The requirement that a patent specification sufficiently enables the subject matter of the claims is particularly relevant to pharmaceutical inventions and can be a hurdle for innovators even if a claimed invention is deemed novel and inventive. In the absence of any prior art, the claimed invention can fail the enablement requirement if it is not plausible at the date of filing that the invention would work across the full scope of the claims in the eyes of a person skilled in the art. As reported previously, the majority of the UK Supreme Court disagreed with the principle that plausibility is a “low, threshold test” and required that the patent specification itself provides a reasonable basis for the scope of the claims. However, a recent decision of the Patent Office in Gary B Cox v MacroGenics, Inc.  APO 13 (MacroGenics) suggests that plausibility is still a low threshold in Australia, and that the common general knowledge can be drawn upon to enable the claims.
Australian Patent Application No. 2012259162 owned by MacroGenics, Inc. relates to a protein-based therapeutic with extended serum half-life. More specifically, it is directed to a polypeptide comprising a portion of a de-immunized albumin-binding protein capable of binding to serum albumin. The de-immunized albumin-binding protein is a variant of a wild-type albumin-binding domain (ABD) of Streptococcal Protein G. The application disclosed that specific mutations of the ABDs not only extended serum half-life but also decreased immunogenicity relative to the unmodified proteins. Such protein properties are likely to maximize therapeutic efficacy without triggering a heightened immune response.
Plausibility and Undue Burden
In considering the requirement of “plausibility” under section 40(2)(a) as amended by the Raising the Bar Act 2012, the Delegate noted the absence of Federal Court authority on this provision, and cited the approach from an earlier Patent Office decision Evolva SA  APO 57 (Evolva) which stated that enablement of a claim should be determined according to a 2-step test (emphasis added):
Does the specification provide an enabling disclosure of all the things that fall within the scope of the claims, and in particular:
(a) Is it plausible that the invention can be worked across the full scope of the claim?
(b) Can the invention be performed across the full scope of the claim without undue burden?
In Evolva, the Deputy Commissioner stated that the threshold for plausibility is a low one, and may be based on the slimmest of evidence, citing Human Genome Sciences Inc v Eli Lilly & Co  UKSC 51 in which Lord Neuberger indicated that in some cases a “plausible” or “reasonably credible” claimed use, or an “educated guess”, can suffice.
The Delegate in MacroGenics also cited Warner-Lambert v Generics & Anr  UKSC 56 (Warner-Lambert), a recent UK Supreme Court judgement, regarding the plausibility aspect of enablement. In Warner-Lambert the majority of the Supreme Court found that plausibility should be derived from the disclosure of the specification read through the eyes of the skilled person in light of their common general knowledge. Although the disclosure need not definitively prove the assertion that the product works for the designated purpose, there must be something that would cause the skilled person to think that there was a reasonable prospect that the assertion would prove to be true. In contrast, the minority of the Supreme Court thought such a standard for plausibility was too high and that the patentee should not have to demonstrate within its patent a prima facie case of efficacy.
While the Delegate observed “it is clear that the Supreme Court has adopted a higher threshold with respect to plausibility…” (emphasis added) the Delegate did not see this as inconsistent with the decision in Evolva. The Delegate stated “It remains the case that, as set out in Evolva, the consideration is one of technical credibility or believability. Plausibility may be a low threshold, but it is a threshold nonetheless, and is not satisfied by mere speculation or assertion”.
With regard to “undue burden” the Delegate referenced the following statements from Evolva and Eli Lilly & Co v Human Genome Sciences, Inc.  EWHC 1903 respectively:
“My understanding of these authorities is that the emphasis in relation to undue burden has been on the nature of the work that is required by the skilled person in view of the guidance in the specification. To this end, one approach has been to ask whether the skilled person would be required to undertake a ‘research programme’ in order to perform the invention.”
“… patent specifications need not set out every detail necessary for performance, but can leave the skilled man to use his skill to perform the invention. In so doing he must seek success. He should not be required to carry out any prolonged research, enquiry or experiment. He may need to carry out the ordinary methods of trial and error, which involve no inventive step and generally are necessary in applying the particular discovery to produce a practical result. In each case, it is a question of fact, depending on the nature of the invention, as to whether the steps needed to perform the invention are ordinary steps of trial and error which a skilled man would realise would be necessary and normal to produce a practical result.”
In MacroGenics, lack of enablement was asserted in two ways. Firstly, that the conjugation of the ABD to any polypeptide was not enabled as the specification was largely directed to diabodies; and secondly that the claims were not enabled with regard to variants of the specific ABDs exemplified. With regard to the first of these, the Delegate found it plausible that fusion of a deimmunised ABD as defined in the claims to any polypeptide would extend the serum half-life of that polypeptide and that there was no undue burden on the skilled person in working the invention in this respect. As to the second issue, the Delegate found that ABD variants satisfying the functional requirements of the claim could be identified and used to extend polypeptide half-life. However, the Delegate considered that, given the large number of possible mutations to ABD, identification of variants with the desired properties would be unpredictable in light of the limited guidance provided in the specification. While such work would be routine, the Delegate was of the opinion that it would be an undue burden to work the invention across the full scope of the claims. The specification was thus found to lack enablement under section 40(2)(a).
The findings of the Delegate provides confirmation that the standard for “plausibility” is low in Australia. To satisfy this standard, the patent was not required to demonstrate a prima facie case that fusion of the claimed ABD to anypolypeptide would extend serum half-life or that the ABD variants claimed are deimmunized and could be used to extend polypeptide half-life. The Delegate stated that plausibility is a low threshold not requiring definitive proof and the Delegate appeared to notably rely on evidence of the common general knowledge rather than drawing from the disclosure in the patent specification itself. Nevertheless, due to the unpredictable nature of this technology, it was deemed an “undue burden” to perform the invention particularly because the specification provided no indication on what is and is not likely to work or guidance on how to proceed when confronted with failures.
The Delegate further noted that the present circumstances were quite different from the one contemplated in Evolva, where the claimed polypeptide was limited by sequence homology and by structure-function. MacroGenics, Inc. has been given two months from the date of the decision to amend the claims to overcome the findings of the Delegate and have filed amendments to limit the claimed ABD variant by sequence homology.
Biotechnology and pharmaceuticals are areas of technology often struck by unpredictability. While the assessment of enablement will continue to be a case-by-case approach, the Evolva and MacroGenics decisions provide some guidance on how the Australian Patent Office is likely to assess plausibility.