Escitalopram: product claims invalid, SPC upheld

Recently, the Court of Appeal (Hof) at The Hague ruled on the validity of Lundbeck's patent on the antidepressant Escitalopram. The ruling is remarkably different from that in several other countries, particularly in denying the patentability of the product claims.

In order to understand the matter, one should realise that many drug substances exist in two different forms which are called enantiomers, generally denoted as S and R forms. Without special synthesis or separation methods, the drug will be a so-called racemic mixture, consisting of both forms in equal amounts. Escitalopram is based on the S-enantiomer of citalopram, which pre-existed as a racemic mixture. Claimed were S-citalopram per se, and a method of making it via a defined precursor.

The individualised S-enantiomer was found novel in accordance with standard case law. As to inventive step, the patentee argued that S-citalopram amounted to an inventive selection from within a large group of antidepressant drugs. The Court, however, considered it had been common practice to study the effects of individual enantiomers in a racemic drug. The relevant starting point for the skilled person would therefore have been racemic citalopram. To then arrive at a selection of the more active of the two enantiomers did not entail an inventive step.

Finding the process claim patentable, the Court acknowledged that in other jurisdictions this had played a role in supporting the patentability of the product claims. Reference was made to decision T595/90 of the Technical Board of Appeal at the EPO. This decision indicates that a product defined by an obvious characteristic could still be patentable if no suitable way existed in the art to make the product as defined. However, in the case of a racemic mixture, separation techniques did exist, and thus the present case did not satisfy the patentability requirements of T595/90.

The Court did not stop at this, but opined on "proportionality", confirming that in its view a patent monopoly should be commensurate with the technical contribution to the art. The invention being a method to make S-citalopram, the protection is for the method, and for the product directly obtained from it. The patentee's contribution to the art did not relate to S-citalopram per se.

The Court pointed out that where in other jurisdictions the product claims were held patentable, this was expressly in the absence of any discussion on proportionality. The Court added that proportionality was discussed in the UK, but only vis-à-vis the reproducibility of the invention. The UK court did not opine on the situation at hand: that of a novel, yet not inventive substance that is produced by a novel and inventive process.

The Dutch Court also ruled on the supplementary protection certificate (SPC) for Escitalopram. Two main arguments were raised against the SPC. One directly related to the fact that the patent had become limited to the process, whilst the SPC had been issued for the product. The Court confirmed that a process patent may form a basis for an SPC, and that the product resulting from the process is protected by the patent as well. Accordingly, the SPC issued for the product could still be considered to be within the limits of the patent relied on. The other argument was based on the pre-existing market authorisation for citalopram. Since the racemic mixture by definition contained the S-enantiomer, the marketing authorisation for Escitalopram would not have been the first one for this product, as is required for obtaining an SPC. Particularly, it had been argued that almost the entire activity of citalopram resided in the S-enantiomer. It was also pointed out that, precisely for this reason, the Dutch Medicines Evaluation Board did not accord to Escitalopram the status of "new active substance". The Court, however, reasoned that the term "product" in the legislation on SPCs should be read as relating to an active substance in the narrow sense as understood in patent law. Accordingly, since S-citalopram was novel over citalopram, it by definition counted as a different product under SPC legislation.

Hajo Kraak