Today, the majority of the world’s top selling pharmaceutical products have a chiral molecule as their active pharmaceutical ingredient. Increasingly, this chiral molecule is a single enantiomeric form of that molecule. As the importance of enantiomeric compounds to the pharmaceutical industry has increased, so has the number of patents that relate to such compounds. This, in turn, has led to an increasing amount of litigation with respect to such patents as the patent holders assert those patents to protect their valuable intellectual property and the revenue stream that it generates and generic manufacturers challenge those patents in order to gain access to a piece of that revenue stream.
This article will discuss the first Australian court decision concerning the infringement and validity of an enantiomer patent, Ranbaxy Australia Pty Ltd v Warner-Lambert Company LLC (No 2)  FCA 1787.
Chiral molecules and enantiomers
Chiral molecules are molecules that exist in distinct mirror image forms that cannot be superimposed on each other. These mirror image forms are called enantiomers.1
Purified enantiomers exhibit identical physical and chemical properties to their mirror image, however, they often exhibit very different biological activity. For instance, one enantiomer can have most, if not all, the biological activity. Further, toxicity may be associated with only one enantiomer. This was most unfortunately illustrated with the drug thalidomide, whose inactive enantiomer was ultimately responsible for severe birth defects in children whose mothers took the drug during pregnancy.
Ranbaxy Australia Pty Ltd v Warner-Lambert Company LLC (No 2)
The Ranbaxy case concerned the infringement and validity of a patent claiming, inter alia, the R- enantiomer of the pharmaceutical compound atorvastatin calcium (the "Enantiomer Patent"). The compound claimed in the Enantiomer Patent is marketed in Australia as "Lipitor" by Warner-Lambert. Atorvastatin calcium is claimed in an earlier Warner-Lambert patent (the "Racemate Patent") and is used in patients to reduce cholesterol by inhibiting its synthesis.
Ranbaxy challenged the validity of the Enantiomer Patent on the following bases:
- that the enantiomeric compound is not a patentable invention as it is not a manner of manufacture ("patentable invention argument")
- that the patent was obtained on a false suggestion or misrepresentation; and
- that the invention claimed was not useful.
Not a patentable invention
In support of its patentable invention argument, Ranbaxy provided evidence of a strong line of data (both by way of published journal articles and patent specifications) demonstrating that a skilled addressee reading the Racemic Patent would have known that the compound claimed was a racemic compound and therefore comprised an S- and R- enantiomer, and that the activity was likely to reside in the R-enantiomer.
Relying on this evidence, Ranbaxy argued that the R-enantiomer was already disclosed in the Racemate Patent and that this pharmaceutical compound had a known use; that is, it was known to be suitable for inhibiting the synthesis of cholesterol. On this basis, Ranbaxy argued that merely claiming the R-enantiomer of a known compound and applying the compound to a use for which it was already known to be suitable meant that the patent lacked the necessary quality of inventiveness to be a patentable invention.
The Court did not agree, and in fact noted, that this was a de facto attack based on novelty and inventive step, grounds of invalidity that Ranbaxy had chosen not to pursue. Although the Court held that the skilled addressee would have been able to recognise the compound claimed in the Racemic Patent as consisting of an S- and R- enantiomer, and that it was likely that one enantiomer was more active than the other, the Court further held that a number of important choices and selections would have had to have been made by a skilled addressee of the Racemate Patent to move to the point of identifying, and then claiming, the compounds in the Enantiomer Patent. The Court thus held that Ranbaxy had failed to establish that the Enantiomer Patent claimed nothing but a new use of an old substance.
To this extent, the decision in the Ranbaxy case is consistent with the recent UK decision Generics (UK) & Ors v H Lundbeck A/S  EWHC 1040. In that case, it was held that the inventive step taken by the inventors of the patent claiming a single enantiomer was not deciding to separate the enantiomers, but finding a way it could be done.
False suggestion and lack of utility
Despite surviving this challenge, the Enantiomer Patent was revoked on the basis of false suggestion and lack of utility. Justice Young held the Enantiomer Patent specification to represent that the R-enantiomer had ten times greater activity than the racemate. The evidence presented at trial demonstrated that this promise was not capable of being achieved and that, in fact, the R-enantiomer had only two times greater activity than the racemate. The Court thus held that the Enantiomer Patent was granted on the basis of a false suggestion. The Court also held that the invention was not useful, as the test for utility is directed at the results promised in the specification, and the R-enantiomer failed to achieve the promised results.
Another enantiomer patent decision pending
It should be noted that the Federal Court has recently heard another matter concerning the revocation of a patent claiming a single enantiomer (Alphapharm v Lundbeck). This concerns the same enantiomer as was the subject of challenge in Generics (UK). It is unlikely, however, that this decision will be handed down before early 2008.
1 A chiral molecule may have one or more chiral centres. Each chiral centre will have an enantiomeric pair. Each chiral pair is composed of an S-, for sinister (Latin for left), enantiomer and an R-, for rectus (Latin for right), enantiomer.
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