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In a recent decision by the Federal Court of Australia, Justice Gyles found that certain claims of Sanofi-Aventis’ (Sanofi) Australian Patent AU 597784 (AU 784) relating to the dextro-rotatory isomer of methyl alpha-5 (4,5,6,7 - tetrahydro (3,2-c) thioeno pyridyl) (2-chlorophenyl)-acetate (clopidogrel) were invalid for lack of novelty and lack of inventive step. Despite this finding however, claims relating to specific salts of the isomer were found to be novel and not obvious and consequently, were found valid.
Background
Prior to filing AU 784 in Australia in 1988, Sanofi had filed a French patent application for racemic methyl alpha-5 (4,5,6,7 - tetrahydro (3,2-c) thioeno pyridyl) (2-chlorophenyl)-acetate, a chiral molecule (the French Patent).
Chiral molecules comprise two distinct forms of non-super imposable mirror images, known as enantiomers. Synthesis of chiral compounds ordinarily results in a mixture of equal amounts of the two enantiomers, called a “racemic mixture” or a “racemate”. One enantiomer, the levo or (-) enantiomer, rotates plane polarised light to the left, and the other, the dextro or (+) enantiomer, rotates plane polarised light to the right. This property can, however, only be identified when the enantiomer is separated from the racemic mixture. Enantiomers commonly have different biological activities because of their different interactions with other enantiomeric molecules in the body.
In Australia, Sanofi markets Plavix, a platelet aggregation inhibiting agent used to reduce thrombotic events such as heart attacks and strokes. The active ingredient in Plavix is clopidogrel bisulfate (hydrogen sulfate), which is a salt of the enantiomer covered by the claims of AU 784.
The patents
AU 784 claimed the dextro (+) enantiomer, a process for its preparation, the pharmaceutical composition containing it and specified salts (hydrochloride, hydrogen sulphate, hydrobromide and taurochlorate) thereof. Reportedly, the (+) enantiomer had more activity and lower toxicity than the levo (-) enantiomer. The French Patent specifically described each enantiomer of the racemic mixture as well as the racemic mixture itself. Significantly, AU 784 also claimed pharmaceutically acceptable salts of the (+) enantiomer.
The proceedings
Apotex (formerly GenRx Pty Ltd) commenced proceedings against Sanofi in 2007 seeking revocation of AU 784 on several grounds, including that the claims of AU 784 were not novel and were obvious in light of the French Patent. Apotex also claimed that the patent was invalid on the grounds of false suggestion or misrepresentation, inutility, and that the claimed invention was not a manner of manufacture.
Lack of novelty
Sanofi argued that AU 784 was not invalid for want of novelty because the French Patent prior art relied on by Apotex was not an enabling disclosure of the (+) enantiomer. Justice Gyles accepted that, in relation to process claims, an alleged anticipation must contain “clear instructions to do or make something” that would infringe the patentee’s claim if carried out after the grant of the patentee’s patent. However, in relation to a product claim, there must only be a “clear description of something” that would infringe the patentee’s claim if carried out after the grant of the patentee’s claim.
Here, it was found that the earlier French Patent gave Sanofi a monopoly in relation to the making and using of the disclosed racemate and each of its enantiomers, either together or separately. Similarly, Justice Gyles found that the existence and the advantages of each of the enantiomers, as well as those of the racemic mixture, were clearly disclosed in the French Patent. Importantly, Justice Gyles stated that “no doubt, if only the racemate were claimed, there would be a large risk that this would not protect against competition from a drug with one of the enantiomers as the active ingredient”.
Justice Gyles distinguished this case from the situation in Alphapharm Pty Ltd v H LunbeckA/S [2008] FCA 559 (a decision which has been appealed to the Full Court) where there was no express reference to, or claim to, the enantiomers of the racemate in the prior art. In that case Justice Lindgren found that a skilled addressee would understand that the (+) enantiomer of citalopram exists when it is contained in the disclosed racemate, however, for an alleged anticipation to be an “enabling disclosure”, it must point unmistakeably to the enantiomer as distinct from the racemate, as a desirable drug to obtain. In Lindgren J’s opinion the prior art patent claiming the racemic mixture of citalopram did not refer to, or disclose, by implication or otherwise, the existence of the two enantiomers.
Here, Justice Gyles found that the French Patent expressly disclosed the existence of the two enantiomers as having the claimed advantage. Consequently, the French Patent was found to anticipate AU 784 , unless AU 784 could be viewed as a selection patent.
Justice Gyles indicated that selection patent principles set out in Re IG Farbenindustrie AG’s Patent (1930) 47 RPC 289 apply to a patent where a compound claimed is specifically identified in an earlier specification as a member of a larger class, not merely where there is express identification for the first time, of a particular member of a larger class with the special characteristic. Justice Gyles stated that a patent application will overcome a prior publication as a selection patent if:
- there is some substantial advantage to be secured by use of the selected members of a class,
- the whole of the selected members possess the advantage,
- the selection is in respect of a quality of a special character, which can fairly be said to be peculiar to the group, and
- the advantage possessed by the selected members is clearly disclosed in the specification.
Here, it was found that there was substantial advantage to be secured by the use of the (+) enantiomer when compared to the use of either the racemic mixture or the (-) enantiomer and the whole of the (+) enantiomer class of compounds possessed the advantage. Similarly, the advantage was clearly disclosed. However, His Honour did not accept that the advantage gained was the inventor’s own discovery, but was rather a verification of previous predictions in the French Patent that the enantiomers would not have equal qualities. Consequently, claims of AU 784 relating to the (+) enantiomer per se were not capable of being a valid selection from the compounds described in the French Patent.
Despite finding the (+) enantiomer was anticipated by the French Patent, Justice Gyles found that, significantly, the salts of the (+) enantiomer claimed in AU 784 were not clearly described in the French Patent. Consequently, claims 2, 3, 4 and 5 relating to the salts of the (+) enantiomer were not found to have been anticipated.
Lack of inventive step
Justice Gyles acknowledged that an inventive step does not have to be a “flash of genius” but that there must be a step from one thing to another. In deciding whether AU 784 disclosed an inventive step, His Honour applied the test of whether a hypothetical addressee, when faced with the same problem, would have taken as a matter of routine, whatever steps led from the prior art to the invention.
Although generally the starting point for analysis of inventive step is what was in the common general knowledge at the relevant time, because the enantiomer had been previously disclosed in the prior art, the Court looked at the inventive step described in the specification of the patent in suit.
Sanofi argued that the claimed invention was ascertaining that only the (+) enantiomer exhibited platelet aggregation inhibiting activity and that the (-) enantiomer was inactive and less tolerated and that this was not obvious. However, Gyles J held that it was common general knowledge in Australia at the priority date that one of the two enantiomers might contain all of the activity and “the discovery of that characteristic in this case was not so unexpected as to amount to an inventive step”.
Justice Gyles next turned to assessing the inventiveness of the salts of the claimed enantiomer. His Honour said that if the starting point for assessing inventiveness is the single (+) enantiomer, then the salt of the enantiomer would be obvious. However, the inventive step claimed in relation to the salts was not the method of obtaining the salts, but rather the identification of the properties of the salts obtained. Consequently, the claims to specific salts were found to involve an inventive step when compared with the common general knowledge in Australia at the relevant time (which did not include clopidogrel). Unlike the enantiomer claims, the salts were novel compounds without any consideration as selection patents and therefore inventiveness was to be viewed from the starting point of what was common general knowledge.
As a result, while claims of the patent relating to the (+) enantiomer were found to lack novelty and inventive step, claims to specified salts of the (+) enantiomer, including the active ingredient in Sanofi’s product Plavix, the hydrogen sulphate salt, were found to be valid. The Court also rejected Apotex’s arguments that these claims were invalid on the grounds of false suggestion or misrepresentation, inutility, and that the claimed invention was not a manner of manufacture.
Claims to the process of resolving the enantiomers from the racemic mixture were found to be invalid on the ground of obviousness, as the process claimed was routine.
Comment
This case raises the difficult issue of when an Australian patent can be treated as a selection patent. If it is to be treated as a selection patent, does a different obviousness test apply? The question identified by Justice Gyles at para [80], of whether a valid selection patent can exist if the compound claimed was specifically identified in the first patent as a member of a larger class, remains to be definitively resolved.