Generics (UK) Limited (“GUK”) was unsuccessful in its attempt before the Patents Court (Mr Justice Kitchin) to revoke Daiichi’s Supplementary Protection Certificate (“SPC”) in respect of levofloxacin. Levofloxacin is the (-) enantiomer of the racemic antimicrobial ofloxacin. GUK made a two-pronged assault on the SPC. First on the basis that there were grounds which would have justified revocation of the underlying patent EP(UK) 0206283 (“the patent”). The patent claimed the product levofloxacin (claim 2) and the method of making levofloxacin (claim 5). GUK made various challenges to these claims including on the grounds of lack of novelty and inventive step. The second separate attack was founded on the prior marketing authorisations for ofloxacin.
GUK challenged the priority date of the patent on the basis that the first priority document referred to the two fold increase in activity of levofloxacin compared to the racemate, but did not include any of the toxicity or solubility data included in the third priority filing.
The judge emphasised the importance of making a distinction between the priority dates of the claimed invention and that of matter contained in an application. The invention is entitled to the priority date of an earlier application when the invention is supported by matter disclosed in such earlier application (applying Asahi Kasei Kogyo Application ( RPC 485 and G02/98, Same Invention ( OJ EPO 413). On the facts the judge held that the invention of each of the claims in issue was plainly disclosed by the first priority document. The priority document enabled the skilled person to perform the inventions claimed without undue difficulty.
The judge went on to point out that Daiichi were not permitted to rely on the subsequently added toxicity and solubility information in support of its obviousness defence. As previously stated by the judge in Generics v Lundbeck ( EWHC 1040) a patentee may not rely on a discovery which was neither made at the date of the priority document nor could be predicted from such document’s contents.
GUK also contended that prior publication by Daiichi of the racemate ofloxacin rendered the claimed enantiomer old. The judge (applying Synthon v SmithKline Beecham ( UKHL 59) rejected this argument. Performance of the subject matter of the prior art would result in the production of ofloxacin which does not constitute an infringement of a claim to levofloxacin. The prior art contained nothing which enabled or even pointed towards the resolution of ofloxacin into its constituent enantiomers. The judge referred to the judgment of the Court of Appeal in Lundbeck v Generics UK Ltd ( EWCA Civ 311) where Lord Hoffman approved the settled EPO case law that the prior disclosure of a racemate did not in itself amount to a disclosure of its enantiomers.
With regard to the attacks on inventive step, it was argued that both claims 2 and 5 were obvious. The judge cited the approach to determining obviousness in Pozzoli v BDMO ( EWCA Civ 588). He also pointed out that the Court of Appeal in Conor v Angiotech ( UKHL 49) had expressly approved his approach to the question of obviousness in Generics v Lundbeck.
GUK argued that it was obvious to seek to resolve the enantiomers of ofloxacin. The judge decided on the evidence that while the resolution of ofloxacin would have been something worthwhile to explore, it was not a goal which was obvious to pursue relentlessly. It was only obvious to investigate whether the resolution could be achieved easily, but if it could not the skilled person would not have continued to pursue this line of research.
GUK also alleged that the method for carrying out the separation was obvious. GUK sought to establish obviousness by performing experiments purporting to show obvious ways in which the skilled person could have resolved ofloxacin at the priority date. However, a reproducible, scaleable resolution was not achieved with the conditions attempted. Daiichi levelled a number of criticisms at GUK’s experiments. Those criticisms which the judge found particularly persuasive were firstly in relation to the diastereomeric salts approach: GUK’s expert did not ‘select’ the successful resolving agent himself, but rather the answer was ‘put under his nose’ by GUK’s solicitors. In addition the preparative HPLC experimental team optimised their approach on modern equipment and then attempted to replicate the optimised method on modern versions of apparatus available at the priority date. The dangers of allowing hindsight to affect the design of experiments intended to prove obviousness are apparent from this case.
The judge accepted that there were a number of possible methods available to persons seeking to resolve a racemate at the priority date. The evidence was that such methods break down into an almost infinite number of permutations, such that no resolution was simple and there was no guarantee of success. Applying the law to the facts, the judge held that there was no evidence based on any of the publications in evidence and the common general knowledge that either the claimed product or the process claim were obvious. The judgment keenly illustrates the uphill struggle faced to present a successful obviousness case in the light of experiments which fail to achieve the purportedly obvious.
The SPC Regulation (No 1768/92) was enacted in recognition of the fact that the time period between applying for a patent and obtaining authorisation to put a new medicinal product on the market rendered the monopoly granted under the patent too short to encourage the development of medicinal products.
The SPC Regulation confers, by means of a Supplementary Protection Certificate (SPC), post patent expiry “patent like” protection on products protected by a basic patent, for which there is a marketing authorisation. Such product must not have already been the subject of an earlier authorisation or SPC in the country in which it is sought. The duration of protection is a maximum of 15 years from the date of first authorisation in the Community, including the life of the basic patent (or 5 years from patent expiry, whichever is the shorter). For the purpose of the Regulation a ‘product’ is defined as the active ingredient or combination of active ingredients of a medicinal product.
GUK brought two challenges against the SPC. The first was that the 6 June 1997 UK marketing authorisation for levofloxacin was not its first UK marketing authorisation. GUK contended that the 1990 marketing authorisation for ofloxacin was in fact the first UK marketing authorisation for levofloxacin because levofloxacin was present in the racemate in a 50:50 mixture with the (+) enantiomer. The second was that the reference point for the 15 year maximum period of protection conferred by the SPC was the first authorisation in the Community and was the marketing authorisation for ofloxacin that had been granted in Germany in 1985. GUK argued therefore that the term of the SPC granted to Daiichi in 1997 should have been zero.
GUK’s challenge to the SPC is of particular interest because despite the many cases concerning the resolution of enantiomers, this is the first time this particular argument has been brought before the courts. There are many enantiomer products on the market in the same position as levofloxacin, where the duration of the SPC protection was determined from the date of the marketing authorisation for the enantiomer and not the prior marketing authorisation for the racemate.
The judge set out the policy considerations behind the institution of the SPC Regulation. He then reviewed the UK and European Court of Justice jurisprudence on the point. BASF AG v Bureau Voor De Industriele Eigendom ( RPC 9) is a case concerning products within the meaning of the Plant Protection Products Regulation No. 1610/96 and that in many respects parallels that for medicinal products here in issue. In BASF it was held that two products which differ only in the proportion of the active chemical compound to the impurity they contain must be regarded as the same product. The fact that a new marketing authorisation must be obtained for plant protection products with different quantities of impurities is irrelevant. Another case, Massachusetts Institute of Technology ( FSR 34) determined that an ingredient of a medicinal product cannot constitute a “product” for the purposes of the Regulation unless it has an effect on the human or animal body on its own.
The judge viewed the fundamental question to be “whether or not the product the subject of the 1985 and 1990 authorisations was ofloxacin or levofloxacin”. He concluded that the marketing authorisation for ofloxacin did not amount to the first authorisation to place levofloxacin on the market.
He reasoned that ofloxacin was in itself a recognised as a good antimicrobial. Its properties had been determined and until the invention of the patent the characteristics of the enantiomers were unknown. Therefore the marketing authorisation for ofloxacin was just that, permission to place the named active ingredient ofloxacin on the market and not levofloxacin. He went on to say that it is now known that each of the racemate and the two enantiomers have different properties. The (+) enantiomer is not inactive; it has antimicrobial properties in its own right. Therefore ofloxacin is either an active ingredient in its own right or a combination of active ingredients. The (+) enantiomer is not an inactive impurity as in BASF or an excipient as in MIT. To this extent his reasoning does not necessarily close the door on similar challenges to single enantiomer products where it has been determined that the biological activity of the racemate resides only in one enantiomer. It is unclear from the judge’s reasoning what the outcome would have been had the (+) enantiomer not exhibited biological activity.
In further support of his findings, GUK had accepted that ofloxacin does not fall within the scope of the patent. The judge’s decision would not for that reason cause undue extension of the protection for ofloxacin.
As Mr Justice Kitchin himself concluded, this decision is consistent with the policy reasons for the SPC Regulation in the first place. It required invention to make levofloxacin. The application for the Patent was filed in 1986 but authorisation to place levofloxacin the market as a medicinal product was not granted until some 11 years later, in 1997. Mr Justice Kitchin pointed out that if GUK’s SPC challenge had been successful Daiichi would have had only nine years of protection from the date of the authorisation to the date of expiry of the Patent, and this is precisely the vice at which the SPC Regulation is aimed