In the second of two articles relating to the patentability of antibodies, we look in greater detail at the requirements for establishing inventiveness of antibodies at the European Patent Office (EPO). We also review the type of information typically required in a patent application to evidence the inventiveness of an antibody.
Inventive Step Requirements for Antibody Inventions
As with all inventions, an antibody must, having regard for the state of the art, be non-obvious to a person skilled in the art. In addition, the EPO has set out in the Guidelines for Examination specific requirements for antibody inventions.
For instance, a novel antibody that binds to the same antigen as known antibodies will not necessarily be considered to possess an inventive step solely by virtue of being structurally different from known antibodies. Indeed, the production of alternative antibodies exclusively using techniques known in the art is considered by the EPO to be routine to a person skilled in the art. The fact the structure of an antibody obtained by such methods is not predictable fails to render a new antibody non-obvious and inventive under the EPO’s typical approach on its own.
Surprising Technical Effects and Inventiveness
As a general rule, if an antibody targets a known antigen, establishing an inventive step often relies upon demonstrating an unexpected (surprising) technical effect which is shared by substantially all antibodies falling within the scope of the claim in question. Such surprising technical effects as compared to known antibodies include, for example 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.
Structural Limitations in Antibody Claims
If the surprising technical effect relates to the binding affinity of the antibody, the claim is usually required to recite all Complementary Determining Regions (CDRs) and often also the Framework Regions (FRs) capable of influencing affinity (see EPO Board of Appeal Decision T1628/16). If the Applicant can show that variability within the framework regions does not significantly impact the affinity of the antibody, it may be possible to argue against the inclusion of the FRs in the independent claim. Similarly, if it can be shown that one or more of the six CDRs of an IgG antibody do not interact with the target epitope, then it may be possible to omit such CDRs from the claim.
In a recent decision of the EPO Boards of Appeal (T 1171/18), a claim directed towards humanised anti-biotin antibodies defined by specific heavy and light chain variable chain sequences was found to be inventive due to the presence of an unexpected technical effect.
In this case, the Examining Division (ED) had previously objected that the claims lacked an inventive step in view of prior art which disclosed a murine anti-biotin antibody from which the claimed humanised antibody had been derived. The ED concluded that the humanisation of a known antibody was obvious.
The Board rejected the ED’s decision, holding that the claimed antibodies demonstrated an unexpected technical effect when compared to the antibodies of the prior art. Namely, the affinity of the claimed humanised antibodies was only marginally reduced when compared to the known antibody. The Board reasoned that the absence of a significant affinity loss was surprising. This case provides an example of what the EPO considers to be a ‘surprising technical effect’ and also suggests that a humanised version of a known antibody may still be patentable if the humanisation process results in an unexpected effect.
Importance of Functional Data and Evidence
Proving the presence of an unexpected technical effect can often require functional data directed to this effect. The nature of such data will of course be dependent on the properties of the antibody and the surprising technical effect underlying it. Furthermore, if a functionally defined antibody relies on an improved or surprising property relative to antibodies of the prior art, the EPO may require characteristics of the method used to determine the property to be recited in the claim to fulfil the requirements of Article 84 EPC.
The importance of providing functional data directed to the unexpected technical effect of an antibody was recently illustrated by Board of Appeal Decision T 1911/17, which concerned claims to an antibody defined by its specific epitope on Brain Natriuretic Peptide (BNP).
The antibody disclosed in the closest prior art bound to the same epitope in the same manner. However, the patent proprietor argued that the binding properties of the claimed antibody were superior to that of the prior art and that the unexpected technical effects were exemplified in the patent specification.
However, the Board stated that due to a lack of evidence, it was unable to conclude that the claimed antibody did in fact demonstrate an unexpected technical effect over the prior art antibody. Thus, the claimed antibody was considered to be an obvious alternative of the prior art antibody. This Decision highlights the importance of having evidence of the unexpected technical effect to support the inventive step of the claimed antibody.
Post-Published Data and Technical Effect
A recent Enlarged Board of Appeal (EBA) Decision, G2/21, confirmed that it is possible to rely on post-published data to evidence a technical effect of a claimed antibody at the EPO or to directly compare the claimed antibody with known antibodies providing that “the skilled person, having the common general knowledge in mind, and based on the application as originally filed, would derive said effect as being encompassed by the technical teaching and embodied by the same originally disclosed invention”.
There has been little case law from the EPO Boards of Appeal since the decision in G2/21 was handed down and therefore it remains to be seen how the EPO will interpret the requirement set out by the Decision and whether post-published data will be allowed into proceedings to support inventiveness. Importantly, the EBA seemed to move away from the test of “plausibility” which has increasingly been used in proceedings at the EPO and in front of national courts in Europe.
Nevertheless, G2/21 confirms that post-published data cannot rectify a lack of technical teaching in a patent application as filed. Thus, when preparing a patent application, a balance must be struck between filing the application early with less data to support an inventive step and filing the application later with additional data that incurs the risk of encountering additional prior art.
However, it is important to ensure that an application provides sufficient information for the skilled person to obtain the claimed antibodies without undue burden. This is particularly important for antibodies defined by functional features. For instance, a recent Board of Appeal decision, T 0435/20, held that a claim to an antibody defined by its ability to bind to human IL-23p19 at an epitope comprising two specific amino acid sequences within the antigen sequence was not sufficiently disclosed by the application as filed.
Although the application disclosed a specific antibody falling within the scope of the claim (“antibody 7G10”), the application did not disclose which antigen/immunogen was used for antibody generation or the screening process that was used to select for it, and therefore no guidance regarding a suitable antigen or screening process for the generation and selection of the claimed antibodies was provided. Accordingly, even though raising and screening of antibodies entails routine techniques, the Board reasoned that the claim amounted to an invitation to perform a research program without any guarantee of success. Such a situation was considered to amount to an undue burden for the skilled person and the claim was therefore deemed insufficiently disclosed.
Conclusion
In summary, to support the inventiveness of a claim to an antibody the application must illustrate the technical effect of the claimed antibody and ideally provide detailed data to support this. If data supporting the technical effect of the claimed antibody or comparative data is not available at the time of filing, it is important that the technical effect relied upon is derivable by the person skilled in the art from the teaching of the patent application as filed. Moreover, it is important that sufficient experimental data is included in the application to allow the skilled person to obtain the claimed antibodies without undue burden. For antibodies defined by their binding to an antigen and/or specific epitope, this may require providing the antigen used for antibody generation and the screening process used for selecting the claimed antibodies.
Secerna LLP's Expertise in Antibody Patent Applications
Prosecuting antibody inventions at the EPO can be complex. The attorneys at Secerna LLP are highly experienced in drafting and prosecuting patent applications that are directed towards antibodies at the EPO.
If you would like any further information, please do not hesitate to contact us at docketing@secerna.co.uk.