FACTS OF THE CASE



French Patent Application No 253047 was filed in 1982 by Sanofi Aventis (Sanofi) and disclosed new thieno (3,2-c) pyridine compounds having inhibiting action on blood-platelet aggregation and anti-thrombotic activity. The compounds contained a chiral centre (asymmetric carbon) and thus afford 2 possible enantiomeric forms, or isomers, which may be designated as the (+)- and (-)-enantiomers, depending on the direction in which they rotate plane polarised light. The application, later granted as a patent (the French patent), described the compounds having an asymmetrical carbon and referred to ""each enantiomer and their mixture"". Example 1 illustrated the specific compound methyl -5-(4,5,6,7-tetrahydro (3,2-c) thieno pyridyl) (2-chlorophenyl)-acetate (PCR 4099), which was synthesised as a racemate (a mixture of equal parts of each enantiomer resulting in no net rotation of plane polarised light). Subsequent testing of PCR 4099 indicated adverse side effects and attempts to separate and test the individual enantiomers were undertaken. It was found that the (-)-, or levorotatory-, enantiomer was inactive and that the (+)-, or dextrorotatory-, enantiomer was at least as active as the racemate. Furthermore, toxicology testing indicated that the inactive (-)-enantiomer was more than twice as toxic as the (+)-enantiomer.

The (+)-enantiomer, known as Clopidogrel, was launched in Australia in 1998 as its bisulphate salt under the name Plavix.. It is the subject of Australian Patent No 597784 (the patent), in the name of Sanofi, which was filed in 1988 under the provisions of the Australian Patents Act 1952, (the 1952 Act). The 20 year term expired on 4 February 2008. Under the provisions of Chapter 6 Part 3 of the Australian Patents Act 1990, the term was extended by 5 years, to 2013.

Apotex Pty Ltd (Apotex) sought revocation of the patent under the provisions of the 1952 Act asserting, inter alia, lack of novelty, and inventive step.

THE DECISION

Novelty

Justice Gyles considered the French patent and the corresponding Canadian, Australian and US patents, each of which made express reference to the two enantiomers or their mixture. Despite the absence of any suggestion that either enantiomer had in fact been obtained or tested, or even a description of a method of resolving the enantiomers, His Honour concluded that the individual enantiomers were within the compounds disclosed.

Sanofi contended however, that mere disclosure was insufficient for anticipation, and that the disclosure required by the earlier published patents must be enabling. His Honour reviewed the authorities, and whilst acknowledging that this is reasonable for the anticipation of a process or method claim, it has little relevance to anticipation of a product claim or a claim for a chemical compound by formula. His Honour took the view that in order to deprive the claim of the necessary novelty a publication need only contain a clear description of, or clear instruction to do or make something that would infringe the patentee's claim.

In the case of the French patent, the inhibiting action on platelet aggregation and anti-thrombotic activity was asserted for all compounds of the class claimed, i.e. the racemates and each enantiomer thereof. Acknowledging that this may well have been covetous claiming, particularly in the light of the later finding that the (-)-enantiomer of PCR 4099 was in fact inactive, His Honour was of the view that the claims were nevertheless intended to assert a monopoly over not just the racemate but each individual enantiomer. Accordingly, claim 1 of the patent, directed to the (+)-enantiomer per se and its pharmaceutically acceptable salts in general, was held to be anticipated by the French patent (and corresponding Australian, Canadian and US patents).

This finding was distinguished from the recent judgment of Justice Lindgren in Alphapharm Pty Ltd v Lundbeck A/S [2008] FCA 559 (Alphapharm), reported in our IP Update of September 2008, who found for the novelty of a (+)-enantiomer in view of the prior disclosure of a racemate. In that case, the prior art contained no implied or express reference or claim to the existence of the individual enantiomers separate to their existence in a racemate.

His Honour acknowledged where there might be an exception to his finding of anticipation on the basis of mere disclosure: that being where the patent was for a selection. Notwithstanding that PCR 4099 and its enantiomers were expressly disclosed in the prior art, His Honour did acknowledge that a selection may nevertheless be from a small class, in this case the (+)- and (-)-enantiomers of PCR 4099. His Honour then proceeded to determine whether the (+)-enantiomer satisfied the well-established requirements for selection:

* there must be some substantial advantage secured by the selected members;

* the whole of the selection must possess the advantage;

* the selection must be in respect of a special character peculiar to the group; and

* the advantage must be clearly disclosed in the specification.

The first, second and fourth criteria were readily found to be satisfied. However, His Honour concluded that the selection was not in respect of a special character peculiar to the selection, noting that the advantages of the (+)-enantiomer were not different in kind from those described for the compounds disclosed and claimed in the French patent, that is to say, low toxicity, excellent tolerance and inhibition properties on blood-platelet aggregation and anti-thrombotic activity.

Notwithstanding the finding against claim 1, claim 3, directed specifically to the hydrogen sulphate salt of the (+)-enantiomer and claim 6, directed to a process for the preparation of the (+)- enantiomer, required separate consideration.

His Honour concluded that although the prior patents referred to addition salts with pharmaceutically acceptable mineral or organic acids, there was no clear or specific disclosure of the hydrogen sulphate salt, and the attack on the novelty of claim 3 failed.

Similarly, as noted above, the prior patents afforded no description of how the (+)-enantiomer could be prepared. Accordingly, claim 6 was also held to be novel.

Inventive Step

The provisions under the 1952 Act regarding inventive step limited consideration to what was known or used in Australia on or before the priority date, i.e. the common general knowledge.

Apotex did not attempt to assert that clopidogrel was part of the common general knowledge, or that the skilled person would have arrived at the (+)-enantiomer on the basis of his or her common general knowledge prior to the priority date of the patent. Instead Apotex relied on the description of inventive step in the specification, being the step from racemic PCR 4099, described in the French patent, to the (+)-enantiomer. Taking the starting point for the step as the racemic PCR 4099, His Honour considered that the inventive step was ascertaining that only the (+)-enantiomer exhibited platelet aggregation inhibiting activity, the (-)-enantiomer being inactive and less well tolerated. However, His Honour accepted that it was common general knowledge at the priority date that one of the two enantiomers might contain all the activity and concluded that the discovery that the (+)-enantiomer was responsible for the activity was not so unexpected as to amount to an inventive step.

Claims 2-5 of the patent were directed to specific salts of the (+)-enantiomer: hydrogen sulphate, taurocholate, hydrobromide and hydrogen chloride. His Honour noted that the conversion of the (+)-enantiomer to the specific salts was not suggested to have any difficulties, being described as achieved in a standard manner by standard methods and it was observed that if the (+)-enantiomer was common general knowledge, each of the salts would be obvious. However, the inventive step rested not on the method for obtaining the salts but on the properties of the salts themselves, which were held to be novel, without any special consideration to selection patents. Accordingly, the attack of lack of inventive step on the claims to the specific salts failed.

His Honour also held that the method claims, directed to a process for obtaining the (+)-enantiomer, were merely classic processes being applied to a known compound, and accordingly found them obvious.

Apotex also alleged that the patent was obtained on a false suggestion or representation, particularly with regard to the term ""unexpected"" as used in relation to the finding that the (+)-enantiomer alone was responsible for the activity. His Honour refused to find so, noting that in any event, even if they were false, there was no indication that these statements materially led to grant of the patent. Indeed, His Honour dismissed the term as likely to be a patent attorney's ""puff"" rather than a serious statement of fact!

Apotex has appealed the decision.

COMMENTARY

It is clear that whilst individual enantiomers are not inherently unpatentable in light of a prior disclosure of the racemate, each case must be judged on the relevant facts. Here, prior disclosure of a specific racemic compound, and general reference to the enantiomers was considered sufficient to anticipate a subsequent claim to the (+)-enantiomer of that compound, notwithstanding the absence of any specific teaching or suggestion as to resolution of the racemate or any indication as to which enantiomer possessed the desired biological activity.

Whilst the French patent did not explicitly disclose any method for preparing the individual enantiomers, evidence presented by the expert witnesses clearly established that a range of techniques for obtaining enantiomers from a racemate was well known in the art prior to the earliest priority date, including diasteriomeric salt formation as claimed in claim 6 of the patent. On that basis, it could be argued that, notwithstanding the absence of explicit teachings, the disclosure of the French patent was nevertheless enabled by virtue of the skilled addressee's common general knowledge, in light of which any specification must be construed. Taken to an extreme, however, the Court's conclusion that mere prior disclosure of a chemical compound is sufficient for anticipation may conceivably lead to a situation where a ""fantasy"" disclosure may deprive new (in the sense of newly discovered or prepared for the first time) compounds from subsequent patent protection.