Ezetimibe & Simvastatin – France

 

On Sep 25, 2020, Court of appeal of Paris found SPC for combination of ezetimibe & simvastatin product invalid.

Background:

Merck owns European Patent No. 0720599 (EP 599) entitled "Hydroxy-substituted azetidinone compounds effective as hypocholesterolemic agent” which is expired on September 14, 2014. It claims novel compound ie. Ezetimibe and also combination with other agents such as cholesterol biosynthesis inhibitor for the treatment of atherosclerosis. Specifically, dependent claims 9 to 18 claim the combination which cover simvastatin among other inhibitors. Merck granted first SPC (n°03C0028 – expired on April 17, 2018) on this basic patent which covers single ezetimibe product, EZETROL.  Merck also obtained second SPC (n°05C0040 – expired on April 2, 2019) on the same patent which covers ezetimibe & simvastatin combination product, INEGY.

Teva launched generic version of EZETROL  on April 18, 2018 and of INEGY on April 24, 2018 & requested invalidity of claims 9 to 18 of EP’599 patent and of the SPC No. 040 before court. Tribunal de Grande Instance of Paris court rejected Teva’s request & ordered Teva to pay the cost and to pay Merck the sum of 100,000 euros. Teva appealed.

Appeal courts analysis:

Article 3 of Regulation (EC) No 469/2009: SPC shall be granted if –

(a) the product is protected by a basic patent in force;

(b) a valid authorisation to place the product on the market as a medicinal product has been granted in accordance with Directive 2001/83/EC or Directive 2001/82/EC, as appropriate;

(c) the product has not already been the subject of a certificate;

(d) the authorisation referred to in point (b) is the first authorisation to place the product on the market as a medicinal product.

Court said that aforementioned articles of the Regulation must be interpreted in the light of the case law of the CJEU, in particular with regard to the Sanofi C 443/12 (Irbesartan + HCTZ) decision dated December 12, 2013, which deals with similar facts. Merck argued that this Sanofi case law is not applicable to the case at hand in that the product in question concerned the combination of irbesartan with HCTZ (hydrochlorothiazide) and that the patent did not contain a claim expressly mentioning HCTZ.  Here, in present case, claim 17 specifically mentions simvastatin and thus it is protected. The Court said that the CJEU, in its Sanofi decision, held that even if the condition laid down in Article 3(a) of Regulation No 469/2009 were satisfied, for the purpose of the application of Article 3(c) of that regulation, it cannot be accepted that the holder of a basic patent in force may obtain a new SPC, each time he places a product on the market. Court further said that Person skilled in the art after reading the patent specification would not assume this combination as “distinct product”. The description of the patent, which uses the singular to designate the invention, and uses the formula "in yet another aspect" to present the combination of a hydroxy-substituted azetidinone, object of the invention, with a cholesterol biosynthesis inhibitor, refers indifferently for hydroxy-substituted azetidinones alone and for their combination with a cholesterol biosynthesis inhibitor.

In the present proceeding, as in the Sanofi case, the EP 599 patent protecting the active ingredient in particular ezetimibe, has already led to the grant of a SPC on this active ingredient to its holder, and this first SPC relating to ezetimibe alone allowed Merck to oppose to the marketing of a drug containing ezetimibe in combination with a statin such as simvastatin and having a therapeutic indication similar to that of the drug Ezetrol. Thus, the supplementary protection certificate FR05C0040 is null and void.

Parallel proceedings related to this SPC:

France: On Feb 14, 2020 this appellate court reversed the decision of preliminary injunction granted against Sandoz & Mylan.

Norway: On December 21, 2018, Borgarting Court of Appeals affirmed lower court decision which granted preliminary injunction.

Czech Republic: On August 28, 2018, Prague Court of Justice issued preliminary injunction.

Portugal: On September 7, 2018, Portuguese Arbitral Tribunal issued preliminary injunction.

Belgium: On December 21, 2018, Commercial Court of Brussels issued preliminary injunction.

Austria: On July 10, 2019, Vienna Court of Appeals affirmed preliminary injunction.

Netherlands:  On October 23, 2018, Court of Appeal of The Hague affirmed & held SPC invalid.

Germany:  On March 15, 2019, Court of Appeal of Düsseldorf affirmed & held SPC invalid.

Spain:  On September 12, 2018, Regional Court of Barcelona found SPC invalid.