Generic Health succeeds in invalidating patent for aripiprazole: Otsuka Pharmaceutical Co., Ltd v Generic Health Pty Ltd (No 4)  FCA 634
Generic Health is perhaps a step closer to bringing its generic version of the antipsychotic drug aripiprazole to market in Australia after Justice Yates struck down one of Otsuka’s patents for the drug. Although it’s unclear whether the path has been cleared for the launch of generic aripiprazole, Justice Yates’ decision – which found that key claims of the patent lacked novelty and were obvious – will be of interest to generic pharmaceutical companies faced with follow-on patents for known pharmaceutical compounds.
Background to the proceedings
Proceedings were originally commenced by Otsuka in 2012, with the company alleging threatened infringement of two patents, the ‘752’ and ‘772’ patents. Otsuka was joined in the proceedings by Bristol Myers Squibb, the “exclusive licensee” of Otsuka’s patents for aripiprazole. (If you saw our post from earlier this year – available here – you would be aware that in related proceedings against a different generic company for infringement of a different aripiprazole patent, the Full Federal Court confirmed that BMS did not have standing to sue the generic company because BMS was not a true “exclusive licensee” according to the requirements of the Patents Act.)
Shortly after proceedings were commenced, Generic Health was enjoined from listing its generic products on the PBS, with Justice Yates finding that Otsuka had made out a prima facie case of threatened infringement of claim 7 of the 772 patent. This decision was upheld on appeal in March 2013.
At the final hearing in March 2014, Generic Health gave undertakings removing the need for the Court to consider infringement of the 752 patent and later gave notice that it no longer sought revocation of this patent. Accordingly, Justice Yates’ decision concerns the 772 patent only.
The 772 patent
The 772 patent reports the discovery that certain compounds – including aripiprazole – have agonistic activity at a particular serotonin receptor (the 5-HT1A receptor subtype) and are thus useful in treating disorders associated with this receptor.
Claim 1 of the patent claims the use of aripiprazole for the production of a medicament, effective in the treatment of disorders of the central nervous system associated with the 5-HT1A receptor subtype, in which the disorder (i) is selected from cognitive impairment caused by treatment-resistant schizophrenia or inveterate schizophrenia or chronic schizophrenia, and (ii) fails to respond to specified antipsychotic drugs.
Claim 7 of the patent claims a method for treating patients suffering from disorders of the central nervous system associated with the 5 HT1A receptor sub-type, in which the disorder (i) is selected from cognitive impairment caused by treatment-resistant schizophrenia or inveterate schizophrenia or chronic schizophrenia, and (ii) fails to respond to specified antipsychotic drugs, by administering a therapeutically effective amount of aripiprazole.
Justice Yates found that the disclosures of three prior art documents – each of which taught the use of aripiprazole for the treatment of schizophrenia – would have resulted in the treatment of cognitive impairment associated with a patient’s schizophrenia in the manner suggested by claims 1 and 7 of the patent.
Justice Yates agreed with Generic Health’s argument that it was not necessary for the prior art documents to teach an association between the 5-HT1A receptor subtype and the treatment of cognitive impairment in schizophrenia because such a requirement was simply information about how the drug worked:
The provision of information that certain of the then known symptoms of schizophrenia are also associated with the 5-HT1A receptor is really no more than an elucidation of the action of the known carbostyril compounds, including aripiprazole, in treating schizophrenia, and a contribution to knowledge of the possible aetiology of those particular symptoms. These accretions to knowledge, without more, do not provide novelty of invention. They are simply aspects of knowledge, albeit new information, about the then known therapeutic use (the treatment of schizophrenia) of a then known compound.
Justice Yates also agreed that the claimed invention was not directed to a new use of aripiprazole, but to the same use (albeit in the light of further information about how that use is achieved):
Properly understood, claim 7 of the 772 patent is directed to the use of aripiprazole to treat a subset of the symptoms of schizophrenia in certain patients on certain occasions, when it is already known that aripiprazole can be used to treat schizophrenia generally. Claim 7 merely partitions something that is old under the guise that the part it takes and claims as an invention is new. However, such an “invention” is not new. Claim 7 is not directed to a new therapeutic use, but an old one. The forms of cognitive impairment referred to in claim 7 were, at the priority date, but some of the known symptoms of schizophrenia. If, at that time, aripiprazole had been used in a therapeutically effective amount to treat schizophrenia, it would inevitably have treated cognitive impairment of the kind referred to in claim 7, including if used as third line or later line treatment in those patients whose symptoms had failed to respond to two or more of the antipsychotic drugs identified in the claim.
The Court’s findings on novelty suggest, therefore, that where there is a general disclosure that a drug can be used to treat a disease, this disclosure will necessarily be understood as teaching treatment of any sub-types or symptoms of that disease.
Justice Yates found claims 1 and 7 lacked an inventive step because the skilled addressee would have been directly led as a matter of course to try aripiprazole as a method of treatment, and they would have done so in the expectation that the drug might well be useful as a method of treatment as claimed. This conclusion was made based on the common general knowledge when read with two prior art documents which taught that aripiprazole could be used to treat patients with schizophrenia and that such treatment had beneficial results in treating cognitive impairment associated with schizophrenia.
His Honour held that it was not necessary for the prior art documents to further disclose the association between aripiprazole and the 5-HT1A receptor subtype (“[t]his discovery provides no more than an elucidation of why aripiprazole is useful”), or to further disclose that aripiprazole should only be used once patients have failed to respond to other antipsychotics (because the switching of medication in the treatment of schizophrenia was common general knowledge).
Justice Yates found that had the claims of the 772 patent been valid, Generic Health’s “GH Products”, registered for the treatment of schizophrenia, would have infringed claims 1 and 7.
His Honour found that claim 1 – which was a Swiss-type claim – would have been infringed directly. His Honour accepted the applicants’ argument that Generic Health’s intention to market and supply its products in Australia fell within the meaning of “exploit” in the Patents Act because the product produced by the claimed method or process would be exploited in Australia. Justice Yates held that that it did not matter if the method or process is performed outside Australia – it is enough if the resulting product is imported into Australia and subsequently exploited. Relevantly, the marketing approval and registration of the goods extended to encompass the claimed therapeutic uses. An undertaking offered by Generic Health not to promote the products for the therapeutic use defined in claim 1 was insufficient to avoid infringement because the products would still have the claimed therapeutic use irrespective of the way in which they are marketed.
His Honour also held that claim 7 would have been infringed indirectly through operation of s 117 of the Patents Act. His Honour found that:
- Generic Health’s products were not “staple commercial products”. His Honour emphasised that it is necessary to consider whether the allegedly infringing products – which in this case were the GH Products indicated for the treatment of schizophrenia – were staple commercial products, not aripiprazole per se.
- Generic Health had reason to believe its GH products would be put to a use that would infringe claim 7. His Honour found that, determined objectively:
…at least for some clinicians, switching (including, importantly, switching to aripiprazole even as third line or later line treatment) is, and would be, a realistic and legitimate option to treat the patient’s cognitive impairment associated with schizophrenia, where those problems persist…
…such treatment would extend, realistically, to the method of treatment claimed in claim 7, even though, in practice, such treatment might only be required for a relatively small proportion of patients being treated for schizophrenia.
Justice Yates’ decision, Otsuka Pharmaceutical Co., Ltd v Generic Health Pty Ltd (No 4)  FCA 634, is available here.