IP Alert June 2009

Full Federal Court clarifies test for novelty concerning patents for enantiomers

There is something for everyone in the majority decision of the Full Federal Court on Alphapharm’s appeal in its fight with Lundbeck over Lundbeck’s patent for the antidepressant drug escitalopram. The majority of the Full Court largely upheld the primary judge’s findings on validity and infringement, clarifying the test for novelty along the way, but also upheld the finding that the term of Lundbeck’s patent was not properly extended.

On the one hand, the decision supports the ability of patentees to obtain and enforce patents for specific enantiomers. On the other, generic drug manufacturers will recognise the significance of practical difficulties for patentees in obtaining extensions to such patents.

At first instance, Alphapharm Pty Ltd sought revocation of Lundbeck A/S’s Australian Patent No. 623144 (the Patent) on the grounds that it lacked novelty, inventive step, definition, fair basis, clarity, utility and was not a manner of manufacture. It also sought an order that the Register of Patents be rectified to remove the record of the extension of the term of the Patent.

Lundbeck and its exclusive Australian licensee, Lundbeck Australia Pty Ltd, cross-claimed against Alphapharm for infringement.

In Alphapharm Pty Ltd v Lundbeck A/S [2008] FCA 559, Justice Lindgren of the Federal Court found that certain claims were valid, and that Alphapharm had infringed the Patent. His Honour found that claim 5 of the Patent was invalid for inutility.

On the issue of the extension of the patent term, Lindgren J held that citalopram “contains” escitalopram, since citalopram is a racemic mixture comprising of escitalopram in the amount of 50%. As a result, the time limit for applying for an extension of the patent term was triggered when citalopram was first listed on the Australian Register of Therapeutic Goods (ARTG). Lundbeck’s application for extension had been made outside the statutory six month period from the inclusion of citalopram on the ARTG, and accordingly the extension that had been granted by the Commissioner was held invalid.

The Federal Court’s findings in respect of validity and the patent term also applied in respect of similar proceedings brought by Arrow Pharmaceuticals.

The Patent claims the antidepressant drug escitalopram (a single enantiomer of citalopram), pharmaceutical compositions containing escitalopram and a method of preparing escitalopram. Escitalopram is the S-enantiomer or (+)-enantiomer of the compound citalopram, which is also used to treat depression. Citalopram itself is a chiral molecule, also patented by Lundbeck under Australian Patent No. 509445 (the Citalopram Patent). Citalopram is a racemic mixture comprising two enantiomers, escitalopram (i.e. (+)-citalopram)) and (-)-citalopram, in a 50:50 mixture.

The Patent was filed on 13 June 1989 with a priority date of 14 June 1988. The 20 year term of the Patent was due to expire on 13 June 2009. Following an application by Lundbeck for a term extension under section 70 of the Patents Act 1990 (Cth), the Commissioner initially granted an extension to 13 June 2014.

Alphapharm appealed the findings on validity and infringement. It was largely unsuccessful on this front.

The majority decision of the Full Federal Court in H Lundbeck A/S v Alphapharm Pty Ltd [2009] FCAFC 70, considered the meaning of “enabling disclosure” with respect to novelty and clarified the Australian test for novelty. In particular, the Full Federal Court agreed that certain claims of the Patent were valid and that Alphapharm had infringed, although it disagreed with the primary judge to the extent that he thought Alphapharm had infringed one of the method claims. The Full Federal Court upheld the finding of the primary judge that claim 5 of the Patent was invalid for inutility and that it should be revoked, together with the finding that the Patent expired on 13 June 2009.

Construction of the Patent

The Full Federal Court held that the primary judge was entitled to accept the evidence that the skilled addressee would read claim 1 as referring to the isolated (+)-enantiomer. The Full Federal Court did not accept Alphapharm’s contention that claim 1 was a reference to the (+)-enantiomer as present in the racemate or in a mixture with the (-)-enantiomer.

However, it did not agree with the primary judge that the skilled addressee could import a measure of purity into claim 1. In particular, the Full Federal Court did not accept that the convention of at least 95% purity could be attributed to the reference of the (+)-enantiomer in claim 1 of the Patent.

Novelty

The Full Federal Court clarified the test for novelty, and in doing so cautioned that care must be taken in applying United Kingdom jurisprudence to Australian patents. In particular, it noted that the primary judge had incorrectly applied the concept of “enabling disclosure” in considering the novelty of the product claims, stating that an enabling disclosure: “must point unmistakably to the (+)-enantiomer of citalopram, as distinct from the racemate as a drug desirable to obtain.” The primary judge had found that the Citalopram Patent did not expressly or impliedly disclose the individual enantiomer, and that the relevant prior art taught away from the invented product because it suggested that the R-enantiomer rather than the S-enantiomer could be expected to be more potent. Thus the primary judge found that the prior disclosure of the racemic mixture was not an anticipation of the single (+)-enantiomer.

Although the Full Federal Court upheld the novelty of claims 1, 2, 3, 4 and 5 of the Patent and agreed with the conclusion of the primary judge on the question of novelty, it did not agree that claim 1 was limited to the enantiomer as a drug desirable to obtain or otherwise. In reaching its decision, the Full Federal Court found that the Citalopram Patent did not anticipate the Patent because although the skilled addressee would have understood that citalopram consisted of the (+) enantiomer and the (-)-enantiomer, he/she would not have known, without further experimentation, which was the (+) enantiomer and which was the (-)-enantiomer.

Utility

The Full Federal Court upheld the conclusion of the primary judge that claim 5 failed for inutility. The invention disclosed in claim 5 was not patentable because the claimed range of 0.1 to 100 mg per unit dose spanned quantities well below the useful minimum dose of 5mg and above the useful maximum dose of 40 mg.

Infringement

Lundbeck contended that Alphapharm had infringed and threatened to infringe claims 1, 3 and 5, which are product claims, and claim 6(b), which is a method claim. However, the Full Federal Court upheld the Federal Court’s finding that claim 5 was invalid. Alphapharm accepted that it infringed claims 1 and 3, but successfully appealed the primary judge’s finding that it had infringed claim 6(b) of the Patent.

Claim 6(b) is for a 3-step method of preparing escitalopram. Alphapharm argued that the method it uses departs from the method disclosed by claim 6(b) in that it involves use of a bromo-diol rather than the cyano-diol. The Full Federal Court held that if the method disclosed by claim 6(b) was to be interpreted as being confined to use of the cyano-diol, represented by the symbol “NC”, the symbol “R” could have been substituted in place of the symbol NC. Claim 6(b) of the Patent does not use “R” symbol, thus the cyano-diol is an essential integer of the method disclosed in claim 6(b). Thus, the Full Federal Court found that a method that involved substitution of the bromo-diol for the cyano-diol does not infringe the method disclosed by claim 6(b).

Extension of term

Section 70 of the Patents Act 1990 allows for an extension of term for a standard patent under certain conditions in recognition of the delay in exploiting a patent due to obtaining listing of the relevant goods on the ARTG under the Therapeutic Goods Act 1989. The Patent had originally had its term extended by the Commissioner for Patents for 5 years to 13 June 2014 on the basis that the first regulatory approval of escitalopram (marketed as Lexapro) had occurred on 16 September 2003.

However, the majority of the Full Federal Court agreed with the primary judge finding that citalopram (marketed as Cipramil) contained escitalopram since citalopram, despite being a racemic mixture, contained escitalopram molecules. Accordingly, Lundbeck could only base an extension of term application on the date of inclusion of Cipramil on the ARTG which was 9 December 1997 (i.e. the first regulatory approval date). Lundbeck’s application for an extension was made in December 2003, well outside the statutory 6 month period since the ARTG listing of Cipramil. **

Conclusion

The decision significantly strengthens the ability of potential patentees to obtain patents for specific enantiomers. Arguably, this approach rewards the high risk pathway of separating and analysing various enantiomers and, potentially, other types of high risk research and development. Viewed in this light, the decision is a positive outcome for the innovators.

However, while the decision is a win for the patentee in terms of validity, the construction of section 70(3)(a) of the Patents Act (and, by implication, section 70(5)(a) of the Patents Act) is a positive step for the generics as it imposes practical limitations on the availability of extensions to the patent term. In particular, where an extension of term is sought for a drug, and one or more pharmaceutical substances per se within that drug are already included on the ARTG, the first regulatory approval date will be taken to be the day the relevant pharmaceutical substance was first included on the ARTG.

Innovators may now face some very real practical problems attempting to stave off the generics by seeking an extension of the term of patents for specific enantiomers following the expiry of the initial 20 year term of such patents.

** Note: A stay has been imposed on the order removing the extension of term for Escitalopram (Lexapro) pending any appeal by Lundbeck to the High Court.