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September 2009


unreasonable in terms of the tests and analyses the skilled person would conduct, whereas the UK court considered this to extend the CGK too far.


What impact might this divergence in application of patent law between territories have? Are the UK courts more supportive of innovators, are the German Courts pro- generic? If there was a European Court to consider the matter overall, which decision would have been applied?


Levofloxacin, 2008 [17] (the (-)-enantiomer of ofloxacin, amember of the quinolone class of anti-microbial agents)


The rejection of the insufficiency attack by the Court of Appeal in escitalopram was acknowledged, as were the findings of the Judge himself in that case on novelty. The patent expired in June 2006 but an SPC existed to protect levofloxacin (Fig. 3) until June 2011. The SPC’s validity was challenged in two ways: 1) the patent was invalid and 2) the SPC should not have been granted.


the other beneficial qualities of the racemate…[H]e would have considered it worthwhile exploring whether ofloxacin could be resolved, but only to a point.” The Judge did not believe it was a goal obvious to pursue relentlessly.


The Judge was not persuaded that the skilled person would have achieved separation of the diastereomers by preparative HPLC in 1985. Chiral separation would have involved a research programme with an uncertain outcome and in the Judge’s opinion, the person skilled in the art would have turned his attention to development of new molecules if the enantiomers could not be separated relatively easily.


For an SPC to be valid, itmust be for a product which has not already been subject to a certificate and be based on the first marketing authorisation to place the product on themarket as amedicinal product. The argument advanced was that the authorisation to sell ofloxacin was the first to sell levofloxacin because it is an active component of ofloxacin. The Judge rejected this.


Figure 3 levofloxacin (commonly prepared as its hemihydrate)


Preparative HPLC experiments were relied on to demonstrate that chiral separation could have been achieved but it was not possible to show that the equipment used was available, let alone CGK in 1985. Although the same outcome may well have been achieved on this equipment, proving it is problematic.


The Judge concluded: “by 1985 the skilled person would have been aware of the particular promise of ofloxacin as a pharmaceutical and its chiral nature. It was possible one enantiomer might have more activity than the other and…would retain


The Court of Appeal [18] noted that from all practical points of view and that of patent law, levofloxacin was a new product, and the earlier authorisations did not entitle Daiichi to market it as such. Once the ofloxacin patent expired anyone could market ofloxacin; levofloxacin could not be marketed due to the levofloxacin patent and prior to this no-one could market it because invention was needed to make it.


The authorisation for levofloxacin was the first for that active ingredient alone. One Judge remarked that the position might have been different if the other component of the racemic mixture had been inactive biologically but it was a moot point.


Conclusion


Not only can a single enantiomer of a known racemate be entitled to 20 years patent protection, it can also be protected for a further 5 years by an SPC.


It can be seen that when patent law is strictly applied to the facts where chiral separations are concerned, many policy issues arise as to


what is the appropriate scope of protection for “inventions” of this type. It is evident that, even though patent law is supposed to be the same throughout Europe, Courts in different jurisdictions consider chiral separations differently which can lead to conflicting outcomes.


A point of note is how important publications of chiral separations are to patent litigation. One problemwhich lawyers and expert witnesses face is where subjectmatter has been considered too obvious to be published! Without publications to support expert opinion on what was CGK at the relevant time, it can be difficult to prove that separation could ‘easily’ be achieved in instances when it, in fact, was.


References [1] Prior art, or state of the art, constitutes all information that has been made available to the public in any form before the priority date5


[2] Beloit Technologies Inc v Valmet PaperMachinery [1997] RPC 489


[3] Genentech Inc’s patent [1989] RPC 147 [4] Ranbaxy UK Ltd vWarner-Lambert Co [2006] FSR 14 [5] The priority date is the date at which a patent application is filed. It is the cut-off point for determining what is included in the ‘state of the art’ against which the novelty or inventive step of the claimed patent is assessed.


[6] Generics (UK) Limited & Ors v H. Lundbeck A/S [2007] RPC 32


[7] Merrell Dow Inc v H.N.Norton & Co. Ltd [1996] RPC 76 [8] T1046/97 & T0296/87 (Technical Board of Appeal) [9] Biogen Inc vMedeva Plc [1997] RPC 1 [10] H.Lundbeck A/S v Generics (UK) Limited & Ors [2008] EWCA Civ 311


[11] Generics (UK) Limited & Ors v H. Lundbeck A/S [2009] EWHL 12


[12] Neolab Ltd & Ors v H.Lundbeck A/S (Ni 352 Federal Patent Court)


[13] Cf. BGH GRUR 1978, 696, 698 – Aminobenzylpenicillin; BPatG [Federal Patent Court] GRUR Int. 1996, 822 – Herbicid wirksames Enantiomer


[14] I.W.Wainer, Trends in Analytical Chemistry 6 (1987) 125-134 [15] D.Haupt, J. Chromatography B, 685 (1996) 299-305 [16] B.Rochat et al, Ther.Drug.Monit. 17 (1995) 273-279 / B.Rochat et al, Chirality 7 (1995) 389-395


[17] Generics (UK) Limited v Daiichi Pharmaceutical Co. Ltd & Daiichi Sankyo Co Ltd [2008] EWHC 2413


[18] Generics (UK) Limited v Daiichi Pharmaceutical Co. Ltd & Daiichi Sankyo Co Ltd [2009] EWCA Civ 646


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