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Antibody inventions – insight provided by latest EPO Guidelines

Posted: July 9, 2021

The latest version of the EPO Guidelines contains, for the first time, a specific section on antibody inventions providing insight on the established practice of the EPO with respect to antibody inventions.  The section highlights the conditions that need to be met for the EPO to acknowledge inventive step of an antibody invention.

The EPO practice concerning antibody inventions has been developed and refined over many years, but this is the first time the EPO has attempted to formally set out their guidance.

Claiming an antibody invention

Antibody inventions can be defined in a number of ways and broadly grouped into three categories:

• Structural claims based on the sequence of the antibody;
• Functional claims based on the target of the antibody; and
• Method claims reciting the method of antibody production.

Structural definition – CDRs

Where the target of the antibody is already known, it will generally be necessary to claim the antibody at least structurally by reference to the sequence of the antibody.

Conventional antibodies have six complementarity-determining regions (CDRs), three located on the variable domain of the light chain and three located on the variable domain of the heavy chain. In conventional antibodies, all six CDRs are responsible for antigen binding.

The latest Guidelines confirm that any antibody claim defined by structure alone requires all six CDRs to be defined otherwise the claim will lack essential features and not meet the EPO’s clarity requirements. In some instances, the EPO may require both variable regions (VL and VH) to be defined if only using structural features to define an antibody.

When the CDRs are not defined by their specific amino acid sequence, they must be defined according to a recognised numbering scheme, e.g. Chothia, Kabat or IMGT to avoid sufficiency issues.  The numbering scheme used must be clearly disclosed in the application.

It is important to note that the Guidelines are for guidance only, and so in some cases, it may be possible to avoid reciting all six CDRs if one or more of the CDRs is shown not to be involved with antigen binding or if a specific antibody format allows for epitope recognition by fewer CDRs. In these instances, it can be argued that it is not essential for all six CDRs to be included in the claim.

Also, it is often possible to broaden the claim e.g. to recite a percentage sequence identity to the structure of the antibody, by also introducing a functional limitation into the claims.

This approach of pursuing a structural-functional combined claim can be used to obtain structurally broader claims, particularly when the associated functional features relates to the technical effect associated with the antibody.  Such a claim, would for example, recite “an antibody comprising at least 85% sequence identity to the six CDRs recited in SEQ ID NOs:1 and 2, wherein the antibody is capable of binding to antigen X with a binding affinity of Y”.

Functional claims based on target antigen definition

An antibody can be functionally defined by reference to a target antigen, as long as the target antigen is clearly defined in the claim.  For example, the language “an antibody, wherein the antibody is capable of binding specifically to antigen/epitope…..”

This broad claim type is generally only allowable where the target antigen is unknown.  If the target antigen is known, the EPO’s default position is that the skilled person would be able to design antibodies to known targets without inventive skill (see below inventive step section for more on this).

If a target antigen is known, an antibody can be defined by a new epitope on the target antigen.

As with defining an antibody with functional features, the burden of proof concerning novelty lies with the applicant since it may not be easy to compare an antibody that binds to a new epitope with known antibodies binding to the same antigen.

If the epitope is a “linear” epitope in that the antibody binds to a continuous amino acid sequence, the epitope needs to be defined using closed “consisting of” language to ensure the claim is novel over known antibodies.

Conversely, if the epitope is a “non-linear” or “discontinuous” epitope in that the antibody binds to multiple, distinct sections of the amino acid sequence, the specific amino acid residues that the antibody binds to need to be defined in the claim. Moreover, the method for determining this discontinuous epitope must also be indicated in the claim and the application must provide an enabling disclosure allowing the skilled person to determine whether further antibodies bind this epitope. The application must also enable the production, without undue burden, of additional antibodies binding to the same epitope.

Method of antibody production claims

An antibody may be defined by the immunisation protocol or by means of a deposited hybridoma cell line. This is a general exception to the EPO’s stance that product-by-process claims are only allowable if the product cannot be defined in other ways. Since antibodies can be defined by their structural features, it seems like there would be limited possibilities for claiming an antibody by its production process.

Regarding hybridoma cell lines, the EPO’s requirements concerning deposited biological materials will apply.

Inventive step

The latest Guidelines are clear that novel antibodies that bind to the same antigen as known antibodies do not involve an inventive step simply because they are structurally different.  This confirms that there is no principle of structural non-obviousness in Europe. Therefore, it is not enough that the sequence of an antibody could not have been predicted in advance. Likewise, simply producing a new antibody to a known target using a routine technique is also considered to not involve an inventive step.

A novel antibody binding to a known target will only be deemed inventive if the antibody exhibits a surprising technical effect, such as improved affinity, improved therapeutic activity, reduced toxicity or immunogenicity, unexpected species cross-reactivity or a new type of antibody format with proven binding activity. If the surprising technical effect of the antibody relates to an improved property when compared to antibodies of the prior art, the main characteristics of the method for determining said property must also be indicated by reference to the description, and can be included in the claim.

If the surprising technical effect relates to improved binding affinity, the structural features that permit the antibody to bind the antigen must be included in the claim. This includes the six CDRs and framework regions.

Conclusion

The latest EPO Guidelines confirm the EPO requirements for an allowable antibody claim. They also provide key information for what should be included when drafting antibody-related patent applications – particularly when relying on functional features to distinguish over known antibodies.

While these new Guidelines are specific to European practice, it should be borne in mind that any non-European priority applications relating to antibodies should also include these European-specific principles to ensure any priority claim is deemed valid in Europe.

Our attorneys in Forresters’ Life Sciences department have ample experience in drafting and prosecuting antibody patents. Therefore, should you require further information on antibody-related inventions, please contact Dr Ryan Mitchell rmitchell@forresters.boldtype.website or your usual Forresters contact.

This article is for informational purposes only and does not constitute legal advice. Please, therefore, get in touch with your usual Forresters Attorney if you need further advice.