H Lundbeck A/S and anor v Alphapharm Pty Ltd  FCAFC 70
The Full Federal Court handed down its long-awaited decision in Lundbeck A/S and anor v Alphapharm Pty Ltd with mixed results for the patentee.
The case relates to Lundbeck's patent for escitalopram, the (+)-enantiomer of citalopram, a pharmaceutical used in the treatment of depression. A number of issues of particular interest to the pharmaceutical sector were addressed. Specifically, it was found that:
- an enantiomer of a "known" racemate may be patentable;
- inclusion of a racemate on the Australian Register of Therapeutic Goods (ARTG) is considered inclusion of its constituent enantiomers – meaning that in many cases the patent covering the enantiomer may not be eligible for an extension of term; and
- a claim to a dosage form may be invalid if it specifies a range of quantities of active ingredient outside those shown by the evidence to be effective.
Enantiomer patent valid
Chemical compounds having the same atoms can exist in two (and sometimes many) different forms depending on the spatial arrangement of the atoms. When two forms of the compound are non-superimposable mirror images of each other (like a person's left and right hand), they are called enantiomers. A mixture of enantiomers is a racemate. In many cases only one enantiomer of a pharmaceutical compound is active.
Lundbeck's patent covering the racemate citalopram has expired. As indicated above, the present decision relates to Lundbeck's patent covering one of the two enantiomers of citalopram, the (+)-enantiomer, which is the active form.
The Court was required to determine whether claim 1, directed to the (+)-enantiomer, was anticipated by the disclosure of the racemate citalopram (which comprised both enantiomers). Bennett and Emmett JJ took different approaches to the construction of claim 1. Emmett J took a somewhat literal approach and found that nowhere in claim 1 was it specified that the enantiomer was "substantially pure" or "substantially separated from" the (-)-enantiomer. Moreover, he indicated that it would have been possible to include these qualifying words into claim 1. He went on to find that to read into claim 1 such qualifying words is impermissible as a matter of construing the clear and unambiguous words used by Lundbeck. Accordingly, he concluded, claim 1 does not require that the (+)-enantiomer, be separate from the (-)-enantiomer. In view of this construction, he found that the disclosure of citalopram anticipated claim 1 and dependent claims.
Bennett J (with whom Middleton J agreed) took a more purposive approach to the construction of claim 1. She noted that the patent is entitled "(+)-enantiomer of citalopram and process for the preparation thereof" and that it discloses a method for the preparation of the isolated (+)-enantiomer. Accordingly, Bennett J found that the skilled addressee would construe claim 1 as referring to the isolated (+)-enantiomer. However, she did not agree with the primary judge that claim 1 should be construed to limit the purity of the (+)-enantiomer to at least 95% purity.
In relation to determining the novelty of claim 1, Bennett J indicated that there is no anticipation unless the disclosure of the racemate citalopram was, to the skilled addressee, a disclosure of the (+)-enantiomer. In this regard, she indicated that there were no "clear and unmistakable directions" to obtain the enantiomers and, as such, the prior citalopram patent was found not to anticipate the claims of the escitalopram patent.
Extension of term revoked
Lundbeck's escitalopram patent had been extended for five years, until 13 June 2014, under the Australian provisions for extension of patent term.
A number of criteria must be fulfilled in order to render a patent eligible for an extension of term. One requirement is that the claims of the patent must define a pharmaceutical substance per se. Another is that goods containing, or consisting of, the pharmaceutical substance per se must be included on the ARTG. In addition, an application for an extension of term must be made within six months of (a) the date of first inclusion of the relevant product on the ARTG; or (b) the date of grant of the patent – whichever of the two dates is the later.
Lundbeck applied for an extension of term of their patent on 22 December 2003 based on the claims to escitalopram (a pharmaceutical substance per se) and inclusion of its product Lexapro (escitalopram) on the ARTG on 16 September 2003. However, the racemate Cipramil (citalopram) was included on the ARTG on 9 December 1997. As such, the critical issue was whether the registration of Cipramil could be considered the first inclusion of the enantiomer escitalopram on the ARTG for the purposes of the relevant section of the Patents Act (s70(3)).
The Court found that there is no requirement to consider either the effectiveness or the purity of the pharmaceutical substance contained in the goods included on the ARTG. Moreover, there is no suggestion from the words of s 70(3) that the relevant "goods" could, or must, include no more than one pharmaceutical substance. It was found that citalopram contains both (+) and (-) enantiomers in equal proportions and, as such, satisfies s70(3) in relation to the inclusion of escitalopram on the ARTG. Accordingly, it was held that the Cipramil registration date was the date of first inclusion of escitalopram on the ARTG. Consequently, the application for extension of term was made out of time i.e. well beyond the six month deadline after registration of Cipramil, and the patent was not entitled to an extension of term. The expiry date of the patent was therefore constricted to 13 June 2009.
Dosage form invalid for want of utility
At first instance, Lindgren J had held that a claim to a dosage form comprising escitalopram in an amount of 0.1 to 100 mg was invalid for want of utility since the evidence showed that 5 to 40 mg was the minimum to maximum effective range. His Honour accepted that 100 mg was not harmful. The Full Federal Court found that Lundbeck had not established any error on the part of the primary judge and, consequently, his ruling on this point stood.
Ramifications for patentees
In light of this decision, patentees holding rights to Australian patents covering enantiomers may feel secure in the knowledge that their patents are not going to be held invalid based only on disclosure of the racemate. It should be noted, however, that whether an enantiomer patent is ultimately found to be valid will depend on the precise nature of the disclosure of the racemate and whether all other criteria for patentability – including inventive step – are fulfilled.
Further, patentees holding enantiomer patents should note that any patent term extensions already obtained may be vulnerable (see below re appeal). This is likely to lead to generic manufacturers attempting to enter the market immediately upon expiry of the original term of the enantiomer patent. On the other hand, this increased vulnerability may be a point of negotiation for licensees considering terms and conditions.
Claims to dosage forms should be carefully drafted to ensure that they cover only useful dosages or, at the very least, a dependent claim should be included which is restricted to a narrow range of doses which the patentee can confidently argue are effective.
Lundbeck have applied for a stay of the order, pending an application for special leave to the High Court. This may provide an interesting sequel.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.