12 May 2021
The fundamental importance of antibodies can be seen in the pharmaceutical industry’s response to the Covid-19 pandemic. Antibodies are a vital part of the adaptive immune system, enabling the recognition of a plethora of different antigens. In healthcare, the specific binding of antibodies to a particular target protein means that they are also immensely important in diagnostics and therapeutics, and therefore innovative antibodies are an important source of intellectual property.
What are antibodies?
Antibodies, or immunoglobulins, are large protein molecules found in the body that, through communication with other parts of the adaptive immune system, specifically recognise, bind and neutralise pathogenic agents. Immunoglobulins are Y-shaped molecules typically comprising two heavy chains and two light chains, in which there are constant and variable regions. Complementarity-determining regions (CDRs) are found within the variable regions of the heavy and light chains, with six CDRs forming a paratope, or antigen-specific binding receptor.
New Guidelines for Examination at the European Patent Office (EPO) came into force on 1 March 2021. These include a section on antibodies (see GL G-IV, 5.6) which summarises the sometimes divergent case law on requirements for defining antibodies and their binding capabilities. Separately, the new Guidelines also confirm that amino acid sequences can be defined by % sequence similarity, a broader scope than that of nucleotide sequences defined by % sequence identity, as this allows for substitutions of amino acids having comparable properties (see GL F-IV, 4.24).
Antibodies might be defined by:
(a) structure (amino acid sequence)
- where binding specificity is characterised only by structure, an antibody must be defined by at least the six CDRs. These are essential technical features
(b) nucleic acid sequences that encode an antibody
(c) function with reference to a clearly defined target antigen
(d) reference to a target antigen and other functional features
- i.e., binding affinity, neutralising properties, induction of apoptosis, or internalisation, inhibition, or activation of receptors.
- It is important to remember that antibodies defined by function will lack novelty over previously described antibodies that inherently arrive at the same function.
(e) functional and structural features
- combining structural features with functional features enables more flexibility in claimed CDR and variable domain sequences
(f) production process
- i.e., immunisation protocol or specific cell line required. The antigen must be specific; variants render claims unclear
(g) antigen epitope
- for “linear epitopes” (interaction with contiguous antigen amino acids), claims must use closed wording to a specific fragment
- for “non-linear epitopes” (interaction with multiple, distinct segments from the antigen amino acids), the amino acid residues of the epitope are required, in addition to methods for identifying such epitopes and determining suitable antibodies
(h) hybridoma producing the antibody (for inventive step, see below).
Whilst patent law varies from country to country, at the EPO, novelty can be recognised for an antibody specific for a new target. An antibody comprising a new amino acid sequence would be novel over previously-described antibodies to the same target, but an inventive step must also be shown (e.g., a method of producing claimed antibodies overcoming particular technical difficulties, an improved property or surprising technical effect). An unexpected technical effect might include, for example, unexpectedly high binding affinity for a specific target, reduced toxicity or improved therapeutic activity.
It is important that the antibodies claimed in a patent application are sufficiently described in that application. This is particularly important in respect of antibodies defined by function. The scope of protection conferred by a patent is defined by the claims, but the scope of protection awarded must be justified by the support in the remaining disclosure. Antibodies capable of binding a specific target will often be described in the context of a lead candidate antibody or group of antibodies, whereas the invention of the antibodies may be claimed more broadly in terms of their function and essential features.
In order for an invention to be ‘sufficiently disclosed’, a patent must enable a person skilled in the art (e.g., a research immunologist in the case of antibody inventions) to reproduce the invention using only the teaching of the patent and what is generally known in the art at the time the patent application is filed, requiring only routine experimentation or screening.
Information provided within the application usually includes antibody binding data with the antigen target, structural data for at least one exemplary antibody with the properties claimed, details of the epitopes bound, and functional data (such as comparative data with known antibodies) showing why the antibodies claimed are inventive.
The EPO has previously concluded that whilst the production of monoclonal antibodies using the hybridoma technique may involve time-consuming work, it is considered routine and therefore not inventive (T 0431/96).
The essential features of an antibody must be sufficiently described so as to enable the skilled person to make further antibodies in accordance with the claims and without significant experimentation (T 1466/05). If the technical effect of an antibody relates to binding affinity, it is necessary to disclose all six CDR sequences and the framework regions unless data can be provided to show that the technical effect of the invention can be achieved with fewer CDRs.
It is advisable to include as much data as possible in a patent application to obtain the broadest scope of protection available. However, it is not necessary to demonstrate that every conceivable variant can be obtained (T 386/08), and supplementary data can also be filed during patent prosecution, as long as it is plausible that the technical effect is supported in the application as filed (T 1329/04).
Life Sciences & Chemistry Group
This publication is a general summary of the law. It should not replace legal advice tailored to your specific circumstances.
© Withers & Rogers LLP May 2021