New EPO Guidelines for Examination: important changes for the life sciences
New EPO Guidelines that came into force on 1 March 2021 include a new subsection detailing EPO practice with respect to interpretation of terms relating to amino or nucleic acid sequences (F-IV, 4.24), as well as a new section on the examination of claims to antibodies (G-II, 5.6).
Terms relating to amino or nucleic acid sequences
Firstly, if an amino acid or nucleic acid sequence is defined by a percentage of identity, this is determined by the number of identical residues over a defined length in a given alignment. Unless an algorithm or a calculation method for determining the percentage of identity is defined in the application, the broadest interpretation will be applied using any reasonable algorithm or calculation method known at the relevant filing date.
Further, the Guidelines confirm that amino acid sequences can also be defined by a degree of similarity, expressed as a percentage of similarity. Similarity is considered broader than identity, as it allows conservative substitutions of amino acid residues having similar physicochemical properties over a defined length of a given alignment. The percentage of similarity is determinable only if a similarity-scoring matrix is defined. If no such matrix is defined, a claim referring to a sequence displaying a percentage of similarity to a recited sequence is considered to cover any sequence fulfilling the similarity requirement as determined with any reasonable similarity-scoring matrix known at the relevant filing date.
Finally, for amino acid sequences if a percentage of homology is used by the applicant as the only feature to distinguish the subject-matter of a claim from the prior art, its use is objected under Art. 84 EPC (lack of clarity) unless the determination or calculation of the percentage of homology is clearly defined in the application as filed. However, for nucleic acid sequences, homology percentage and identity percentage are usually considered to have the same meaning.
The new subsection G-II, 5.6.1 summarizes EPO practice and case law on how an antibody may be defined. In short, it is admissible to define conventional antibodies, recombinant antibody derivatives (such as antibody fragments, bispecific antibodies or antibody fusions) or new antibody formats (such as heavy-chain-only antibodies) in a claim by reference to one or more of the following features:
(a) their own structure (amino acid sequences);
(b) nucleic acid sequences encoding the antibody;
(c) reference to the target antigen;
(d) target antigen and further functional features;
(e) functional and structural features;
(f) the production process;
(g) the epitope; and
(h) the hybridoma producing the antibody.
Each type of definition is discussed in a respective paragraph giving a general idea of what should be generally acceptable and on what conditions.
Further, a separate subsection G-II, 5.6.2 provides some insight on specific requirements for new antigens to meet the inventive step criterion (art. 56 EPC). Namely, the Guidelines state that a novel, further antibody binding to a known antigen does not involve an inventive step unless a surprising technical effect is shown by the application, such as an improved affinity, an improved therapeutic activity, a reduced toxicity or immunogenicity, an unexpected species cross-reactivity, or a new type of antibody format with proven binding activity. If inventive step relies on an improved property in comparison to the enabled antibodies of the prior art, the main characteristics of the method for determining the property must also be indicated in the claim or by reference to the description.
Notably, in the case of binding affinity, the structural requirements for conventional antibodies inherently reflecting this affinity must comprise the six CDRs and the framework regions because the latter also can influence the affinity.
An inventive step can be acknowledged if the application overcomes technical difficulties in producing or manufacturing the claimed antibodies.