Eli Lilly and Company Limited v Apotex Pty Ltd [2013] FCA 214

The Federal Court has upheld the validity of Eli Lilly’s Australian patent covering anti-psychotic drug olanzapine in a recent revocation action, with Apotex failing on all grounds.

Olanzapine, marketed under the name ZYPREXA®, has enjoyed significant commercial and therapeutic success in the treatment of schizophrenia and bipolar disorder. Given the commercial success, it was perhaps unsurprising that generic pharmaceutical manufacturer Apotex took steps to market their own generic olanzapine pharmaceuticals. Although Apotex succeeded in securing marketing approval from the Therapeutic Goods Administration (TGA) in November 2009 (involving registration of its generic products on the Australian Register of Therapeutic Goods (ARTG)), it was restrained from marketing its products pending the outcome of proceedings brought by patentee Eli Lilly to determine whether Apotex's intended action would infringe Eli Lilly’s patent rights. Apotex concurrently made a cross claim for revocation. In unusual circumstances, the Patents Act 1952 applied to considerations of validity while the Patents Act 1990 applied to the issue of infringement, due to the respective dates of filing and grant of the patent in suit.

Eli Lilly's earlier patent not an anticipation

Eli Lilly’s olanzapine patent family included an earlier patent to a broad class of benzodiazepines. While olanzapine fell within the scope of the earlier broad disclosure, it was not explicitly disclosed in the earlier patent. Accordingly, Eli Lilly subsequently pursued and was granted a patent of narrower scope that was directed to olanzapine per se. Apotex cited Eli Lilly's earlier patent, containing the broad disclosure of the class of benzodiazepines, against the later patent in suit on grounds of novelty. While Justice Middleton considered the principles governing selection patents in this instance, they were not applied in reaching a decision on novelty. On this issue, the Court applied the general principles of novelty; finding that even though olanzapine is encompassed within the broad scope of the earlier patent, the earlier disclosure failed to provide clear and unmistakeable directions, and thus did not constitute an anticipation of the later claim.

Ambiguous prior art failed to provide clear and unmistakeable directions

In addition to the earlier patent, a 'note' published in the East German journal Die Pharmazie in 1983 was also considered for purposes of novelty. However, the title of the Die Pharmazie publication and the structures of the compounds reported therein, were inconsistent. In considering whether the Die Pharmazie publication anticipated olanzapine it was necessary for The Court to first resolve this inconsistency.

The Die Pharmazie publication cited two earlier publications. Upon reference to the two earlier citations, it was apparent that the Die Pharmazie publication in fact contained two errors in the structures of the compounds depicted therein, and had intended to refer to the structurally related compound flumezapine instead of olanzapine. The errors included i) the depiction of a piperidine ring rather than a piperazine ring, and ii) the omission of a fluorine on the benzene ring. Nevertheless, it was submitted that in the event a person skilled in the art proceeded to correct one of the two errors (the nitrogen in the piperazine ring), then this may lead to the identification of olanzapine.

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The Court however considered that because of the inherent ambiguity or lack of reliability in the eyes of the skilled addressee, the Die Pharmazie publication could not be considered to provide clear and unmistakeable directions to adopt the invention as claimed. As an alternative, Middleton J suggested that it was a reasonable and prudent step for the skilled addressee to refer to the earlier citations to resolve the ambiguity. However, in so doing, the skilled addressee would note that the compound referred to was in fact flumezapine, which would further confirm the unreliability of the Die Pharmazie publication. On either approach, the Die Pharmazie publication did not constitute an anticipation of the later claim.

Impermissible to disregard olanzapine's utility in considering inventive step

The Patents Act 1952 in a new window (via AustLII / ComLaw)" target="_blank" rel="nofollow" class="citation" href="http://www.comlaw.gov.au/ComLaw/Management.nsf/lookupindexpagesbyid/IP200837281?OpenDocument">Patents Act 1952 was applied to considerations of inventive step, whereby a patent may be revoked if the invention does not involve an inventive step having regard to what was known or used in Australia on or before the priority date of the claim. At issue was the starting point from which obviousness should be considered. As the claims of the patent in suit were not limited to any particular therapeutic use, Apotex submitted that it was sufficient to demonstrate that olanzapine lacked inventiveness on its face. Accordingly, they argued that the correct starting point for consideration of inventive step was the structurally related compound flumezapine. However, Middleton J considered that it was impermissible to divorce olanzapine from its context and to subject it to an obviousness test that disregarded its utility. The Court held that structurally related flumezapine was not part of the common general knowledge in Australia at the priority date, and as such, was irrelevant to the question of inventive step. Furthermore, Justice Middleton highlighted that while the "problem-solution" approach was helpful, it should not be universally applied in determining the question of obviousness.

Olanzapine was the compound claimed, despite unconventional nomenclature

The issue of infringement and construction of the claims was also considered at length, as the claims of Eli Lilly's patent made reference to olanzapine by chemical name only, with no chemical structure appearing in the claim. However, the compound as claimed did not follow conventional International Union of Pure and Applied Chemistry (IUPAC) nomenclature, typically relied upon for the systematic naming of chemical compounds. It was agreed by all parties that the correct IUPAC name for olanzapine is 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine (Fig. 2A). The claims of the patent were instead directed to 2-methyl-10-(4-methyl-1-piperazinyl)-4H-thieno-[2,3-b][1,5]benzodiazepine (Fig. 2B).

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The question thus arose as to what was actually claimed. Apotex contended that the IUPAC name is the only name which unambiguously describes the structure of olanzapine, and that there was no basis to extend to Eli Lilly what it might have intended to claim, rather than what the claim specifically recites.

Despite the ambiguity with regard to nomenclature, it was noted that throughout the specification the ambiguous chemical name was clearly associated with the correct chemical structure of olanzapine. The Court highlighted that the claims must not be construed in isolation, finding that a skilled person, based on the specification as a whole, would understand that olanzapine was the compound claimed.

Eli Lilly's patent valid on all grounds

Eli Lilly's patent was thus upheld on all grounds, with the Court determining that Apotex's intention to exploit olanzapine during the term of the patent would constitute infringement. It is of note that the patent in suit expired on 5 March 2012 and is no longer in force.