TGI of Paris; Teva Pharmaceutical, Teva Santé Europe v Merck Sharp & Dohme Corp, n° RG: 16/16178 (Darts-ip reference: darts-748-080-F-fr) – 25 October 2018
Last July, the European Court of Justice (ECJ) published (C 121/17[1]) its answer to the preliminary ruling filed by the High Court of Justice (England and Wales)[2], Chancery Division (Patents Court) (United Kingdom) related to the article 3(a) 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.
The request for a preliminary ruling affords the ECJ a further opportunity to rule on the thorny issue of the criteria for determining whether an active ingredient or combination of active ingredients of a medicinal product is ‘protected by a basic patent in force’ within the meaning of article 3(a) of Regulation No 469/2009.
The question asked was always the same: should an SPC be granted for the product “A + B” when the basic patent protects the compound A and the MA is subsequently issued for the “A + B” combination?
The judge had chosen to refer a question to the ECJ because in his opinion the criterion to be applied in determining whether an association of active ingredients “A + B” is “protected by a basic patent” within the meaning of Article 3 (a) remained vague despite the many interventions of the ECJ.
Achieving a clear and consistent interpretation of Article 3 (a) in the context of association of active ingredient would be essential for two major reasons.
On the one hand, the granting of a SPC has a significant economic impact since the five years of potential additional protection per SPC can weigh four times more on the turnover obtained than the eight years protected (on average) by the basic patent.
On the other hand, the situation studied is frequent since it is not uncommon for an active ingredient A to be claimed alone in a patent but its exploitation as a medicinal product requires an association with another active ingredient B (for example in order to increase its therapeutic effect or to limit undesirable side effects), this had the consequence that the marketing authorization issued after a decade of development finally relates to the combination “A + B”.
According to the ECJ, in the C 121/17 decision, article 3a) 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.
The TGI of Paris had recently applied these guidelines in the “Teva Pharmaceutical, Teva Santé Europe v Merck Sharp & Dohme Corp” case.
According to the French judges, the ECJ decision created two tests to apply in order to know if an SPC on a combination of active ingredients should be granted.
The first test is that, from the point of view of a person skilled in the art and on the basis of the prior art at the priority date, the combination of active ingredients must necessarily, in the light of the description and drawings of the patent, fall under the invention covered by that patent. In other words, the combination must be one that the skilled person would understand, on the basis of the description and drawings and their common general knowledge, to embody the technical contribution made by the patent.
The second test is that, from the point of view of a person skilled in the art and on the basis of the prior art at the priority date, each of the active ingredients must be specifically identifiable, in the light of all the information disclosed by the patent.
In the French decision, the compound A (Ezetimib) was obviously mentioned specifically in the claims 1 to 8. The questions were more whether :
- the compound B (Simvastatin) was specifically identifiable, in the light of all the information disclosed by that patent;
- the association A (Ezetimibe) and B (Simvastatin) necessarily[3] fall under the invention covered by that patent, that is to say, the association embodies the technical contribution made by the patent.
The compound B (Simvastatin) was considered as specifically identifiable because claims 9, 16 and 17 encompass the use of a cholesterol biosynthesis inhibitors for use in the combination of the compound A (Ezetimib) including HMG CoA reductase inhibitors such as lovastatin, pravastatin, fluvastatin, simvastatin, CI-981, DMP-565, L-659, 699, squalestatin 1 and NB-598.
The description (page 5, paragraph 28) discloses that the « cholesterol biosynthesis inhibitors for use in the combination of the present invention include HMG CoA reductase inhibitors such as lovastatin, pravastatin, fluvastatin, simvastatin, CI-981, DMP-565, L-659, 699, squalestatin 1 and NB-598 ». Moreover, the description adds that « Preferred HMG CoA reductase inhibitors are lovastatin, pravastatin and simvastatin ».
Therefore, even if simvastatin is not exclusively mentioned (it is cited among 9 other HMG CoA reductase inhibitors), the judges considered it as specifically identifiable. Unfortunately, we cannot understand from the decision if the fact that it was cited as a preferred HMG CoA reductase inhibitors was a decisive factor.
Concerning the second test, does the association A (Ezetimib) and B (Simvastatin) necessarily fall under the invention covered by that patent, that is to say, does it embody the technical contribution made by the patent?
The judge explains that « the patent further indicates (page 6, lines 21 of its description) that the invention also relates to a method of reducing plasma cholesterol levels, and to a method of treating or preventing atherosclerosis, comprising administering, to a mammal in need of such treatment, an effective amount of a combination of a substituted hydroxy azetidinone as a cholesterol absorption inhibitor of formula I and a cholesterol biosynthesis inhibitor”[4].
The judge concludes that the invention derives from the basic patent in force, within the meaning of Article 3 (a) of Regulation (EC) No 469/2009, includes, in addition to hydroxy substituted azetidinone compounds as hypocholesterolemic agents alone (Ezetimib alone), the combination of these active ingredients, including Ezetimibe, with Simvastatin. Therefore, there are two technical contributions in this patent: Ezetimibe alone and “Ezetimibe + Simvastatin”.
This french decision granted an SPC following the new guidelines of the ECJ one month after a British decision[5] refused to grant an SPC based on the same rules. In this British decision, the facts were different since the judge correctly considered that the second active ingredient of the combination was not specifically identifiable, it was not mentioned in the patent, it was not even a member of a specific class of compounds mentioned in the patent, whether by reference to their structure or activity, as being suitable for combination with the compounds of the invention…
To conclude, the new guidelines coming from the decision C 121/17 seems the clearest rules ever coming from ECJ, but of course, they are still subject to interpretation and therefore, member states would still render divergent decisions.
Resource List:
[1] European Court of Justice (ECJ); Teva UK Ltd, Accord Healthcare Ltd, Lupin Ltd, Lupin (Europe) Ltd, Generics (UK) trading as ‘Mylan’ v Gilead Sciences Inc, C 121/17, 25 July 2018 (Darts-ip reference: darts-378-846-F-en)
[2] Eng & Wales High Court C.Div, Teva UK Ltd, Accord Healthcare Ltd, Lupin Ltd, Lupin (Europe) Ltd, Generics (UK) trading as ‘Mylan’ v Gilead Sciences Inc, uk-2017-ewhc-13-pat, 13 January 2017 (Darts-ip reference: darts-712-373-D-en)
[3] In the light of the description and drawings of that patent.
[4] The description adds that in another aspect, the invention relates to an effective pharmaceutical composition of a substituted hydroxy azetidinone as a cholesterol absorption inhibitor as Ezetimib, a cholesterol biosynthesis inhibitor and a pharmaceutically acceptable carrier.
[5] Eng & Wales High Court C.Div, Teva UK Ltd, Accord Healthcare Ltd, Lupin Ltd, Lupin (Europe) Ltd, Generics (UK) trading as ‘Mylan’ v Gilead Sciences Inc, uk-2018-ewhc-2416-pat, 18 September 2019 (Darts-ip reference: darts-596-717-F-en.)
