On 17 September 2012, the Court of Appeal of Brussels (the “Court”) confirmed the validity of the patent and supplementary protection certificate (“SPC”) in escitalopram, an active substance of the pharmaceutical product marketed by Lundbeck H. A/S under the trade name Sipralexa®. The Court thereby overturned the judgment of the commercial court of Brussels of 3 October 2011 (See, this Newsletter, Volume 2011, No. 10, p. 11) and imposed an injunction against the generic companies that had claimed the invalidity of the SPC and had marketed generic versions of escitalopram.
Before it started selling Sipralexa®, Lundbeck already commercialised another antidepressant, namely Cipramil®. Cipramil®, which is still available on the market, is based on the active ingredient citalopram which is a so-called ‘racemate’. A racemate is a mixture of two enantiomers (an S-enantiomer and an R-enantiomer), i.e. two molecules that are each other’s mirror images and that are not identical. Lundbeck received the marketing authorisation for Belgium for Cipramil® in May 1990. Citalopram was protected by a Belgian patent that expired in January 1997. The patent protection of citalopram was prolonged by a SPC that expired in January 2002. Sipralexa®, on the other hand, is based on the active ingredient escitalopram which is the S-enantiomer of citalopram. The marketing authorisation for Belgium for Sipralexa® was granted in July 2002. Escitalopram was protected by a European patent that expired in June 2009. An SPC for escitalopram (the “Sipralexa SPC”) expires in June 2014.
A number of companies, including Eurogenerics, Ratiopharm, Teva Pharma Belgium and Tiefenbacker (the “Generic Companies”), sought to put on the market a generic pharmaceutical on the basis of escitalopram. However, such a product could not be launched as long as escitalopram is protected by the Sipralexa SPC. In 2008, Ratiopharm and Tiefenbacker summoned Lundbeck to appear before the Court claiming that the Sipralexa SPC should be declared invalid. Later, Teva and Eurogenerics joined the proceedings.
The Generic Companies claimed that the Sipralexa SPC is invalid for a number of reasons. In particular, they contended that the SPC is invalid because (i) the underlying patent for escitalopram is invalid; (ii) an earlier SPC had been granted for the same product, namely the SPC for citalopram or marketing authorisation; and (iii) the Sipralexa SPC is contrary to the ratio of Regulation No 469/2009 of 6 May 2009 concerning the supplementary protection certificate for medicinal products (the “SPC Regulation”).
Issues of Patent Validity
The Generic Companies claimed that the SPC should be invalidated on the basis of the invalidity of the underlying patent for escitalopram (Article 15.1 sub c) of the SPC Regulation).
Thus, the Court was requested to analyse the validity of the escitalopram patent. In its analysis of the patent, the Court first held that the product as well as the method for obtaining this product disclosed in the escitalopram patent were new in view of the prior art at the filing date. According to the Court, the Generic Companies failed to prove that the prior art unambiguously disclosed the S-enantiomer of citalopram or the method by which it was obtained.
Second, on the inventive step required for patent protection, the Court adopted the ‘problem and solution approach’ applied by the European Patent Office (“EPO”). When defining the objective technical problem, the Court refused the definition suggested by the Generic Companies, i.e., that the invention sought to find a method to divide citalopram into its enantiomers, since this definition already implies part of the solution. Instead, the Court maintained that the problem at hand was finding an improved antidepressant or one with effects at least comparable to citalopram.
Based on this definition of the objective technical problem and taking account of the state of the art at the time of filing for the patent, the Court assessed the inventive step. Referring to the case law of the Board of Appeal of EPO, the Court explained that it is not the question whether the skilled person could have carried out the invention but whether he would have done so in the hope of solving the underlying technical problem or in the expectation of some improvement or advantage (the so-called “could-would approach”). A number of elements furthermore pointed to the existence of an inventive step. In particular, there is an inventive step if (i) there is only a limited degree of “reasonable expectation of success”; (ii) the invention results in an unexpected effect; (iii) the skilled person would be deterred from the invention; or (iv) there is an “undue burden” to reach the invention.
In the case of Lundbeck’s patent, the Court held that the general reasons mentioned by the Generic Companies for researching enantiomers do not suffice to find an absence of inventive step. Instead, based on expert reports, the Court found that a number of elements would have deterred the skilled person from applying this general guidance on citalopram to obtain escitalopram. Accordingly, the Court confirmed the validity of the escitalopram patent.
SPC not invalidated based on earlier SPC
The Generic Companies argued that the Sipralexa SPC was invalid since an earlier SPC had been granted for the same product (Article 15, 1, sub a) and Article 3, sub c) of the SPC Regulation).
The decision of the Court on this argument turned on the assessment whether escitalopram and citalopram are the same “product”. The Court held that the Generic Companies had to show that escitalopram was the only active ingredient in citalopram and is therefore the only ingredient that can establish the pharmacological, immunological or metabolic effect to restore, improve or alter physiological functions. Referring to the ECJ judgment in the MIT Case (C-431/04) and the preparatory works of the SPC Regulation, the Court held that a strict identity between the products is required and concluded that this was not demonstrated for the products at hand. In particular, it was not established that the R-enantiomer is completely inert and does not contribute to the functioning of the racemate citalopram as an antidepressant.
In a similar vein, the Generic Companies argued that the Sipralexa SPC should be invalidated because an earlier marketing authorisation had been granted for the same product (Article 15.1 sub a) and Article 3, sub d) of the SPC Regulation). This argument was equally dismissed by the Court based on its finding that Sipralexa® and Citalopram® are different products.
Ratio of the SPC Regulation
Finally, the Court refused to invalidate the Sipralexa SPC on the grounds that the SPC is supposedly contrary to the ratio of the SPC Regulation. The Court held that there was no legal text providing for the invalidity for this reason and, even if there were such a ground, the position that escitalopram and citalopram are two different products is not contrary to the purpose of the SPC Regulation.
As a result, the Court confirmed the validity of the Sipralexa SPC and imposed an injunction on the Generic Companies prohibiting any generic products containing escitalopram.
