In a much anticipated decision the Full Federal Court has upheld the validity of Lundbeck’s escitalopram patent for its 20 year term but would not allow an extension of the term.

Background

Earlier this month the Full Federal Court published its decision in Lundbeck v Alphapharm1, an appeal from Lindgren J’s decision in the Federal Court in June 2008. The appeal related to the validity and infringement of the patent for escitalopram, an anti-depressant marketed in Australia as Lexapro, as well as the extension of the patent term. To allow the launch of generic products shortly after the expiry of the patent’s usual 20 year term on 13 June 2009, competitors had sought revocation of the patent on a number of invalidity grounds including lack of novelty and challenging the patents extension of term.

The proceedings have been of particular significance to those in the industry that seek to patent chemical compounds that are enantiomers. Enantiomers are isomers that are non-superimposable mirror images of each other, like a person’s left and right hand. A mixture of two enantiomers in equal parts is known as a racemate or a racemic mixture. They can be distinguished from each other by the direction in which they rotate plane-polarised light. Depending on the direction of the light, enantiomers are designated as either (+) or (-). Escitalopram is the (+)-enantiomer of the racemate Citalopram, which was patented earlier and was one of the first antidepressants marketed in its particular class.

Construction of the Patent

Although the principles of claim construction are generally well accepted, the application of those principles can be difficult and may result in differing views about the scope of claims and as a consequence the validity and infringement of a patent.

On appeal, Bennett J (with Middleton J agreeing) stated that the primary issue to be resolved was, does (+)-Citalopram in claim 1 of the patent denote and claim the purified or isolated (+)-enantiomer, or the (+)-enantiomer whether alone or as part of a mixture, or the (+)-enantiomer as present in a racemate? Lindgren J had found that that claim 1 referred to the separated or isolated or pure (+)-enantiomer. Bennett J agreed with that aspect of the construction.

However, at trial Lindgren J also concluded that Claim 1 referred to Escitalopram that is at least 95% pure. Bennett J disagreed with the finding of purity, refusing to qualify the type of purity where none was made clear in the specification. As a demonstration that reasonable minds may differ, Emmett J dissented, and considered that Claim 1 related to the product or substance, the (+)-enantiomer, and there was nothing to suggest that it was to be isolated or of a particular property. This construction led to different conclusions about novelty.

Novelty

At trial Lindgren J had held that an enabling disclosure in the context of a product claim means simply that the earlier disclosure must point unmistakably to the (+)-enantiomer of Citalopram as distinct from the racemate. It was held that there was no enabling disclosure and the product claims were valid. Bennett J considered that the use of the term “enablement” in Australia tended to cause some confusion between anticipation and sufficiency. Where a prior disclosure falls short of complete disclosure he said you must, with evidence from a person skilled in the art as to the terms of art and nature and extent of the disclosure, determine whether the prior disclosure is sufficient to enable the skilled addressee to perceive and understand the claimed invention.

There were 2 prior art documents relevant to the question of novelty. The first was the Citalopram patent. On appeal Bennett J agreed with Lindgren J, and found the Citalopram patent does not point specifically to the independent existence of the enantiomers, and does not disclose an invention which, if performed, would infringe the patent. Although the skilled addressee knew the racemate could be resolved into enantiomers there was nothing telling him or her to do so. The second document was a journal article that predicted one enantiomer would be more potent than the other but as it could not be determined which one without an inventive step there was accordingly no anticipation.

Infringement

The infringement of the method of manufacture claim by the use of the same method differing only by the replacement of a substituent group that had no material change to the way the process worked was appealed. Bennett J (Middleton J agreeing) agreed with Emmett J that claim 6(b) was infringed, and overturned Lindgren J’s primary decision because of the use of a particular chemical symbol in the claim instead of a symbol used elsewhere in the claims when substitution is permitted. The absence of that particular symbol in respect of the substitutable group signified the group was an essential integer of the method and substituting did not infringe the method.

Extension of the patent

Escitalopram is a pharmaceutical substance for the purposes of s70 of the Patents Act 1990 in relation to the extension of patent terms. As a claim for a substance in the formula described it is also a pharmaceutical substance per se and there is no question that it in substance falls within the scope of the claims. The other conditions to satisfy were that goods containing or consisting of Escitalopram must be included in the Australian Register of Therapeutic Goods (ARTG) and the period beginning on the date of the patent and the first regulatory approval date for the substance was at least 5 years.

The patent extension had initially been applied for and the period calculated on the basis that Escitalopram was the first good containing or consisting of that substance included on the ARTG. The question was, however, whether the first regulatory approval date for the substance was the inclusion of Citalopram on the ARTG because it contained Escitalopram in the racemate and the per se expression is only used in relation to the nature of the patent claims and should not be imported into other provisions. At trial Lindgren J considered this to be the case and on appeal Bennett J found his reasoning compelling. Bennett J expressed some reservation about the reliance of the decision of Wilcox J in Merck & Co Inc v Arrow Pharmaceuticals2 that a de minimus inclusion was sufficient.

In addition Bennett J held that the terms ‘containing’ and ‘consisting’ do not involve looking at the therapeutic effect of the pharmaceutical substance. Rather, it is said, it is a simple comparison of the pharmaceutical substance with the ‘ingredients’ of the goods on the ARTG. There is also no requirement to contrast effectiveness nor consider the purity.

Watch this space

Pending Lundbeck’s special leave application to appeal to the High Court, The Full Court has granted Lundbeck a stay of the order for removal of the patent term extension from the Register. It is interesting to note that Lundbeck has also filed a new complete application for a Method of Preparation of Escitalopram on 6 February 2009.