INNsight articles by Duncan Curley

“Incremental innovation” is a phrase that is often used to cast aspersions on the research-based pharmaceutical industry for carrying out routine chemistry in order to derive new drug products.  There is ongoing debate about whether the results of this kind of research should be protected by patents.  For example, it has long been established that the stereochemistry of a small molecule API is usually important, insofar as biological activity is concerned.  What technical contribution can there be in isolating the optically active form of a drug that has been used for many years as a racemate (a mixture of (+) and (-) enantiomers)?  

The selective serotonin reuptake inhibitor (SSRI) citalopram has been sold as a racemate in the UK for many years, originally as the branded product Cipramil®.  A number of SSRIs are big products for the pharmaceutical industry.  The patent for citalopram expired several years ago, but the patentee, H. Lundbeck A/S, managed to obtain European Patent 0347066 B1 for “New enantiomers and their isolation”.  Claim 1 is to the compound (+) citalopram (escitalopram), per se.  Claim 3 is to a pharmaceutical composition comprising escitalopram as an active ingredient.  Claim 6 is to a specific method of preparation of escitalopram, involving a stereoselective synthesis from an optically pure intermediate.  

The validity of these claims has been challenged in the UK by three generic companies: Generics [UK], Arrow Generics and Teva.  The respected Patents Court Judge, Kitchin, J., had at first instance found Claim 6 (the process claim) valid but Claims 1 and 3 invalid.  However, as reported on GenericsWeb last year, the legal ground upon which the Judge based his findings of invalidity was unusual - insufficiency.  Insufficiency is usually deployed as a reason for invalidating a patent either when there are technical deficiencies with the language in the specification (that prevent the skilled reader from understanding how the invention should be put into practice), or when the claims do not make the scope of the monopoly sufficiently clear.  The invention disclosed in Lundbeck’s patent was quite simple to understand and it was clearly and completely described.  Why then did the Judge come to the conclusion that the escitalopram product claims were bad for insufficiency?  

The reason was as follows.  By the priority date of the patent (1988), noone else had resolved citalopram into its constituent enantiomers.  The Judge was nevertheless satisfied that citalopram was an obvious target for resolution prior to this date: purified (+) citalopram – the single enantiomer, escitalopram - was an “obvious desideratum”.  The Judge held that Lundbeck’s technical contribution was to develop a process for the synthesis of optically pure escitalopram.  Yet the product claims in the patent give Lundbeck a complete monopoly on escitalopram, whether made by the route of synthesis developed by Lundbeck or whether obtained by any other method (the one cited in the case was preparative HPLC).  The Judge had therefore held that Lundbeck’s product claims to escitalopram were too broad.  They gave Lundbeck a monopoly that extended beyond Lundbeck’s technical contribution to the art (or, put another way, the claims were not commensurate with Lundbeck’s technical contribution).  This was similar to the way in which the House of Lords had formulated a ground of insufficiency in their decision in Biogen v Medeva (a case involving recombinant DNA technology). 

On appeal, Lundbeck mounted an attack on the Judge’s findings of Biogen insufficiency in relation to the two product claims.  Lord Hoffmann, who normally sits in the House of Lords (and who gave the main opinion in the Biogen case), sat on the panel of three Court of Appeal judges and gave the leading judgment. 

The Court of Appeal overturned the Judge’s decision.  It held that a product claim is sufficiently enabled (i.e. it is sufficient) if the patent specification enables the skilled person to make the product in question.  Furthermore, all the patentee has to do is to provide one method of synthesis in order to maintain a monopoly claim to the product itself.  Lord Hoffmann observed that this was consistent with the practice in the European Patent Office.  He distinguished the previous decision in Biogen by saying that it was made on the basis of the particular form of the claim that was in issue in that case.  

Although the generic companies had cross appeals on the issues of novelty and obviousness (they had lost on those points at first instance), these appeals failed.  Lundbeck’s appeal was therefore successful and the two all-important product claims to escitalopram are therefore valid, giving Lundbeck an effective monopoly on the product in the UK until 31 May 2014, when the SPC for escitalopram oxalate expires.