uniQure’s AAV5 Gene Therapy Hits Support and Inventive Step Hurdles in Australia
Uniqure IP B.V is the Applicant of an Australian patent application, 2018299865, which is parent to divisional application 2024278563 and was filed on 10 July 2018, claiming priority from a European patent application with a priority date of 10 July 2017.
The application underwent several rounds of prosecution, receiving objections on the basis of lack of novelty and inventive step, lack of patentable subject matter, as well as lack of unity, clarity and support. Having undergone three rounds of examination, the Applicant requested a hearing. Following the request, a delegate of the Commissioner decided that the objections relating to lack of patentable subject matter were not sustainable. Thus, those objections were excluded from the hearing, which was heard via written submission filed on 17 January 2025. Amendments were filed alongside the written submissions.
Since the application was filed after 15 April 2013, the post raising-the-bar provisions applied.
The application related to Adeno-associated (AAV) based gene therapies in humans and to the treatment of human patients who may be harbouring antibodies directed against the AAV serotype intended for use in said treatment. Typically, those patients with neutralising antibodies against the AAV, wild-type of AAV-based vectors, will experience reduced effectiveness of treatment for AAV-based gene therapies. Instead of excluding those patients for treatment entirely, the claimed invention is inclusionary of patients with these pre-existing anti-AAV5 antibodies. In fact, claim 1 includes a pre-screening test to ensure that only those patients positive for anti-AAVS, undergo treatment and not those who have previously undergone medical treatment with an AAV5 gene therapy vector.
Since lack of clarity is not fatal when assessing validity of claims as long as they provide “a workable standard suitable to the intended use…” (Flexible Steel Lacing Company v Beltreco Ltd [2000] FCA 890 at [81]), it will not be discussed further in this case summary.
Support
For there to be a finding of support in the claims, the “extent of the patent monopoly… should correspond to the technical contribution to the art” (EXXON/Fuel Oils (T409/91) [1994] OJ EPO 653). In other words, if the technical contribution significantly advances the state of the art, then this would justify a broader scope of protection for the claims . In the present case, the Applicant argued that the specification taught a general principle that a patient previously excluded from AAV5-based gene therapy due to testing positive for anti-AAV5 antibodies may now be effectively treated with an AAV5-based gene therapy. However, the Examiner disagreed and considered that AAV5 expressing factor IX produced in insect cells, can effectively deliver factor IX to patients with pre-existing antibodies to AAV5. In other words, factor IX activity was considered essential for the claims, without which the claims could not be said to have the necessary support.
The Examiner stated that in the absence of a general theory in the specification, the technical contribution of the application could not be considered to extend further than the examples provided in the specification. This was despite the Applicant’s submissions that a skilled person would not have expected AAV5-based gene therapy to successfully work in patients with neutralising anti-AAV5 antibodies. The Applicant further argued that there is no requirement under Australian law to provide experimental data for each and every embodiment in order for claims to be supported and enabled (Evolva SA [2017] APO 57 at [67-68]), amongst other arguments such as the absence of any undue burden on the skilled person to perform the invention as claimed across its full scope of the claims.
The hearing officer did not consider the invention to relate to a new mode of therapy using AAV5 gene therapy vectors. Rather, the invention was deemed to lie in allowing previously excluded patients to receive the same treatment. Thus, the hearing officer disagreed with the Examiner’s position, instead reasoning that the requirement for support was satisfied because the invention is “not limited to a specific disease or condition, the expression system used to manufacture the AAV vector, nor is it specific to the therapeutic transgene expressed by the AAV5 gene therapy.” For that reason, the claimed invention across its whole scope was deemed supported by the specification.
Novelty
With respect to the lack of novelty objections, the Examiner acknowledged a number of prior art documents as relevant. However, the Applicant did file some claim amendments at the time of filing written submissions. The Applicant argued that a skilled person would not have even been able to hypothesise that a patient with anti-AAV5 antibodies would be able to receive effective treatment, as the test of novelty requires that there are “clear and unmistakable directions”. Thus, it would be necessary for one of the cited prior art documents to disclose that it is possible to treat a patient with anti-AAV5 antibodies, with an AAV5-based gene therapy with “an expectation of success”, which was not the case. The hearing officer considered all claims novel when assessing the proposed claim amendments.
Inventive Step
Regarding lack of inventive step, reference was made to the reformulated Cripps question, which “does not require certainty of outcome” but rather that “the skilled addressee be directly led as a matter of course to try the claimed invention in the expectation that a particular research path “might well produce” a useful result”. The hearing officer considered that pre-existing anti-AAV5 antibodies “does not necessarily lead to treatment failure” among AAV serotypes. In other words, the hearing officer did not agree that there was a common belief that any AAV gene therapy would necessarily fail in patients with such pre-existing antibodies. Reference was made by the Hearing officer to Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd [2020] FCAFC 116 at [502], to which it was commented that a skilled person does not need to be certain that AAV5 gene therapy would not be rendered ineffective by pre-existing anti-AAV5 antibodies. Rather, there only needs to be an expectation that treatment might well produce a useful result, irrespective of the pre-treatment anti-AAV5 antibody profile.
Ultimately, the hearing officer contended that whilst the patient selection process was new, the AAV5 gene therapy itself was not new and that treating anti-AAV5 positive patients does not involve an inventive step. Since there was no inventive subject matter in the specification, the hearing officer deemed it futile to provide the Applicant with a further opportunity to amend the claims. Combined with the fact that a divisional application was filed from the subject patent application, the hearing officer ordered refusal of the subject application.
Lessons Learnt: Support and Inventive Step
For satisfying the requirements of support, it is acceptable to have few experimental examples, with relatively small sample sizes, particularly if the technical contribution of the invention lies in a general principle that does not limit the scope of protection to a specific disease, condition or other therapeutic parameter.
Filing a divisional application to continue prosecution of the patent application is always a safe and highly recommended approach when it is uncertain whether the application will proceed through to acceptance and grant. This is an especially important strategy if the invention is of commercial importance, as it provides the Applicant with a second chance to pursue patent protection for their invention. Often however, the scope of protection may be narrower than initially desired, as one would have the benefit of hindsight of the types of objections and prior art documents likely to be raised during examination of the new divisional application.
