The High Court found that the a patent for a drug used to treat hypertension was infringed by Apotex’s generic equivalent. However, due to the disclosure in an earlier patent (also owned by the claimants) for the industrial synthesis of the same drug, the patent was invalid for lack of both novelty and inventive step. The amendments sought by the patentee were not be allowed and the patent was revoked in its entirety.
The claimants were the French company Les Laboratoires Servier and an exclusive licensee, its wholly owned English subsidiary (Servier). The defendants, Apotex, were a Canadian group of companies concerned with the manufacture of generic pharmaceuticals. Servier’s European process patent for the alpha crystalline form of the drug perindopril had a priority date of 6 July 2000. The original patent for the compound itself expired on 21 June 2003. Perindopril is used in the treatment of hypertension (high blood pressure).
In March 2006 Servier learnt of Apotex’s intention to launch perindopril in Europe (planned for June that year). On 26 July 2006 Servier issued proceedings for infringement of the patent. Apotex counterclaimed for invalidity. Their patent having survived an opposition at the European Patent Office, Servier learnt that Apotex intended to launch its generic product immediately. Consequently, Servier applied for, and was granted, an interim injunction by Mann J on 8 August 2006. The perindopril market was very important to both parties. Servier’s turnover in the UK was around £70 million per annum while Apotex made £4 million worth of sales of its generic equivalent before the interim injunction was in place.
The patent was for an invention entitled a “New alpha crystalline form of perindopril tertbutylamine salt, a process for its preparation and pharmaceutical compositions containing it”.
The specification claimed that the invention was an advance from the composition of another of Servier’s patents for the “industrial synthesis of perindopril”, which had an earlier priority date of 17 September 1987 (the ‘341 patent’). The patent in suit claimed that the ‘341 patent did not specify the conditions for obtaining perindopril in a form that exhibited various beneficial characteristics, such as being perfectly reproducible and readily convertible to an industrial scale in a form that allows rapid filtration and drying.
The product covered by the patent was characterised by means of the widely used powder X-ray diffraction profiling (PXRD). PXRD is a technique employed for the purpose of elucidating the different inter-planar distances between parallel planes in which the atoms of alpha crystalline material are located. Essentially, the technique yields a spectrum of graphically presented peaks and troughs which produce a ‘fingerprint’ of the structure of a composition.
Pumfrey J held that Apotex’s material infringed the patent on the basis of: (1) three PXRD analyses carried out on that material; and (2) the fourth experiment conducted, which was a repetition of the example of the patent in suit. Both parties’ expert crystallographers agreed that each of the resulting PXRD patterns indicated a product which fell within the scope of the patent claims.
However, after hearing from the experts, the judge found that in carrying out the teaching in the ‘341 patent, the skilled man would inevitably:
- first carry out the process described on a laboratoryscale (experiment 1 conducted);
- then carry out a pilot-plantscale synthesis (experiment 2 conducted); and finally
- carry out the industrial synthesis of perindopril according to the ‘341 patent.
Servier accepted that the PXRD results of experiment 1 were the same as the patent in suit. Pumfrey J decided that Servier could not demonstrate that, on the balance of probabilities, the alpha form of perindopril was not the inevitable consequence of experiment 1 and therefore the patent in suit was anticipated by the ‘341 patent.
In relation to experiment 2, Servier did not accept that it would inevitably produce the alpha form of perindopril. Pumfrey J restated settled patent law: “For the purpose of anticipation, the prior documents must enable something which inevitably falls within the claim. Where the prior art does not describe the end to be achieved, it is illegitimate to employ a refinement of technique or whatever to cause the desired result to be achieved. Where the sufficiency of a disclosure of a method is under discussion, of course the skilled person is entitled to do such preliminary work and carry out such uninventive refinements, without undue effort, with a view to producing a product falling within the claim.” The judge concluded that Servier were not able to demonstrate that the results of experiment 2 were anything other than the alpha form of the drug. While it was true that the PXRD results of experiment 2 differed from those of the patent in suit, it was not convincingly demonstrated that the differences represented a different crystalline form. The judge also considered that some of the experts’ views tended to suggest that the patent was not clearly drafted in the first place.
Even if the results of experiment 2 did not fall within the patent’s claims, the 341 patent rendered the pilot-plant process obvious to carry out.
Servier sought to amend the patent by replacing the requirement for gradual cooling with a specific temperature range and cooling rate. Pumfrey J found this amendment to be arbitrary and lacking in any inventive step.
The patent was therefore revoked in its entirety.
It was no surprise that just as the patent protecting the drug’s industrial preparation was due to expire (September 2008), the generics companies sought to introduce an alternative drug with the same properties. Keen to maintain its monopoly, Servier sought to enforce a later patent which was found to be invalid in light of the earlier one.
Although the injunction granted by Mann J in August 2006 was continued by consent until trial, there would undoubtedly have been a cross-undertaking in damages. The financial consequences of that undertaking will no doubt be painful for Servier to bear.
Earlier in the year in related proceedings concerning the same patent, Servier settled against two other generics manufacturers, the Polish company KrKa and the Indian company Lupin. Again, the settlement agreements no doubt contained provisions for the event that the patent was later found to be invalid. No doubt letters have already passed between advisers as a result of this latest decision.
The judge was at pains to point out that he did not have the opportunity to see Apotex’s expert witness cross-examined, although he was called for cross-examination. The judge seemed to want to see whether the expert would also be unshaken in his conclusions (as Servier’s counsel had asserted about one of their experts). The judge also seemed disappointed that he did not have the opportunity to compare why the experts had rejected one another’s findings. Apotex’s expert’s evidence therefore stood unchallenged. Since the onus lay on Apotex to show invalidity, the judge said he should be very cautious before not taking that unchallenged evidence at face value.
It is noted that Servier has permission to appeal to the Court of Appeal.