Extension of term denied... A blow to evergreening?

Date:	06 August 2009
Author:	Paul Whenman

H Lundbeck A/S v Alphapharm Pty Ltd [2009] FCAFC 70

Key Points:

Existence per se of a racemic mixture in the prior art is not novelty destroying for either of the enantiomers.
Existence per se of a racemic mixture in the prior art may not deprive the enantiomers of an inventive step.
The date for which an extension of term application must be filed in relation to an enantiomer is 6 months from when the racemic mixture, which included the enantiomer, is included on the Australian Register of Therapeutic Goods (ARTG).

This case relates to the Lundbeck Australian patent no 623144 which contains claims to the pharmaceutical substance escitalopram and processes for producing it. Escitalopram is the S-enantiomer or (+)-enantiomer of the compound citalopram which is used for treating depression. Citalopram is the subject of Australian patent no 509445 and is a racemic mixture of the two enantiomers escitalopram and (-)-citalopram in equal proportion.

Australian patent no 623144 (the Escitalopram patent) was filed 13 June 1989 with a claim to priority of 14 June 1988.

In the initial proceedings, a single judge of the Federal Court was required to make a number of determinations, including:

(1) Are the claims to the compound escitalopram in the Escitalopram patent valid?

(2) Had an extension of term for the Escitalopram patent been validly granted by the Commissioner of Patents?

In a decision issued in April 2008, a single judge of the Federal Court found that:

(a) The claims to the compound were novel and non-obvious; and

(b) That because Lundbeck had filed its application for an extension of term outside the time limit, the Commissioner of Patents had no power to extend the term of the Escitalopram patent. The time frame for filing an application for an extension of term is 6 months from a when pharmaceutical substance is included on the Australian Register of Therapeutic Goods.

Subsequently, this decision was appealed to the Full Federal Court. In a decision dated 11 June 2009, (http://www.austlii.edu.au/au/cases/cth/FCAFC/2009/70.html) the Appeal Court has agreed with the initial decision on both the points set out above. Whilst this decision may be appealed to the High Court, this decision on extension of term has far-reaching consequences for the pharmaceutical industry. In particular, it is likely that many drugs that are enantiomers, will have been included on the ARTG as a component of a racemic mixture but an extension of term application will have only been filed when the enantiomer per se was included on the ARTG. Based on the present decision, any extension of term granted in these circumstances may be invalid, depending on the timing of the ARTG inclusion.

The decision on novelty and obviousness is of somewhat lesser importance in the sense that the conclusion reached by the Court is fact based and follows the approach laid down by the High Court.

A more detailed discussion on each of the issues is set out below.

Novelty

Although Courts are routinely required to determine if patents are valid and infringed, this case is unusual in a number of respects. Specifically, in assessing novelty, the Court was required to consider whether or not disclosure of the racemic mixture in the citalopram patent 509445 was novelty destroying for one of enantiomers in the racemic mixture, namely escitalopram.

In making a finding of novelty, the Court concluded that the citalopram patent 509445 was not an anticipation in relation to escitalopram.

At paras 193/194, Bennet J states that:

"The prior citalopram patent described the racemate. It did not describe the pure or isolated (+)-enantiomer. There is no anticipation unless the disclosure of the racemate was, to the skilled addressee, a disclosure of the (+)-enantiomer. ...the skilled but non-inventive addressee would have understood that (+/-)-citalopram consisted of the (+)-enantiomer and the (-)-enantiomer and would have been able to identify the formulae for the S and R enantiomers but would not have known in the absence of experimentation which was the (+)-enantiomer and which the (-)-enantiomer. ...these facts would not point specifically to the independent existence of the enantiomers. They did not disclose an invention which, if performed, would necessarily infringe the Patent.

It is the case that the skilled addressee knew that the racemate could be resolved into the enantiomers but there was nothing to tell him or her to do so. Further, the prior citalopram patent was silent as to the means of obtaining the enantiomers and there were different methods available to try to do so. There were no clear and unmistakable directions to obtain the enantiomers. Some of the available methodology may have been successful, other methods may not."

Obviousness

In considering a second prior art document "The Smith Article", the Court concluded that although this document disclosed the structural formula for both enantiomers, in fact it taught away from escitalopram because the author incorrectly concluded that the (-)-enantiomer ought to be the most potent. In the Court's estimation, the article was a distraction and the person skilled in the art would have been required to conduct further experiments and research to achieve the invention. It was concluded that at the priority date, obtaining the individual enantiomers would not have been adopted as a matter of routine. Further, since citalopram was already known to be very selective in its activity, there was no significant motivation to obtain the enantiomers of citalopram.

Extension of Term

The Court's finding in relation to the extension of term is a logical outcome of its construction of the claim to escitalopram and arises out of the language of the Patents Act. Section 71(2) of the Patents Act relevantly requires an application for an extension to be made within six months after the date of the "first inclusion" in the ARTG of "goods that contain, or consist of, any of the pharmaceutical substances referred to in subsection 70(3)".

It was established that Lundbeck gained inclusion of the product CIPRAMIL, (containing citalopram) on the ARTG on 9 December 1997. It was also established that Lundbeck gained inclusion of the product LEXAPRO, (containing escitalopram) on the ARTG on 16 September 2003.

The Court held that having regard to the language of section 71(2), escitalopram was contained in CIPRAMIL. Accordingly, an extension of term for escitalopram could only be validly based on an application filed within 6 months of the inclusion of CIPRAMIL on the ARTG. Since the extension application for the escitalopram patent was filed outside of the statutory 6 months period, the extension of term granted was found to be invalid.