Functional antibody claims in Australia – what will happen if the bar is raised?
We consider the Patent Office’s decision in Sanofi v Amgen and the future for functional antibody claims under the ‘Raising the Bar’ regime.
The multi-jurisdictional dispute regarding Amgen’s patents for anti-PCSK9 antibodies defined by certain functional characteristics has reached its first substantive decision in Australia. This article considers how the Australian Patent Office’s (APO’s) findings might have differed under the higher standards introduced under the 'Raising the Bar' (RTB) regime, in particular the new requirements of (i) support (previously fair basis) and (ii) clear and complete disclosure (previously sufficiency). The broader question arising from this analysis is: what is the future of functional antibody claims in Australia?
PCSK9 is a naturally-occurring protein in humans which was known, before the earliest priority date of Amgen’s patent applications, to bind to low-density lipoprotein (LDL) receptors (LDLR) and reduce extracellular LDLR levels. This results in higher levels of LDL (often referred to as 'bad' cholesterol) circulating in the bloodstream, which is associated with various cardiovascular disorders.
Amgen’s patent applications relate to antibodies that bind to PCSK9 in different ways so as to inhibit the binding of PCSK9 to LDLR. More specifically, they claim monoclonal antibodies that:
- bind or recognise an epitope on PCSK9 comprising particular amino acid residues, and block or reduce the binding of PCSK9 to LDLR (the 'epitope' claims);
- bind to particular amino acid residues of PCSK9, and block or reduce the binding of PCSK9 to LDLR (the “residue” claims); or
- compete with certain “reference” antibodies for binding to PCSK9, and reduce the binding of PCSK9 to LDLR (the “competition” claims).
Sanofi alleged invalidity on various grounds, including lack of fair basis and lack of sufficiency.
The APO's decision (pre-RTB)
The High Court made clear in Lockwood (No 1) that a claim will be fairly based where there is a “real and reasonably clear disclosure in the body of the specification of what is claimed, so that the alleged invention is broadly, that is in a general sense, described in the body of the specification”.
Sanofi argued that the specification at best provides a real and reasonably clear disclosure of two antibodies, referred to as 21B12 and 31H4, through disclosure of their amino acid sequences and experiments demonstrating that they block the binding of PCSK9 to LDLR. The Delegate disagreed, pointing to statements in the specification which describe the invention in broader terms. The Delegate concluded that the invention extended to antibodies that bound to the same or overlapping regions of PCSK9 as 21B12 and 31H4.
In relation to the residue claims, Sanofi also argued that the specification did not demonstrate that any particular residue of PCSK9 was actually involved in binding with 21B12 or 31H4. While the Delegate accepted this, the Delegate noted that fair basis does not require scientific proof. The Delegate considered it sufficient that binding to residues of PCSK9 could be reasonably inferred and extrapolated from the X-ray crystallography data in the specification.
The High Court made clear in Kimberly-Clark that a claim will be sufficient where the disclosure of the specification enables the skilled addressee, armed with the common general knowledge, to produce “something” within the claim “without new inventions or additions or prolonged study of matters presenting initial difficulty”. That is, for a product claim, the skilled addressee need only be able to produce a single embodiment.
The Delegate considered that the specification discloses the amino acid sequences of a number of antibodies to PCSK9, including 21B12 and 31H4, and that making these was a matter of routine.
On the residue claims, Sanofi again argued that there was no evidence that any of the disclosed antibodies actually bound to the specified residues of PCSK9, and hence no disclosure of any antibody that did so which the skilled addressee could make. In siding with Amgen, the Delegate turned this around, finding that Sanofi had not presented any evidence that 21B12 and 31H4 do not bind to at least one of the claimed residues.
The Delegate concluded that the opposition failed on these grounds, and all other grounds, and that the patent applications should proceed to grant. Sanofi has appealed to the Federal Court.
What might have happened under the RTB regime?
Would the same conclusions have been reached under the revised standards under the RTB regime? It is important to note that not only would the more stringent requirements apply but the onus of proof for Sanofi in the APO would be lowered, from “clearly” invalid to invalid on the balance of probabilities.
Under the RTB regime, the fair basis was replaced by the requirement that the claims be “supported by matter disclosed in the specification”, in line with the UK’s “Biogen insufficiency”. Two concepts underlie this requirement: “there must be a basis in the description for each claim” and “the scope of the claims must not be broader than is justified by the extent of the description, drawings and contribution to the art”.
The Delegate characterised the invention in Amgen’s patent applications (albeit in the context of the ground of manner of manufacture) as monoclonal antibodies having:
the requisite binding to interfere with the interaction between PCSK9 and LDLR and either bind to defined epitopes or residues, or compete for binding to PCSK9 with a reference antibody that comprises the heavy and light chain variable regions of the 21B12 and [31H4] antibodies exemplified in the applications.
If the APO were to characterise the technical contribution as broadly as this, Amgen’s patent applications may satisfy the support obligation. Indeed, the Delegate considered the specification to describe “a clear picture of the binding site” between PCSK9 and LDLR and demonstrate how two exemplified antibodies (21B12 and 31H4) interact in this region to block binding between PCSK9 and LDLR. These comments were, however, made in the context of “paper” disclosure required for fair basis for which, as the Delegate noted, no scientific proof is required.
If, on the other hand, the APO were to characterise the technical contribution narrowly, such as being only those antibodies specifically disclosed in the specification (e.g. by way of amino acid sequence), or even only 21B12 and 31H4, then the claims may well fall foul of the support requirement.
Clear and complete disclosure ('new' sufficiency)
Under the “RTB” regime, the test for “old” sufficiency was replaced by the requirement of a “clear enough and complete enough disclosure”. The invention must be able to be performed across the full scope of the claim without undue burden. That is, can the skilled addressee make everything within the claim?
In the US arm of this dispute, the answer to this question under US law has so far been “no”, although the US Supreme Court granted certiorari on 4 November 2022, so questions of enablement are to be revisited. Based on the evidence before the US Federal Court of Appeal, it was held that “undue experimentation” would have been required “to synthesize and screen each [antibody] candidate to determine which compounds in the claimed class exhibited the claimed functionality”. The Court found that “it is clear that the claims are far broader in functional diversity than the disclosed examples”. It was concluded that the Court had been presented only with evidence that a small subset of examples of antibodies could “predictably be generated”, taking into account the general unpredictability of the art of generating antibodies. It was also relevant that a substantial amount of time and effort would have been required to generate such antibodies.
Although this question did not need to be answered in the opposition, the Delegate did consider evidence and submissions regarding the design and production of antibodies more broadly. The Delegate accepted submissions by Amgen that the state of the art was advanced at the priority date and that it would be routine to make antibodies within the claims based on the common general knowledge and the teaching in the specification. This is in stark contrast to the US courts’ findings that the process of developing antibodies was an unpredictable exercise of trial and error.
Considerations for the future
Consideration of Sanofi v Amgen demonstrates the heightened importance of supporting data in a patent specification for the RTB requirements of support and 'new' sufficiency compared to fair basis and 'old' sufficiency.
While it is difficult to assess the findings which would have been reached under the RTB regime, including because the evidence was directed to the old standards, it is clear enough that the position under the RTB regime would likely be far less favourable to Amgen.
Although the tests for support and 'new' sufficiency are somewhat entwined and will be the subject of judicial discussion in Australia for years to come, it is not axiomatic that satisfying one test will meet the requirements of the other. For example, an invention may be able to be performed across the breadth of a claim due to the level of sophistication in the art, but if the specification does not disclose a correspondingly broad technical contribution, then the claim will fall foul of the support requirement. On the other hand, the scope of a claim may correspond to a broadly characterised technical contribution, but if the invention cannot be performed across the breadth of the invention without undue burden, then the claim will fall foul of the 'new' sufficiency requirement.
To ensure patent protection of embodiment(s) of the invention to be commercialised, patentees should at least include claims specific to the embodiment(s). Broader claims will, as always, be necessary to capture workarounds, but patentees will not be able to stretch these as far under the RTB regime without a significantly increased risk of invalidity.
A further potential consideration when drafting broad antibody claims is that, if enabled because making and testing antibodies is routine, it may be more difficult to show that such claims are inventive. Although Sanofi did not press lack of inventive step at the hearing, this may have presented a squeeze-type argument between obviousness and insufficiency under the RTB regime.
While there remain many uncertainties in this area, it is clear at least that claims to antibodies defined by functional limitations alone will be more vulnerable under the RTB regime. It will be interesting to see how the Australian approach to sufficiency develops in light of developments in the UK and Europe, including the much-anticipated decision of the Enlarged Board of Appeal of the European Patent Office regarding plausibility.
Lockwood Security Products Pty Ltd v Doric Products Pty Ltd (2004) 217 CLR 274 (Lockwood (No 1)) at .
 Kimberly-Clark Australia Pty Ltd v Arico Trading International Pty Ltd (2001) 207 CLR 1 at .
 Merck Sharp & Dohme Corporation v Wyeth LLC (No 3)  FCA 1477. For more information on this decision, see our earlier article.
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