In our previous articles, we discussed some general considerations that are likely important for Applicants seeking to obtain international patent protection for antibody inventions. These considerations, which concerned the requirements for support and enablement, as well as the requirements for inventive step focused primarily on Australia, the US and Europe as the main jurisdictions for patent protection. The present article continues on this journey exploring patents in the immunotherapy space.
The process of patent examination with respect to antibody inventions differs significantly between Australia, Europe and the US, with Europe being the only jurisdiction of the three to have a set of guidelines for examining antibodies, based around case law of the European Patent Office (EPO) Boards of Appeal.
Antibody claims typically fall within one of several types of formats, this being claims directed towards:
- the structure (sequence) of the antibody;
- the function or target of the antibody; and
- the method of producing the antibody.
In the present article, we discuss item (1), which relates to claiming by structure. Given that this comparative guide looks at each of Australia, the US and Europe, items (2) and (3) will be discussed in separate articles.
Claiming by structure
i. Australia
For claims directed towards improvement in the properties of an antibody, the method for determining such an improvement should be disclosed. Often it is required to define the antibody according to all six complementarity-determining regions (CDRs), as well as the framework regions, in light of the “Raising the Bar” (RTB) amendments. This requirement is similar to that in Europe. However, as will be discussed under the European section, there are ways to circumvent this requirement, but only if it can be demonstrated that one or more of the CDRs do not interact with the target.
It may also be possible to pursue a broader scope of protection by claiming a percentage sequence identity to the structure of the antibody, particularly if functional features are also defined in the claim. For example in the case of Evolva SA [2017] APO 57, it was determined by the Patent Office that a polypeptide having a percentage sequence identity of at least 90%, and as defined by a functional limitation, did not result in claiming of a large number of polypeptides, and thus the test for sufficiency and enablement were found to be satisfied. The findings in this case align closely with European case law. Although Evolva discussed the concept of polypeptide and percentage sequence identities, the Australian Patent Office has along similar lines, permitted claims that relate to “at least 90% sequence identity” to the heavy and light chain variable regions, provided that there is some evidence in the specification demonstrating that such variability in sequence has no effect on the structure-function relationship.
ii. Europe
Claiming by structure is the EPO’s preferred form for claiming antibodies and involves defining the antibody according to their amino acid sequence for all six CDRs, as well as the VL and VH domains. The EPO favors this type of claiming approach since CDRs are considered to be responsible for antigen binding, whilst the framework region is considered important for influencing antibody binding affinity.
Despite the above, there have been cases whereby the EPO has permitted inclusion of fewer CDR sequences; in one case “at least three” CDR sequences, or even the absence of VH and VL sequences, if the Applicant is able to successfully demonstrate through evidence that a broad definition for an antibody, and therefore a broad scope of the claims is appropriate.
Crucially, it is important to note that by only disclosing limited structural features without describing any unexpected technical effects, would not prevent third party applicants from obtaining a ‘further’ patent based on minor modifications of a prior art antibody “structure”, if that “further” patent discloses unexpected technical (functional) effects (T 67/11 ‘Humanized antibodies / CENTRO DE INMUNOLOGIA MOLECULAR’).
Thus, it is often recommended that applicants claim a combination of structure and function, which overrides the need to claim the CDR and/or VH and VL sequences fully. In some cases, claims have been permitted whereby there is less than 100% sequence identity to the six CDRs or VH and VL regions.
iii. US
The US Patent Office (USPTO) typically favors claims that define all six CDR sequences. However, it is possible to define claims according to their sequence identify if there is sufficient disclosure of a number of supporting examples.
In one case (Ex parte Yaohuang Ke, No. 2013-009436 at 8; 10 Feb 2016), it was determined by the US Patent Trial and Appeal Board (PTAB) that a claim directed towards antibodies having a 95% sequence identity between the heavy and light chain variable regions, when compared to a reference sequence, satisfied the written description requirement, given that the specification disclosed 73 different amino acid substitutions and contained a statement that “an antibody having any of these substitutions should neutralize TNFα activity, as antibodies with all these substitutions have been shown to neutralize TNFα activity”.
Therefore, whilst claiming by structure alone offers a very narrow scope of protection, it is advisable in the US to broaden the scope of protection by incorporating some functional features into structural type claims, to avoid confining the scope of protection to only specific structural features.
Overall, it is apparent that for applicants seeking to obtain international patent protection for their antibody inventions, it would be ideal to have claims that combine structural features with some functional features. Achieving a fine balance between the two types of claim formats often offers a broader scope of protection that not only helps to justify the research and development costs associated with bringing these inventions to market, but also serves to encourage further innovations in this growing field.
