Alert

Who does this affect?

Patentees and those wishing to challenge the validity of patents on the ground of obviousness, particularly in the context of a claim to an enantiomer or specific salts where the racemic mixture is disclosed in prior art.

What do you need to do?

Be aware of the complexities of the issues and the various approaches taken by the Courts in determining the validity of these patents.

Authors
John Cusick  
Senior Associate

Suzy Groom  
Solicitor

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Kim O'Connell  
Partner
T +61 2 9296 2188

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Melbourne
Robert Cooper  
Wayne McMaster  

Brisbane
John Swinson  

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The Full Federal Court has handed down its findings in Apotex Pty Ltd v Sanofi-Aventis [2009] FCAFC 134, an important decision in relation to the validity of patents claiming enantiomers of known racemic compounds, and their salts.

The Full Court upheld Justice Gyles’ decision at first instance that claims to the dextro-rotatory enantiomer, or d-enantiomer of a compound were invalid for lack of novelty and lack of inventive step. It also upheld Justice Gyles’ finding that particular salts of the d- enantiomer were novel, however overturned His Honour’s findings that the particular salts of the d-enantiomer were inventive.

Our previous alert on Justice Gyles’ decision at first instance can be found here.

Background to the proceedings

Sanofi was the patentee of earlier French (2530247), Canadian (1194875) and Australian (554358) patents, the prior art, which claimed the racemic mixture of methyl alpha-5 (4,5,6,7 - tetrahydro (3,2-c) thioeno pyridyl) (2-chlorophenyl)-acetate, as well as pharmaceutically acceptable salts of that compound. A racemic mixture contains two enantiomers, the d enantiomer and the levorotatory, or l- enantiomer, distinguishable only in the way they rotate plane polarised light. Subsequent clinical trials of each enantiomer found that the d- enantiomer was more efficacious and better tolerated in patients than either the levorotatory, or l- enantiomer, or the racemic mixture.

Sanofi is the owner of the patent in suit, AU 597784, which claims the isolated d- enantiomer from the racemic mixture of the molecule and its pharmaceutically acceptable salts, as well as, specifically, the hydrochloride, hydrogen sulphate, hydrobromide and taurocholate salts of the d- enantiomer. The d- enantiomer is known as clopidogrel, and clopidogrel bisulphate is marketed by Sanofi as Plavix, a platelet aggregation inhibiting agent used in the prevention of heart attacks and strokes.

Apotex originally commenced proceedings in the Federal Court claiming that the patent in suit was invalid and that all of the 11 claims should be revoked. Sanofi cross-claimed for orders restraining Apotex from infringing the patent. At first instance, Justice Gyles found the claim for the d- enantiomer was anticipated by the prior art, as well as being obvious in light of the common general knowledge. However, claims to the hydrochloride, hydrogen sulphate, hydrobromide and taurocholate salts of the isolated enantiomer were novel and were not obvious.

Sanofi appealed Justice Gyles’ findings in relation to lack of novelty and lack of inventive step and Apotex appealed Justice Gyles’ finding that the claims of the patent which claimed particular salts of the d- enantiomer were valid, submitting that these claims lacked both novelty and inventive step.

Novelty

In their joint judgment, Justices Bennett and Middleton, with whom Justice Emmett agreed, found that the prior art patents disclosed and claimed the racemic mixture as well as both enantiomers of the compound.

In finding that the claim to the d- enantiomer was not novel, Justices Bennett and Middleton referred to their previous judgment in H Lundbeck A/S v Alphapharm Pty Ltd (2009) 81 IPR 228 as authority for the proposition that an invention will be anticipated where a prior publication discloses exactly what is claimed, in circumstances where the skilled addressee is able to add any missing information “as a matter of course” and without exercising any inventive ingenuity or undue experimentation. When deciding whether an invention is novel, the Full Court indicated that the question must always be whether the alleged anticipation is sufficient to enable the skilled addressee to perceive, understand, and, where appropriate, apply the prior disclosure within the ordinary limits of trial and error to obtain the invention.

Sanofi submitted that there was no clear disclosure of the d- enantiomer in the prior art patents because they did not disclose a method of producing or resolving the d-enantiomer, or that the d- enantiomer had in fact been isolated. However, the Court found that it is not necessary for a prior publication to set out a method of preparing what it is that is claimed. The Court found that there was in fact a clear disclosure of each of the enantiomers in the prior art and the skilled reader would be able to separate the enantiomers and understand the methods required to do so, which were routine. Similarly, because those enantiomers were also claimed in the prior art, there was a clear direction to the skilled addressee to prepare each enantiomer.

Salts of the d- enantiomer

While the Court found that the d- enantiomer was anticipated, the Court upheld Justice Gyles’ decision that claims to the salts of the d- enantiomer were novel because the prior art only referred to the salts of the racemate, not the salts of the individual enantiomers. Similarly, the Full Court noted that all of the pharmacological and toxicological testing disclosed in the prior art was carried out on the salts of the racemate rather than the salts of the individual enantiomers. There was nothing in the prior art which provided a clear description of the salts claimed in the patent in suit, or clear instruction or direction to make the particular salts claimed.

Inventive step

At first instance, Justice Gyles found that it was common general knowledge at the priority date of the patent in suit that one enantiomer of a racemic mixture may be responsible for all of the biological activity of the racemate. Consequently, the alleged discovery of the inactivity of the l- enantiomer, the asserted inventive step in relation to the isolated d- enantiomer, was not so unexpected as to properly amount to an inventive step. The Full Court agreed.

At first instance, Justice Gyles also found that the starting point for an assessment of obviousness was not the d- enantiomer disclosed in the prior art, but rather, the common general knowledge, and consequently, that the salts of the enantiomers were not obvious. On appeal, Apotex accepted that neither the racemic compound or the prior art were part of the common general knowledge at the priority date, however argued the common generally knowledge was not the appropriate starting point from which to consider inventive step.

The Full Court found that claims to the salts of the d- enantiomer were obvious, irrespective of whether the starting point was the racemic mixture or the isolated d- enantiomer. The Court stated that it is the invention that is described in the specification which must be examined to determine the question of obviousness, and here, the specification makes clear that the selection of the racemate to be resolved did not form part of the invention. Rather, it was clear from the specification that it was the process of separating the enantiomers of the mixture to obtain the  
d- enantiomer, and in turn, the pharmaceutically acceptable salts of that enantiomer that was the subject matter of the claims. The Full Court emphasised that the invention to be assessed for obviousness is ascertained from the patent and the obviousness of the invention as claimed is then assessed by reference to the common general knowledge at the priority date.

In this case, the invention as described in the specification assumed that the skilled addressee was in possession of the racemate and the knowledge it had biological utility, even though that skilled addressee would not know the contents of the prior art, or for that matter, anything else that was not part of the common general knowledge. That is, because in this case the problem was described in the patent as being the difficulty of purifying the d- enantiomer and obtaining suitable salts, the starting point for a consideration of obviousness is the skilled addressee armed with the biologically active racemate and the common general knowledge.

Crucially, the Full Court found that although arriving at the specified salts involved choice and trial and error, those steps were routine and did not involve an inventive step.

Comments

The decision affirms the fact that in order to be novelty defeating, a prior publication must disclose precisely the thing claimed in the later patent.

The Full Court’s decision is also an important clarification of the approach that will be taken by the Courts in assessing inventive step, and in particular, how to identify the starting point for the relevant test. They make it clear that the starting point from which inventive step is to be assessed is to be found by analysing the description of the invention given in the patent. The starting point described can be taken to be the starting point for the hypothetical skilled worker embarking on the same task, armed with the common general knowledge.