Introduction
On 11 June 2009, the Full Court of the Federal Court of Australia released its decision in Lundbeck v Alphapharm.1 This was an appeal from the decision of a single judge of the Federal Court handed down in June 20082 and the outcome had been eagerly awaited by those with an interest in the Australian pharmaceutical industry.
Separate substantive written reasons were delivered by Justices Emmett and Bennett. Justice Middleton substantially agreed with the written reasons of Justice Bennett.
This article considers a number of the key issues considered in the appeal, namely:
- whether the extension of term of the patent should be revoked, and
- issues of patent claim construction, patent validity and infringement.
In summary, the Full Court upheld the revocation of the extension of term of the patent. The product claims in question were held, by majority, to be valid, however the construction given to these claims is arguably narrower than that applied at first instance. Finally, the Full Court overturned the determination by the primary judge that Alphapharm infringed a method of manufacture claim based on a ‘pith and marrow’ test for infringement that is in contrast to the standard test of infringement generally accepted by Australian courts.
Enantiomers and racemates
The appeal concerned Lundbeck’s patent for a product known as ‘Escitalopram’, one of the two enantiomers of citalopram, and processes for its preparation.
Prior to considering the issues of this case, it is instructive to briefly review what an enantiomer is. Two chemical compounds may possess the same atomic components but a different spatial arrangement of those components. A special relationship is observed when two such compounds are also related by being non-superimposable mirror images of one another. An analogy often employed to assist in visualising this concept is a person’s left and right hand—each is a mirror image of the other, but they cannot be superimposed. Compounds that are related in this manner are referred to as a pair of enantiomers.
Enantiomers possess essentially identical physical and chemical properties. One notable difference in the properties of a pair of enantiomers is that when plane polarised light is passed through a purified enantiomer, one enantiomer will rotate the light to the right and the other will rotate it to the left. This difference results in the naming of enantiomers as (+) or (-), depending upon the direction of rotation. Escitalopram is the (+) enantiomer of citalopram. A mixture consisting of equal amounts of two enantiomers is known as a racemic mixture, or a racemate. A racemate will not rotate plane polarised light. This explanation is necessary in order to follow some of the Full Court’s reasoning.
It is common for pharmaceutically-relevant molecules to exist as different enantiomers, and it is also common for one enantiomer to have a higher or different pharmaceutical activity than its corresponding ‘mirror image’ enantiomer.
Factual background
Escitalopram is a selective serotonin reuptake inhibitor (SSRI) used in the treatment of major depressive disorder.
The following table summarises the key dates relevant to the appeal:
| Date |
Event |
| 5 January 1977 |
Priority date of Lundbeck’s Citalopram (citalopram racemate) patent (16 year term). |
| 13 June 1989 |
Priority date of Lundbeck’s Escitalopram (the (+) enantiomer) patent (20 year term). |
| 29 December 1997 |
First ARTG approval for Lundbeck’s Cipramil (containing the citalopram racemate). |
| 16 September 2003 |
First ARTG approval for Lundbeck’s Lexapro (containing the escitalopram enantiomer). |
| 22 December 2003 |
Lundbeck applied for an extension to the term of the Escitalopram patent by reference to the date of ARTG approval of Lexapro. |
| 27 May 2004 |
The Australian Patent Office granted Lundbeck an extension of term for the Escitalopram patent (from 13 June 2009 to 13 June 2014). |
| 15 June 2005 |
Alphapharm applied to register its generic version of escitalopram on the ARTG. |
| 19 May 2006 |
The Australian Patent Office reduced the expiry date of the extended patent term for the Escitalopram patent (from 12 June 2014 to 9 December 2012), after Alphapharm brought the earlier ARTG registration for Cipramil to its attention. |
| 24 April 2008 |
Decision at first instance handed down by the primary judge finding claims 1, 3 and 6 valid and infringed, claim 5 invalid and ordering that the patent term extension be removed (the patent to expire on 13 June 2009). |
Patent term extension issues
Part 3 of Chapter 6 the Patents Act 1990 (Cth) provides a mechanism for a patentee to apply for an extension of the term of standard patents relating to pharmaceutical substances.
The provisions are intended to allow for an extension of the patent term in cases where the process of obtaining registration of a pharmaceutical substance in the Australian Register of Therapeutic Goods (ARTG) has taken more than five years. The provisions in effect compensate the patentee for its inability to exploit the patented invention during that pre-registration period.
In order to obtain an extension, the following provisions must be satisfied:
- one or more pharmaceutical substances per se must be disclosed in the patent specification and its claim or claims
- goods containing, or consisting of, at least one of those pharmaceutical substances must be registered on the ARTG
- the period beginning on the date of the patent, and ending on the ‘first regulatory approval date’ for the substance (relevantly defined as ‘the date of the first inclusion in the ARTG of goods that contain, or consist of, the substance’), must be at least five years; and
- the application for an extension of the patent term must be made within six months of the later of the date of the first inclusion in the ARTG of goods that contain, or consist of, the substance, and the date the patent was granted.
As noted in Table 1 above, Lundbeck initially obtained a five-year extension of the patent term for its Escitalopram patent by reference to the ARTG registration of Lexapro. However, the Australian Patent Office subsequently decided to reduce the length of the patent term extension when it became aware of the earlier ARTG registration for Cipramil.
The matter came to be heard by Justice Lindgren of the Federal Court when Lundbeck appealed from that Patent Office decision to reduce the term of the extension. Justice Lindgren (the primary judge) upheld the Patent Office decision to the effect that Lundbeck was only entitled to an extension of term of its Escitalopram Patent by reference to the registration of Cipramil on the ARTG. However, because the time for making an application for a term extension based on Cipramil had passed, no extension of term was available with the consequence that the Escitalopram patent would expire on 13 June 2009.
On appeal to the Full Court, Justice Emmett, having found earlier in his written reasons that claims 1 to 5 were invalid, considered that the question of patent term extension did not arise for determination by him. However, his Honour did go on to say that if the issue did arise, he would be disposed to accept the primary judge’s conclusions as correct and that the patent would expire on 13 June 2009.
In her Honour’s written reasons, Justice Bennett spent more time reviewing the semantic arguments put before both the Federal Court and on appeal to the Full Court. As noted above, Justice Middleton agreed with Justice Bennett’s reasons.
One aspect considered by Justice Bennett was whether the expression ‘
per se’ in the first provision carried over into the other provisions despite not expressly appearing in them. Lundbeck’s interest in having the expression carry over to the other provisions was because Cipramil contains a different pharmaceutical substance
per se, the racemate, and the ARTG registration for Cipramil is therefore irrelevant for the purpose of an application for a patent term extension for the Escitalopram patent. Justice Bennett rejected Lundbeck’s submissions and summarised the relevant enquiries to be:
- the identification of a candidate patent for extension where the pharmaceutical substance per se is in substance disclosed and in substance within the scope of a claim, and
- identification of whether that pharmaceutical substance is contained in goods on the ARTG by simple comparison of the pharmaceutical substance with the ingredients of the goods on the ARTG (without consideration of the effectiveness or purity of the pharmaceutical substance in the goods on the ARTG).
Justice Bennett described as ‘compelling’ the primary judge’s reasoning that the word ‘contain’ in the provisions should be given its plain meaning and not import consideration of the therapeutic efficacy of the pharmaceutical substance in the goods on the ARTG.
Interestingly, Justice Bennett did not endorse the primary judge’s finding that it would be sufficient that Cipramil contained Escitalopram only ‘non-essentially or incidentally’, instead preferring to reserve her position on what the result would be of de minimis inclusion of the pharmaceutical substance in the goods on the ARTG. This did not arise as an issue to be determined on the facts of this case because the Citalopram racemate was made up of equal parts of the two enantiomers.
The Full Court held that Cipramil was the relevant registration on the ARTG for the purpose of any term extension for the Escitalopram patent. However, the time to make an application for an extension of term based on the ARTG registration of Cipramil had long since expired. As a consequence, there could be no extension to the term of Lundbeck’s Escitalopram patent, with the result that it is due to expire on 13 June 2009.
This aspect of the Full Court’s decision suggests that it may be difficult to obtain an extension of the term of a patent which relates to a ‘purified’ version (such as an isolated enantiomer) of an earlier ‘mixed’ or ‘impure’ pharmaceutical product (such as a racemate).
Construction of Claim 1
An issue to be determined by the Full Court was the proper construction of Claim 1 of the patent.
Claim 1 of the patent claims the (+)-enantiomer of citalopram, namely Escitalopram, and non-toxic acid addition salts thereof. The issues identified by Justice Bennett were whether Claim 1 was relevantly limited to:
- purified or isolated Escitalopram
- Escitalopram either alone or as part of a mixture, or
- Escitalopram as present in the racemate.
At trial, the primary judge held that as at the priority date of the patent, the skilled addressee would have understood that Claim 1 referred to purified or isolated Escitalopram, and not as part of the racemate or any other mixture. Further, the primary judge concluded that Claim 1 referred to Escitalopram that is at least 95 per cent pure, on the basis of general conventions understood by chemists.
Alphapharm appealed against this decision, arguing that the decision of the primary judge erroneously added three additional integers to Claim 1 that were not expressly included, namely:
- the limitation of ‘independently existing’ in relation to the (+)-enantiomer
- the degree of 95 per cent purity, and
- the type of purity referred to.
In the Full Federal Court, Justice Bennett construed Claim 1 to refer to isolated Escitalopram, but found that Claim 1 contained no quantification of the level of purity of Escitalopram claimed. Furthermore, Justice Bennett considered that no qualification of the type of purity should be imported as none was made clear in the specification. This interpretation of the Claim 1 (and dependent claims) suggests that impure Escitalopram is within the claims of the patent.
In considering this part of the appeal Justice Bennett held that the following principles apply when construing a claim:
- the words in a claim should be read through the eyes of a skilled addressee in the context in which they appear
- words used in a specification are to be given the meaning which the skilled addressee would attach to them, having regard to their own general knowledge and what is disclosed in the specification
- the construction of a specification, including the claims, is ultimately a question of law for the court
- it is not permissible to read into a claim an additional integer or limitation to vary or qualify the claim by reference to the body of the specification, and
- terms in the claim which are unclear may be defined by reference to the body of the specification.
Justice Bennett held that the primary judge was entitled to accept that the skilled addressee would read Claim 1, in the context of the whole specification, as referring to the isolated Escitalopram enantiomer, rather than the Escitalopram enantiomer as present in the racemate or otherwise in a mixture with the (-)-enantiomer. This was on the basis that the purpose of the (+) or (-) symbols was to distinguish the two enantiomers from each other, and also from being part of the racemate or any other mixture. Particular reference was made to the title of the patent, ‘(+)-Enantiomer of Citalopram and process for the preparation thereof’. In this context, the use of the (+) symbol implies that it is a reference to the (+)-enantiomer, Escitalopram, as distinct from that enantiomer as part of the racemate.
Justice Middleton, while agreeing with Justice Bennett, noted that the conclusion that Claim 1 refers to the isolated (+)-enantiomer does not involve impermissibly adding integers to Claim 1, but rather that it is implicit in the manner in which Claim 1 is worded, and the title of the patent.
In relation to the issue of purity, Justice Bennett held that in the absence of a qualification as to purity specifically expressed in the patent, none should be inferred. To this extent, Justice Bennett held that the primary judge erred in inserting an integer requiring 95 per cent purity.
In dissent, Justice Emmett concluded that in the absence of ambiguity in relation to Claim 1, there was no reason to apply anything other than a literal interpretation of Claim 1. As a result, Justice Emmett considered that Claim 1 simply related to the product or substance, the (+)-enantiomer, however it occurred, and there was nothing to suggest that it was to be isolated or of a particular purity. Accordingly, Claim 1 would extend to the (+)-enantiomer as part of the racemate or any other mixture.
Novelty
Justices Bennett and Emmett considered the issue of novelty from their differing perspectives on the construction of Claim 1. In particular they considered whether the Citalopram Patent, which disclosed the racemate, sufficiently disclosed the (+)-enantiomer so as to deprive the claims of the later Escitalopram patent of novelty.
At first instance and in light of the decision reached in relation to the construction of Claim 1, the primary judge had held that the product claims were valid, since there was no ‘enabling disclosure’ at the priority date that would point unmistakeably to the (+)-enantiomer, Escitalopram, as distinct from the racemate. This was on the basis that in 1988 (the relevant priority date) separating racemates was uncommon, difficult and expensive. In addition, since Citalopram was already highly effective, there was little motivation to try to resolve it into the separate enantiomers. Alphapharm appealed this decision.
Justice Bennett (with whom Justice Middleton agreed) dismissed this part of the appeal and upheld the findings of the primary judge. In doing so, Justice Bennett reviewed and discussed at length the applicable authorities in relation to anticipation and enabling disclosure. In summary, Justice Bennett concluded that:
- For the purposes of disclosure, the prior art must disclose an invention which, if performed, would necessarily infringe the patent.
- Where the prior publication is of the subsequently claimed invention, this is sufficient.
- If the prior disclosure falls short of complete disclosure, the question of sufficiency arises and the court must determine whether the prior disclosure is sufficient to enable the skilled addressee to perceive, understand and, where appropriate, apply the prior disclosure necessarily to obtain the invention.
- Disclosure of a racemate does not necessarily amount to disclosure of the individual enantiomers. Rather, this depends on the disclosure in the context of the prior art document.
- The enabling disclosure in the context of a product claim means that the earlier disclosure must point unmistakably to the enantiomer as distinct from the racemate.
Applying these principles to the alleged prior disclosure in the Citalopram patent, Justice Bennett held that the description of the racemate in the Citalopram patent did not constitute an anticipation or enabling disclosure of Escitalopram, and therefore did not render Claim 1 (and dependent Claims 2, 3, 4 and 5) of the patent invalid, on the basis of a lack of novelty. This was on the basis that:
- the skilled addressee would have been able to identify the formula of each enantiomer of Citalopram, and understood that one of these enantiomers would be (+), the other (-)
- however, the skilled addressee would not have known in the absence of experimentation which of the enantiomers was (+) and which was (-)
- there was nothing telling the skilled addressee to resolve the racemate into the separate enantiomers – there were no clear and unmistakable directions to obtain the enantiomers, and
- the Citalopram patent was silent as to the method of resolving the racemate into the enantiomers, and there were numerous methods available
Accordingly, the Citalopram patent did not disclose something which, if performed, would necessarily infringe the patent.
Again in dissent, Justice Emmett concluded that Claim 1 (and its dependent claims) were not novel as at the priority date, on account of the prior disclosure of each of the enantiomers in the Citalopram patent. This was the result of Justice Emmett’s interpretation that Claim 1 was not limited to the isolated (+)-enantiomer. On this view, the disclosure of the racemate in the Citalopram patent disclosed and clearly anticipated each of the enantiomers.
Infringement
Alphapharm appealed the finding that it infringed Lundbeck’s method of manufacture claim by using a bromo-diol compound instead of the cyano-diol compound required in the claim. The primary judge’s finding that Alphapharm infringed this claim because it had taken the ‘pith and marrow’ of what had been claimed, despite Alphapharm’s process not falling literally within the claim, was one of the most surprising aspects of the primary judge’s decision. That approach represented a departure from the approach taken by Australian courts over recent decades and generated considerable uncertainty in determining the scope of a patent claim.
The Full court unanimously overturned this aspect of the primary judge’s decision. The Full Court relied on the patentee’s inclusion of the specific formula for the cyano compound in the chemical structure of the cyano-diol to find that the cyano-diol was an essential integer of the method of manufacture claim. Given that the cyano-diol was an essential integer of the claim, the use of a similar method involving substituting the cyano-diol with a bromo-diol did not infringe the claim.
The Full Court did not reconsider whether Alphapharm had infringed Claim 1, 3 and 5 in view of the different construction given to Claim 1. It appears that Alphapharm accepted that if Claim 1 was valid it was infringed.
Clarity
Justice Bennett found that there was no lack of clarity, or degree of uncertainty, arising from her interpretation of Claim 1. Further, despite disagreeing with the primary judge’s acceptance of a limitation of at least 95 per cent purity of the separated or isolated (+)-enantiomer in Claim 1, Justice Bennett found there was no error on the part of the primary judge in finding there was no lack of clarity or failure to define.
Utility
The primary judge concluded that a claim to a dosage form where Escitalopram was present in an amount from 0.1 to 100mg per unit dose lacked utility for including quantities outside of the range of 5mg–40mg shown by the evidence to be the minimum to maximum dosage range. Justice Bennett found that this conclusion was open to the primary judge on the available evidence, and that Lundbeck had not established any error on the part of the primary judge and the primary judge’s ruling stood.
What next?
The day after the appeal decision was handed down, the Full Court granted Lundbeck a stay of the order for removal of the patent term extension from the Register pending the outcome of Lundbeck’s foreshadowed application for special leave to appeal to the High Court.
There may well be another chapter in this story.
This article was written by Patrick Sands, Senior Associate and Louise Dumbrell, Solicitor, Melbourne and Anna Vandervliet, Solicitor, Sydney.
Endnotes
1. H Lundbeck A/S v Alphapharm Pty Ltd [2009] FCAFC 70.
2. Alphapharm Pty Ltd v H Lundbeck A/S [2008] FCA 559.
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