Is Smith Kline Beecham’s Patent for Rosiglitazone Maleate (Avendia) Invalidated by an Earlier Patent Claiming Rosiglitazone and its Salts?

Rosiglitazone Maleate is a patented drug that is manufactured by Smith Kline Beecham (SKB) under the trade name Avendia and is used for the treatment of type II Diabetes.

When Israel drug manufacturers Unipharm and Trima started manufacturing generic versions, SKB filed for an injunction and also for damages. Unipharm and Trima’s defense was that the patent in question, IL 106904, which claims priority from an earlier British application UK 9218830/9 is invalid, since it lacks novelty and inventive step in light of an earlier European patent EP 0306228 that published before the priority date.

The Court of First Instance found that the generic product, Rosi, produced by Unipharm and Trima infringed the IL 106904 patent, which was upheld over the prior patent. Lack of sales rendered the issue of unfair trade and compensation of the patentee for lack of sales moot. The decision was appealed to the Israel Supreme Court.

In the Appeal, Unipharm and Trima claimed that the Court of First Instance was wrong to determine that since there was novelty and inventive step, the issue of whether the patent in question was a selection patent did not need addressing. They argued that although a preferred salt had been isolated, it could not fairly be used to extend the term of protection beyond the expiry date of the earlier patent. They also argued lack of enablement. Finally, they pointed out that although advantages were claimed, this was in a qualitative and not a quantitive manner.

The court reminded the parties that it does not review factual determinations of the Court of First Instance, but only reviews matters of law. It went on to rule that even were the wide claim 1 to be invalidated, nevertheless Claim 4 for the specific Rosiglitazone Maleate could survive on its own merits if shown to be novel and inventive as it was widely supported by the specification. They also defended the principle of At Risk manufacture, pointing out that the Law (Section 182) allows invalidity as a defense for patent infringement.

The Court of First Instance was impressed by the patentee’s witnesses and by the fact that the defendants witness admitted that Rosiglitazone Maleate was novel. The fact that the patentee could show trial and error in the research program, that they considered other salts like the hydrochloride more likely to be appropriate and almost gave up the project for lack of progress as indicative that the selected sale is not obvious. The Court of Appeal saw no reason to overturn this ruling. Pointing out that the Israel Patent Law for Novelty requires enabling disclosure, the court pointed out that nowhere is Rosiglitazone Maleate mentioned in the earlier patent, and so was novel there over. By virtue of the earlier patent teaching basic salts and the present invention being an acidic salt, in view of improved efficacy, higher solubility and stability, the Rosiglitazone Maleate was considered novel and inventive. As to enablement, the court pointed out that the ease of copying of the patented salt by the man of the art, on the basis of the disclosure in the patent is evidence that the description is enabling.

Costs of NIS 60,000 were awarded to the patentee.

The Case: Appeal 8802/06 Unipharm et al. vs. Smith Kline Beecham et al. given on 18 May 2011 by Retired Judge Fructzia an endorsed by Judge Heyot and Judge Fogelman.

Comments

This decision is notable as it is rare that Adi Levit, representing Unipharm, loses to the innovative drug industry represented by Richard Luthie.

There are a number of points of interest. Appellants claimed that the Rosiglitazone Maleate was claimed in a dependent claim (claim 4) and if the main claim falls, this dependent claim falls with it. Such an argument is found in a couple of decisions of the outgoing Arbitrator of Intellectual Property at the Patent Office, Noach Shalev Shlomovich. In Giraffa vs. Melnicke, Shlomovitch rules that where a main claim is invalid, all dependent claims also fall. I criticized that fiercely and he admitted to me once that this was a mistake. Nevertheless, in other oppositions, where main claims are shown to be invalid, he has punished the applicant for greed and cancelled the dependent claims. In this case, the Supreme Court has ruled that where there is adequate support for the dependent claim and that it is fairly based on the specification, it survives even if the independent claim on which it is based is invalidated. It is hoped that this Supreme Court ruling is considered as binding precedent and this odd issue is laid to rest.

The claims of the prior art do relate to salts of rosiglitazone which does literally include Rosiglitazone Maleate. Since the specification relates to basic salts only the court has effectively construed the term ‘rosiglitazone and its pharmaceutical acceptable salts’ to mean basic salts only. Frankly I am not sure that this is needed. If some specific molecule is indeed surprisingly found to have advantages over the prior art, this could fairly be patentable. When the main patent expires, other salts, not within the scope of the second patent will become public domain.

As is often the case, it is the obiter that is most interesting. In this case, the court has essentially rejected selection patents as a separate class, arguing that previous Supreme Court rulings related to the mandatory regime before the Israel Patent Law was passed and that by not relating to selection patents, the Israel Law has essentially rejected them as a class. Another interesting point made is that secondary uses of known pharmaceuticals are patentable inventions. In the past, the title of an Israel patent has been considered unimportant, and it is generally considered as used for classification purposes only. In this ruling it is clear that the courts do consider the title as indicative of the scope of the invention. Reiterating Section 49 the court has ruled that it considers that the scope of the patent includes its nucleus (pith and marrow?) and the exact wording of the claims is not all-important. It seems that unnecessary limitations in the claim language will not be considered limiting of the scope of the monopoly.

 



Categories: drugs, Israel, Israel Patent, pharmaceuticals, pharmaceuticals and Biotechnology

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