We recently published in Australasian Biotechnology (and on our website) on the nexus between IP and clinical trials in Australia, in which we highlighted the importance of balancing the timing and content of a patent application with the potential for novelty-destroying clinical trial disclosures and the need for supporting data. The recent Patent Office decision in Astellas Pharma Inc. v Aragon Pharmaceuticals, Inc. [2022] APO 36 (Astellas) further emphasises the importance of filing a patent application before publishing clinical trial information in Australia, where even untested hypotheses can put method of treatment and Swiss-style claims at risk of invalidity.

Background

The claims at issue in Astellas were directed to methods of treating non-metastatic castration-resistant prostate cancer (nmCRPC) by administering either apalutamide (ARN-509) or enzalutamide (MDV3100) in combination with a gonadotropin releasing hormone agonist or orchiectomy (collectively referred to as androgen deprivation therapy or ADT). The specification included the results of a phase II clinical trial in which men with nmCRPC were administered apalutamide. Relevantly, the specification did not explicitly state that those trial participants were also receiving ADT.

Several prior art documents were cited relating to apalutamide and enzalutamide clinical trials in patients with nmCRPC. The applicant argued that those documents also did not explicitly disclose that the clinical trial patients were administered apalutamide or enzalutamide in combination with ADT.

Implicit disclosure of combination therapy

In assessing whether any of the cited prior art documents provides “clear and unmistakeable directions” to perform the claimed methods in accordance with the General Tire test,[i] the Delegate noted:

For the purposes of assessing novelty the General Tire test is quite strict: if a citation could be read in a way that does not infringe the patent then it is not anticipatory. For the Applicant’s case to succeed it is merely necessary to establish that the skilled addressee could read each disclosure such that the patients in the trials are not receiving ADT.

In other words, the claimed invention must be the inevitable result of following the teaching of the prior art in order to be anticipated. In that respect, the Delegate concluded based on expert evidence that “the skilled reader would have implicitly understood that patients with relapsing (i.e. castration resistant) prostate cancer should be receiving ADT, particularly those participating in clinical trials”.

Clinical efficacy not required to anticipate “method of treatment” claims

The Applicant contended that “in order to be novelty-defeating, the prior art must disclose that the therapeutic effect would be achieved”. In doing so, the Applicant sought to distinguish its “method of treatment” claims from the “method for treatment” claims at issue in Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd [2020] FCAFC 116 (Mylan), in which the Full Federal Court found that a reasoned yet untested clinical trial hypothesis was sufficient to anticipate the method for treatment and Swiss-style claims (see our articles on the decision here and here).

The Delegate considered the factual circumstances in Astellas to be similar to those in Mylan and concluded there was no basis in law that a therapeutic effect must be achieved in order for a method of treatment claim (or Swiss-style claim) to be anticipated; what is relevant is the therapeutic purpose.[ii] This contrasts with the approach of the UK courts, which require disclosure of a therapeutic effect in order for purpose-limited product claims (EPC 2000 style “for use” claims) or Swiss-style claims to be anticipated.[iii]

The Delegate also did not consider there to be any meaningful distinction between “methods of treatment” and “methods for treatment” that would allow for an alternative finding to that reached by the Full Court in Mylan.

Between a (novelty) rock and a (support) hard place

The Opponent contended that if the claims were novel because the prior art does not disclose ADT, they necessarily lacked support because the specification at best provided the same level of disclosure in relation to the clinical trial as the prior art. The Delegate agreed, noting:

…the only clinical example in the specification does not disclose the presence of ADT, so if the skilled reader would not have recognised the presence of ADT in the citations then they could hardly be said to have read it in to the example in the specification.

Thus, while the tests for novelty / implicit disclosure and lack of support are different, applicants can find themselves between a rock and a hard place when evidence in support of external invalidity (i.e., a lack of novelty or inventive step) is the same evidence required to establish internal validity (i.e., support or enablement).

Key takeaways

The Astellas decision further highlights the importance of filing a patent application before disclosing information about clinical trials to avoid potential novelty-destroying self-disclosures. Applicants and patentees should also be careful to avoid situations in which internal and external grounds of validity are at odds, for example, where arguments or evidence required to establish support or enablement are damning for novelty or inventiveness.

The Astellas decision also reiterates that anticipation of method of treatment claims in Australia requires disclosure of the claimed therapeutic purpose but not necessarily a therapeutic effect. As established in Mylan, a reasoned hypothesis can be sufficient to destroy the novelty of method of treatment and Swiss-style claims.