The disclosure requirements for patent specifications were raised in Australia following the commencement of the Intellectual Property Laws Amendments (Raising the Bar) Act 2012. Under the new Act, a patent specification must provide sufficient information to enable a person skilled in the art to perform the invention across the full scope of the claims without undue burden or the need for further invention. The new disclosure requirements have received little attention from Australian courts, but two Patent Office decisions provide some guidance as to the level of disclosure required to support claims directed to polypeptides.
Evolva SA [2017] APO 57
Evolva SA [2017] APO 57 ('Evolva') concerned an application describing compositions and methods for glycosylating mogrol using uridine-5'-diphospho-dependent glycosyltransferases (UGTs). While the specification described five UGTs that glycosylate mogrol, the claims went further, encompassing the use of polypeptides having 90% sequence identity to any one of the five UGTs. The examiner rejected the claims, alleging that an undue burden would be placed upon a skilled person in order to produce every polypeptide encompassed by the claim and then determine which ones exhibited the desired activity. Seeking to resolve the matter, the applicant requested a hearing with the Patent Office.
The decision
In the absence of Australian authority, the Delegate in Evolva drew upon European and United Kingdom authorities, and adopted the following two-step inquiry into whether the specification provided an enabling disclosure:
- Is it plausible that the invention can be worked across the full scope of the claim?
- Can the invention be performed across the full scope of the claim without undue burden? (at [45]).
The answer to each question will depend on the specific technology at issue, the skills and background knowledge possessed by the notional person skilled in the art and the teachings provided by the specification. On the issue of the person skilled in the art, the Delegate did not agree with the examiner's assessment of the relevant person being "a single synthetic chemist, perhaps a PhD candidate". Rather, the Delegate described the hypothetical skilled person as a team, including biotechnologists and synthetic chemists (at [54]). Against this background, the Delegate then considered the first question in the two-step inquiry, namely the question of plausibility. Based on what was known about the structure and function of UGTs, the Delegate concluded that the skilled person would find it plausible that variants to a level of identity of 90% could be identified and would be useful in the claimed methods (at [62]). On the question of undue burden, the Delegate found that the specification sufficiently described how UGT variants may be generated and tested. The Delegate acknowledged that such tests could involve time-consuming experimentation, but they did not, it was found, amount to an undue burden in the relevant field of technology (at [68]).
Gary B Cox v MacroGenetics, Inc. [2019] APO 13
In 2019, the Patent Office again considered the sufficiency of claims directed to a polypeptide. This time the application concerned therapeutic proteins having an extended serum half-life. The proteins comprised an albumin-binding domain (ABD) portion that could bind to serum albumin – the most abundant protein in human blood plasma – and thereby extend the half-life of the entire protein.
Claim 1 of the application defined a "polypeptide" comprising a variant ABD capable of binding to serum albumin. The variant ABD was defined as having an amino acid sequence that differs from the wild-type ABD in "comprising" one of two combinations of amino acid substitutions, referred to in the specification as AAA and DSA. The claim also included two important functional limitations, namely that the ABD is deimmunized and that it is albumin-binding.
The decision
In determining whether the claims were sufficiently enabled, the Delegate adopted the two-step inquiry that was laid out in Evolva. In considering the first step of the inquiry, the Delegate observed that "plausibility is a technical consideration and assertions must be based on a reasonably credible technical or scientific basis derivable from the specification as understood by the skilled person" (at [61]). With regard to the second step of the inquiry, the Delegate observed that what constitutes an undue burden will necessarily depend upon the nature of the technology, the level of predictability in the art and the level of guidance in the specification (at [66]).
Turning then to the claims, the first element at issue was the term "polypeptide", which encompassed more than the fusion partners exemplified in the specification. Although the specification only exemplified a limited number of diabody fusion partners, the Delegate was satisfied that a skilled person would find it plausible that a deimmunized ABD could be used to extend the serum half-life of any polypeptide. In the context of the claims, the Delegate described the polypeptide to which the ABD is conjugated as a "principle of general application" (at [83]).
The Delegate then turned to the variant ABD, which was defined in the claims as "comprising" one of two combinations of amino acid substitutions, ie, the AAA and DSA mutations. The term "comprising" has been given both an open and a closed meaning by Australian courts. In the present case, the term was construed inclusively such that the variant ABD may have any number of mutations, provided that it has either the AAA or DSA mutations. In considering the nature of the work that would be required for a skilled person to perform the claimed invention, the Delegate acknowledged that the level of skill of such a person would be high, and that the specification provided examples of combinations of ABD mutations and their effect on albumin binding (at [95]). However, it was not apparent to the Delegate that a skilled person would appreciate what mutations could be combined with the AAA or DSA mutations whilst achieving the functional limitations of the claims. To the contrary, the evidence suggested that combinations of mutations would have an unpredictable effect on albumin binding (at [97]) and could even introduce immunogenic regions (at [99]). The Delegate found that the work required to identify variants having the desired properties, particularly albumin-binding ability, while systematic and iterative, is unpredictable, with limited guidance provided by the specification. The work required to perform the invention across the full scope of the claims was found to constitute an undue burden, being "in the nature of a research project" (at [107]). As such, the Delegate found that the specification did not provide a clear and complete enough disclosure of the claimed invention insofar as it relates to variants of ABDs with unlimited further substitutions.
Conclusions
In considering whether a claim to a polypeptide is sufficiently enabled, the Patent Office will ask: i) whether it is plausible that the invention could be worked across the full scope of the claim; and ii) whether the invention can be performed across the full scope of the claim without undue burden. The answer to both questions will depend on several factors including:
- the specific sequence being claimed;
- the disclosure provided by the specification;
- the identity of the notional person skilled in the art; and
- the polypeptide's function.
The specific sequence being claimed
Certain polypeptides, and indeed certain regions within a polypeptide, will be more tolerant to amino acid changes than others whilst maintaining the functionality of the polypeptide. In the case of antibodies, for example, one might expect that an amino acid change within a complementarity determining region (CDR) would be more likely to affect binding activity compared with an amino acid change within a framework region. (Although amino acid changes within the framework region can, of course, impair the folding within, or the pairing between, the variable domains.) Accordingly, the Patent Office may allow a greater degree of sequence variability in a claim that defines the variable region of an antibody as compared to a claim that defines the CDRs. For claims which define an antibody solely by reference to the sequence of its heavy and light chain variable regions, Australian examiners have allowed up to 90% sequence identity.
The disclosure provided by the specification
A claim that encompasses a broad range of polypeptides is more likely to be supported in circumstances where the specification discloses a technical rationale - ideally, but not necessarily, in the form of experimental data - that makes the claimed invention plausible to a person skilled in the art and provides the person with guidance as to how the invention can be worked across the full scope of the claim.
The person skilled in the art
The notional person skilled in the art may carry out ordinary methods of trial and error and may use their common general knowledge to supplement the information contained in the specification. A highly qualified person, or a team of highly qualified people, will have a wide breadth of skills and knowledge at their disposal when it comes to assessing the plausibility of, and to performing, the invention as claimed.
The polypeptide's function
Including functional limitations in a claim may render it insufficiently enabled if substantial work would be required to test for the presence or absence of those functional limitations, particularly if the technology is unpredictable.
