Patenting Antibody Related Inventions at the EPO
The antibody therapeutics sector has evolved into both an economically and commercially important sector with the EPO having recently included a dedicated section on the patenting of antibodies in the Guidelines for Examination
This new section on the patenting of antibodies considers two very important issues:
- How to correctly define antibodies, which patent protection is sought for
- The issue of inventive step, outlining the requirements for demonstrating that an antibody of interest is patentable
Antibodies can be defined in different ways including structurally, functionally or the production process.
Definition by structure (sequence) of the antibody
At least 6 complementarity determining regions (CDRs) in order to meet the EPO’s clarity requirements of Article 84 EPC.
A typical claim format would be:
‘An antibody binding to X which comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 sequences of SEQ ID numbers: 1, 2, 3, 4, 5, 6.’
An exception to this is the case where a claim to an antibody is defined by fewer than 6 CDRS. This could meet the Article 84 requirements if:
- It can be experimentally shown that 1 or more of the 6 CDRs do not interact with the target epitope
- If it concerns a specific antibody format, allowing for epitope recognition by fewer CDRs.
Definition by reference to the target antigen or epitope
Where the antibody is defined by the antigen that it binds to. Therefore providing that the antigen is new and clearly defined in the claims, an applicant can obtain broad protection. The Guidelines for Examination provide examples of antigen-defined antibody claim wording as follows:
- Binding to X
- Anti-X antibody
- Reacting with X
- Specific for antigen X
- Binding to antigen X consisting of the sequence defined by SEQ ID NO: Y
- Binding to antigen X and not binding to antigen Y
If the antigen is defined by a protein sequence; no sequence variability and no open language such as ‘an antigen comprising’ can be used in the definition. The EPO is likely to raise a novelty objection if the antigen has not been clearly defined by the full sequence. This is in view of known antibodies which can bind to the undefined region of the target antigen.
An antibody may also be defined by its epitope. i.e. The set of specific amino acids of the antigen, which are specifically recognised and bound by the antibody. The burden of proving that the antibody is different from prior antibodies that bind to the same antigen but on a different epitope resides with the applicant.
Definition by Target Antigen and further functional features
Functional features defining further properties of the antibodies can include, the binding affinity, neutralizing properties or induction of apoptosis.
Antibodies that are claimed exclusively by functional features tend to invite clarity objections and novelty objections over the prior art. Disclosing an antibody directed to the same antigen using an immunization and screening protocol that arrives at antibodies, which are considered to inherently have the claimed functional properties.
In cases that the invention relates to identifying a new antibody for a known target and defines such antibodies as using a combination of structural and functional features. This frequently used approach which is endorsed by the new guidelines, allows the applicant to claim an antibody characterized by the sequences of both variable domains or CDRs. With less than 100% sequence identity when combined with a clear functional feature.
Definition by production process or by hybridoma
Antibodies can be defined by the process of their production. I.e. by the immunisation protocol or by the specific cell lines used to produce them.
It is important for applicants to consider the timing of filing and whether they have all the information now required by the EPO. For example, some questions to consider would be:
- Are the sequences of all 6 CDR regions known?
- Are the sequences in respect of the constant regions known?
- If not all CDRs can be defined; is there information regarding the antigen to which the antibody binds or other functional attributes
- If conservative substitutions within the CDRs are to be included, are such details known
Other matters such as proof of principle data, methods of making an antibody and measurable paraments are becoming more critical in obtaining a patent for antibody-related inventions. For example, in terms of data to be included in the patent application, consider including data demonstrating target specificity and affinity as well as target binding measuring technique(s). At least one specific example should be provided of the preferred test method, including appropriate measurable parameters.
If a required level of affinity is recited in the claim, the EPO will now typically require that the claims include an indication of the technique used to determine this parameter. Preferably an explicit disclosure should be provided in the application, as filed to avoid “added matter” objections under Article 123(2) EPC. A method of producing the antibodies should be included, as a claim can only extend to what the application allows to be made.
Read our next article on Antibodies here: Inventive Step – Antibody Related Inventions