Daiichi owned a patent concerning levofloxacin, an enantiomer of the racemic mixture, ofloxacin. Daiichi also owned a Supplementary Protection Certificate (SPC), based on the patent and the marketing authorisation it had obtained for levofloxacin. Generics UK claimed that the patent was invalid over ofloxacin, as it was obvious that the enantiomers of a racemate are likely to have different properties in vivo. It also claimed that the SPC was wrongly granted because it was not based on the first marketing authorisation for the product, namely the earlier marketing authorisation that had been obtained for the racemate (which contains levofloxacin). Rather it had been granted on the basis of the later authorisation for levofloxacin. The judge found both the patent and SPC valid.

Background

The defendants (Daiichi Pharmaceutical Co. Ltd and Daiichi Sankyo Co. Ltd) owned a patent which disclosed levofloxacin, an S(-) enantiomer of the racemate ofloxacin. Levofloxacin had proved to be a superior anti-microbial than ofloxacin or the R(+) enantiomer. A marketing authorisation was granted for levofloxacin and the defendants obtained an SPC based on this and the patent. The patent had expired but the SPC was still in force.

The claimant (Generics (UK) Ltd) sought to knock out the SPC on the grounds that (i) the patent was invalid over ofloxacin and further or alternatively (ii) the SPC was wrongly granted because it was not based as it should have been on the first marketing authorisation, namely the earlier marketing authorisation for the racemate, ofloxacin (which contains levofloxacin).

According to the SPC Regulation (EEC/1768/92), an SPC shall be granted if (a) the active ingredient or a combination of active ingredients (the "Product") is protected by a patent in force, (b) there is a valid marketing authorisation for that Product to be sold as a medicinal product, (c) the Product has not already been the subject of an SPC and (d) the said authorisation is the first authorisation to sell the Product as a medicinal product. The claimant argued that condition (d) was not met.

Outcome

Validity of the patent

The patent was held valid over ofloxacin. This was despite finding that the skilled person would appreciate that ofloxacin was a racemate, and that one enantiomer might have better activity (in terms of both safety and efficacy) than the other or the racemate, as the claimant's experts contended. The judge placed weight on the defendants' expert's evidence that his team and other researchers perceived there to be great potential in discovering new chemical entities in a class of anti-microbial agents called quinolones. Ofloxacin was a member of this class. Further, the defendants' expert asserted that there was uncertainty as to whether the enantiomers of quinolones would produce a better compound than the racemate. Accordingly, it was his view that the resolution of racemates was not really on the radar of researchers in this area.

As neither of the claimant's experts was working in the field of quinolones at the relevant date, and their view was inconsistent with the lack of stereochemistry coverage in major review articles, the judge was led to conclude that it would be obvious to try to resolve ofloxacin into enantiomers only if it were relatively easy to do so. If not, the skilled person would redirect his efforts into finding new compounds, in light of the "unusual" nature of the quinolone field. Unfortunately for the claimant, its experiments showed that it was difficult to resolve the ofloxacin into its enantiomers, and the work up of the experiments was not shown to be available at the relevant time. The judge instead agreed with the defendants that the resolution of racemates was a bit of a "black art".

The judge found the patent to be inventive over all other pieces of prior art, after applying the steps set out in the Pozzoli case. Interestingly, the claimant sought to rely on common general knowledge at the priority date, combined with a poster which was displayed for only two hours, three years beforehand. The defendants submitted that this combination of information could not be relied upon because it would never have occurred in reality. They submitted that those who had read the poster would have forgotten about it by the priority date. However, the judge held that such a combination is permissible, since once the information is made available, it cannot be withdrawn. Indeed, the European Patent Convention is drafted to encompass anything which has been disclosed as being in the "state of the art".

SPC application

The crucial question was whether the first marketing authorisation for the Product (i.e. levofloxacin) was the earlier authorisation for the racemate, ofloxacin (which contains levofloxacin) or the later authorisation for the single enantiomer, levofloxacin. Since the R(+) enantiomer also has an anti-microbial activity, the judge found that ofloxacin was itself a product, being a combination of two active ingredients (levofloxacin and the R(+) enantiomer) with an anti-microbial activity. Therefore, ofloxacin was a different product to levofloxacin. Hence, the judge found that the first marketing authorisation for levofloxacin was that for the single enantiomer and not the racemate. In making this judgment, the judge reiterated the object of the SPC Regulation, namely to provide an effective period of protection for research centres developing new medicinal products.

Comment

Against the backdrop of a number of recent European-wide negative decisions in which the validity of an SPC was in contention, this rare victory will be welcomed warmly by research-based pharmaceutical companies.

On finding the patent was not obvious this was another case, following the Lundbeck case, in which an enantiomer of a known product was found to be inventive. Both sides' experts were found to be independent and to have given considered views, which made this case a close call. However, the defendants' experts had more relevant experience, being researchers in the field of quinolones. That may have tipped the decision in favour of the defendants. The defendants were then helped by the claimant's failure to demonstrate that the resolution of ofloxacin was relatively easy. Unlike Lundbeck, the defendants were not even required to show that the resolution of the racemate was not obvious.