Alphapharm v Lundbeck per se

The Full Federal Court has dismissed yet another appeal in the Alphapharm v Lundbeck (escitalopram) saga:

You will recall that Lundbeck had applied (10 years late)[1] for an extension of the term of its escitalopram patent under s 70 of the Patents Act, escitalopram being the (+) enantiomer of citalopram.[2]

The issue in this appeal was whether escitalopram satisfied the requirement in s 70(2)(a) that:

one or more pharmaceutical substances per se must in substance be disclosed in the complete specification of the patent and in substance fall within the scope of the claim or claims of that specification

Alphapharm’s argument was that Lundbeck’s patent was a claim to a pharmaceutical substance – the isolated or pure enantiomer – but it was not a claim to a pharmaceutical substance per se. Rather, Alphapharm characterised the claim as a claim to the substance limited by a requirement of purity of manufacture.

Bennett, Nicholas and Yates JJ rejected Alphapharm’s characterisation.

Claim 1 of the escitalopram patent is to:

(+)–1-(3-dimethylaminopropyl)–1-(4’-fluorophenyl)–1,3-dihydroisobenzofuran–5-carbonitrile and non-toxic acid addition salts thereof.

Their Honours pointed out that the claim did not itself use the word “isolated” or “pure”. Nonetheless, the skilled addressee would understand the claim to be referring to the substance constituted by the isolated enantiomer, not as existing in the racemate. That substance was a new chemical entity with different characteristics and properties to the racemate.

92 …. the claim is to the (+)-enantiomer and nothing else. The term “pharmaceutical substance per se” simply means the pharmaceutical substance “in itself”. In Boehringer, Heerey J observed that per se meant ‘by or in itself’ ‘intrinsically’ or ‘essentially’ (at [7]). The Full Court approved that approach on appeal (at [37]).

93 Semantics aside, it is clear that the claim describes a pharmaceutical substance per se. The substance was, as explained by Lindgren J at [536], a new chemical entity. The racemate and the (+)-enantiomer had different physico-chemical interactions manifested in different pharmacodynamics and pharmacokinetics (the Decision at [234]). The claim is to (+)-citalopram, irrespective of how it is produced. The isolated (+)-enantiomer plainly qualifies as a pharmaceutical substance per se and the primary Judge was correct in concluding that it satisfies s 70(2)(a) of the Act.

It looks like things are now getting down to the sharp pointy question of how much will have to be paid in terms of pecuniary remedies. As this was an appeal from a single judge who, in turn, was hearing an appeal from the Commissioner, Alphapharm needed leave to appeal.[3] While cases granting “leave” are not quite as rare as hen’s teeth, the Full Court noted leave should be granted because:

35 This application also represents Alphapharm’s only course in challenging the extension of term of the Patent, which has significant consequences to Alphapharm. If Lundbeck is successful, the term of the Patent will be extended and Lundbeck’s infringement proceedings against Alphapharm can proceed.

Alphapharm Pty Ltd v H Lundbeck A/S [2015] FCAFC 138 (Bennett, Nicholas and Yates JJ)


  1. The High Court held that Lundbeck was not “out of time” in making its application last year.  ?
  2. Lundbeck patented the racemate citalopram in 1980 and marketed it in Australia as Cipramil. The racemate being a mixture of both the (+) and (-) enantiomers. Lundbeck marketed escitalopram as Lexapro.  ?
  3. Patents Act s 158(2).  ?

Patenting racemates and enantiomers

Lundbeck had a patent for citalopram for the treatment of depression, which it marketed in Australia under the name Cipramil

Citalopram is a chiral molecule: it can exist in two isomeric forms; a (+)-enantiomer and a (-)-enantiomer. The two forms have the same chemical structure, but they are mirror images. At its priority date, the relevant skilled addressees would have understood that the compound was a racemate or racemic mix consisting of both the (+)-enantiomer and the (-)-enantiomer.

Subsequently, Lundbeck discovered a way to make the (+)-enantiomer in isolated or pure form and, even better, it was this enantiomer that contributed the therapeutic effect of citalopram. It obtained a further patent, claim 1 of which was for:

1. (+)-1-(3-dimethylaminopropyl)-1-(4’-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile and non-toxic acid addition salts thereof.

The Full Federal Court by 2-1 (Bennett and Middleton JJ; Emmett J dissenting) has upheld the validity of this claim in the face of the prior patent for citalopram.

If resort could be made to the body of the specification, it was clear that the skilled addressees would have understood that claim was a claim to the enantiomer in its pure, isolated form and not to the product as part of a racemic mix.

Emmett J considered the claim was clear and unambiguous. Accordingly, there was no warrant to resort to the body of the specification.  Bennett and Middleton JJ, on the other hand, accepted that the trial judge was entitled to accept evidence about how the skilled addressee would have read the claim.  Bennett J approved the approach taken by Dr Barker, as delegate for the Commissioner, in Emory University v Biochem Pharma:

[152] …. He drew a distinction between a reading of the claim in the context of the specification to understand what the claim is talking about (as did Burchett J in International Business Machines Corporation v Commissioner of Patents [1991] FCA 625; (1991) 33 FCR 218), where the whole thrust of the specification makes a limitation clear, and impermissibly importing a limitation from “mere comments” in the description. ….

Her Honour further explained that the citalopram patent didn’t anticipate the claim:

193 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. As the primary judge pointed out at [171], 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. As his Honour said, 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.
194 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.

193 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. As the primary judge pointed out at [171], 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. As his Honour said, 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.

194 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.

That seems rather to qualify the force of the earlier point. One might even think, with respect, that it limits the patentable subject matter to some particular method of making the purified, isolated (+)-enantiomer, rather than the substance per se.

In contrast to this approach, however, Lundbeck lost its attempt to get the term of the second, escitalopram patent extended pursuant to s 70 of the Patents Act.

The problem for Lundbeck here was that s 70(2) referred to a patent for a pharmaceutical substance per se, but s 70(3) and (5) and s 71 did not. The Full Court found that s 70(2) operated to identify the subject matter of the extension application – the substance per se here being escitalopram.

Because the later sub-sections did not refer to the substance per se, when it came to working out the timing for making the application for an extension of term, the question was (in this case) the date when goods containing the substance (not the substance per se) were first included in the Australian Register of Therapeutic Goods.

Citalopram, of course, contained the (+)-enantiomer and it had been registered in the ARTG. It was first included in the ARTG on 29 December 1997. The application to extend the term of the escitalopram patent was made almost 6 years later – on 22 December 2003.

Section 71(2), however, required the extension application to be made within 6 months of the patent being granted or “the date of commencement of the first inclusion in the [ARTG] of goods that contain … the pharmaceutical substance referred to in s 70(3)” (i.e., within 6 months of the inclusion in the ARTG of citalopram).

The majority also found that claim 5 was invalid for insufficiency. However, Lundbeck did succeed insofar as Alphapharm was found to have infringed claims 1 and 3 of the escitalopram patent, presumably up to the date of expiry of the patent on 13 June 2009.