by MSD against Clonmel in relation to infringement of its SPC for Inegy, Clonmel Healthcare raised several legal challenges as to why it believes Inegy is not eligible for an SPC, with mixed success so far.

Last year, the Court of Appeal in Dublin ruled that while Inegy conformed to the Article 3(d) criteria – because, on the basis of the differences between Inegy and Ezetrol, it considered a marketing authorisation to place the combination product on the market had not already been issued – it nevertheless failed to satisfy two of the other criteria under Article 3 of the SPC Regulation.

In relation to Article 3(a), the Court of Appeal held that the product protected by the basic patent in force was ezetimibe and not the combination of ezetimibe and simvastatin, and further held that, because ezetimibe had been the subject of an earlier SPC in respect of Ezetrol, Inegy did not satisfy Article 3(c) requirements either.

MSD has brought an appeal before the Supreme Court in relation to the Court of Appeal’s findings on the Article 3(a) and 3(c) criteria. However, the Supreme Court has determined that it is bound to seek the CJEU’s guidance to help it resolve the dispute on those points.

As well as posing its question on the application of Article 3(c), the Supreme Court has asked the CJEU to clarify how Article 3(a) should be interpreted too.

The CJEU has been asked to rule on whether a product can be said to be protected by a basic patent in force if the product for which the SPC is granted is expressly identified in the patent claims, and covered by those claims and, if not, whether it is “necessary for the grant of an SPC that the patent holder, who has been granted a marketing authorisation, also demonstrate novelty or inventiveness or that the product falls within a narrower concept described as the invention covered by the patent” to meet the Article 3(a) requirements.

Should the CJEU decide that it is necessary to demonstrate that the product falls within a narrower concept described as the invention covered by the patent, it has been asked to clarify what must be established by the patent holder and marketing authorisation holder to obtain a valid SPC in such cases.

The Supreme Court also wants to know whether any or all of the possible combination products in the claims in the patent can be said to fall within the scope of the basic patent in force in cases where the underlying patent is for a particular drug but the claims in the patent show that the drug can also be used in combination with another drug.

Finally, the CJEU has been asked about how Article 3(a) applies where only one of the components in a combination product is novel and patented and it alone, or together with another component as a combination therapy falling within the patent claims, has already been granted an SPC. In those circumstances, the Supreme Court wants to know if it is possible for further SPCs to be issued for the single drug or any combination therapy beyond that covered by the first SPC.

Dublin-based Ann Henry of Pinsent Masons said: “It has not come as a surprise that the Supreme Court in Ireland decided to make this reference to the CJEU on Article 3.  Each question referred to the CJEU is interesting and worthy of consideration, in and of itself. The decision of the CJEU could have quite far-reaching implications and this reference has attracted a lot of attention from industry." 

Charlotte Weekes of Pinsent Masons in London said various national courts across Europe had reached different conclusions in relation to whether the Inegy SPC is valid. She said that this suggests it is still not entirely clear how Articles 3(a) and 3(c) of the SPC Regulation should be applied, essentially because this set of facts did not arise in the previous case law.

“It remains to be seen whether the CJEU’s answer in this case will provide the necessary clarity for the multitude of different types of SPCs that are sought,” Weekes said.

Weekes said that while the UK is no longer a part of the EU or subject to the jurisdiction of the CJEU, the UK courts have yet to issue any decisions on how Article 3 applies since Brexit, and that, as such, the CJEU’s view “will remain of interest to UK-based companies and practitioners”.

“The UK courts have not considered the Inegy SPC,” Weekes said. “In respect of Article 3(c) and combination products, the most recent judgment of the UK courts was in 2017. In that case, the High Court held that to be entitled to a second SPC on the same patent the claimed combination product must be inventive over the monotherapy alone which had been the subject of an earlier SPC.”

“The judge in that case said that ‘the question to be considered is not a conventional one of whether a claim is invalid over a particular item of prior art read in the light of the common general knowledge, but whether, given the invention … [the patent claim] represents a distinct invention such that it could in principle form the subject matter of a separate patent’. This is consistent with comments made by the Irish Court of Appeal, the Dutch Court of Appeal and the French and German courts in respect of Inegy,” she said.

Munich-based Julia Traumann, also of Pinsent Masons, said: “In Germany, Inegy had been subject to preliminary injunction proceedings at the Düsseldorf courts. In its decision, the Düsseldorf Court of Appeal indicated that Article 3(c) of the SPC-Regulation may be the basis for future CJEU referrals. It stated that previous decisions of the CJEU on Article 3(c) of the SPC Regulation have not yet defined in detail what makes the decisive qualitative difference between those constellations for which the CJEU would refuse to grant multiple SPCs despite a separate basic patent protection for the active ingredient combination, and those constellations in which it considers it possible.”

“The Düsseldorf Court of Appeal further stated that previous CJEU decisions did not relate to the legal test to be applied when assessing different constellations with different sets of facts. In a future decision, it stated, the CJEU would have to specify in binding terms what the decisive differentiation criterions are,” she said.

“The Düsseldorf Court of Appeal found it difficult to predict the outcome of such decision, and with the referral of the Irish Supreme Court in relation to Article 3(c) of the SPC Regulation, it is easy to see why. The outcome of the decision is hard to predict. In any case, it would be desirable if the CJEU provided a legal test that can be applied to many of the constellations that appear in this very important field around Article 3(c) of the SPC Regulation and combination products,” Traumann said.