Antibody development is a mature field of technology. There are relatively few new targets, and the engineering of antibodies is becoming ever more sophisticated. As the field has evolved over the years, so has the approach taken by patent offices. Here we discuss some key considerations when filing a patent to protect a new antibody, with a particular focus on the approach taken by the European Patent Office (EPO).
1. Start from the new properties
Some patent offices (particularly the US) apply the principle of “structural non-obviousness”. Because there is no predictable relationship between the sequence of an antibody and its function, these patent offices take the view that an antibody with a distinct sequence is likely to be patentable, even if it performs the same function as an antibody which is already known.
This is not the view taken by the EPO. The EPO usually considers that if an antibody having a particular function is known, then other antibodies having the same function can be obtained as a matter of routine. While this assumption can be rebutted in particular cases, with evidence of a specific difficulty or challenge, the approach tends to mean that arguments for patentability revolve around the new functions or properties of the antibody. It is therefore important to consider at the outset what properties your antibody has that are not shared by other known antibodies – i.e., those already on the market or described in the literature.
This consideration will also help to determine the appropriate scope of protection. If an antibody binds to or does something entirely new, then it may be possible to obtain a claim that protects all antibodies having this novel binding or function, regardless of the antibody sequence. This is particularly the case if the new function has significance for how the antibody will be used, such as giving it an unexpected role in treating a disease. On the other hand, if your antibody does the same thing as one that is known but does it better, e.g., if it has a higher potency, affinity, clinical efficacy or the like, then it is likely that some kind of sequence-based definition will be required. The amount of the sequence that needs to be defined in the claim (e.g., the CDRs, the variable regions, and/or the constant regions) will depend on which parts of the structure contribute to the improvement.
2. Tell the story
In view of the considerations above, the EPO will rarely be satisfied just by knowing that a sequence is new. They want to be told the story. Moreover, the story will be more persuasive if it is told from the outset – i.e., if is written into the application at the beginning.
So, if your antibody binds to or does something new, then it is a good idea to explain in your application why this function was unexpected, or why the antibody was difficult to obtain. If the antibody has an improved function, then it is a good idea to explain why this was unpredictable or what challenges were encountered along the way.
These kinds of explanations can help both to smooth the way for the application to grant and to support an appropriate scope of claim.
3. Look for the unexpected
As the field matures, we increasingly encounter objections that certain antibody optimization techniques are routine. For example, this may include techniques such as humanization, affinity maturation and/or Fc effector function engineering. Of course, in practice these often remain challenging tasks.
In view of these objections, if the focus of the invention lies in antibody optimization, it is becoming increasingly important to explain in detail where the challenges were encountered, how these were overcome, and whether there were any unexpected results. For instance, challenges may arise from the antibody being subject to multiple constraints (such as improving affinity and neutralizing activity for one target antigen, whilst retaining these properties for another target antigen). An unexpected effect may arise from simultaneous improvement in multiple properties.
While this sort of detail may not be needed in every case, having it built in to the application can provide a persuasive response to any objections that arise, and can ultimately lead to a stronger patent.
4. Include comparative data
Comparisons to other antibodies can be used to support the story.
For example, if you are asserting that an antibody was difficult to obtain or challenging to engineer, then it can be helpful to include evidence of “failures” that you encountered along the way.
It can also be helpful to include comparisons to known antibodies, i.e., those which are already on the market or described in the literature. For instance, if an antibody is defined only by function, then an Examiner will want to be sure that this function is not inherently shared by other known antibodies, and the burden of proof is on the applicant to demonstrate this. If you are asserting an improvement over known antibodies, then the Examiner may want to see comparative data demonstrating this improvement.
Of course, it is not always possible to include comparative data in the original application. Indeed, it is often possible to provide it later, e.g., in response to in objection from the Examiner. However, where comparative data is included in the application, it can help to secure a positive reaction at an early stage. Also, if it turns out (for instance) that the supposedly novel function is in fact shared by a known antibody, then this can help to shape the way that the invention is defined and maximize the chance of being able to obtain a suitable scope of protection.
5. Check your sequences!
While the novel sequence of an antibody may not be sufficient for patentability in Europe, an accurate description of sequence is almost always necessary. Also, it is usually desirable to include a claim which is specific to a commercial product or favourite antibody, and even narrowly defined claims of this type can be highly valuable for protecting against generics competition.
It is therefore of vital importance that preferred antibodies are described accurately and completely. If there are errors in a sequence, then it is extremely unlikely that you will be able to correct these later.
6. “All 6 CDRs” – not the whole story
There is a widespread perception that antibody claims in Europe must recite all 6 CDRs or even both complete variable domains in order to be allowable. Indeed, some Examiners do try to push applicants down this route. However, that is far from the whole story, even when a purely functional definition of the antibody is not appropriate.
If it is possible to carry out mutational analysis before filing, this can allow for wild-carding of residues within CDRs or for specifying only the CDRs that are crucial for binding.
Even if such data is not available at the time of filing, allowable claims can often be obtained by combining a structural definition that permits some sequence variation and a functional limitation that reflects the inventive properties of the exemplified antibody. In this case, it will be important that the application is carefully drafted to permit these features to be combined.
7. Time your filing carefully
It is a common strategy to file patent applications at each stage of a development pathway. However, it is important to bear in mind that each patent application that is published becomes part of the background against which the inventive step of a later application is assessed. Therefore, filing a series of applications can break a development down into a series of small steps, rather than presenting the final result as a “giant leap”. The risks associated with this strategy are increasing, as Examiners consider more of the individual steps to be routine.
Of course, if there is pressure to publish results in journals or at conferences, or if a competitor is highly active, then it may not be possible to defer patent filing until a late stage of development. However, in other cases, the best chance of getting strong protection for a commercial product may come from waiting until the optimization is complete before filing. This can allow for the sequence of the commercial antibody to gain strong protection, while at the same time allowing for a good breadth of claim.
As always, we recommend seeking early advice from a patent attorney, in order to determine the best strategy for your particular circumstances.
About the authors
Chris does life sciences patent work and is renowned for his expertise in the pharmaceutical sector. He handled the prosecution and opposition defence for most of the European patent portfolio and provided litigation support for two of the top-ten bestselling biopharmaceuticals. Chris also has an interest in the biotechnology, food & beverage, Medtech and oil & gas sectors.
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