Twenty-five years ago Tuerk and Gold reported the Selex method. Being the first European patent attorney to prosecute patents relating to aptamer/SELEX technology, Richard Clegg discusses some of the challenges at the EPO today when attempting to obtain adequate class-level protection for functionally defined molecules.
Occasionally, advances in biotechnology yield novel classes of molecule. Monoclonal antibodies represent an early example. Never patented at a class level, structurally defining monoclonal antibodies as a class would have been challenging against the backdrop of polyclonal antibody prior art available at the time—but at least antibodies have common structural characteristics that distinguish them from other substrate-binding proteins.
The Selex method
Over the years several classes of nucleic acid molecule have been identified by developing screens for functional characteristics. For example, in recent years screening for transcriptomes has generated structurally diverse pools of nucleic acids having a common functional property. Other examples are synthetic RNA and ribozymes.
In 1990, Craig Tuerk and Larry Gold reported one such method, calling it Selex (Systematic Evolution of Ligands by EXponential enrichment). It identified a new class of nucleic acid molecule that exhibits high affinity binding to a selected target molecule. In doing so they opened up a new field of research, which has led to new diagnostic and therapeutic products.
The nucleic acids identified by their method were originally referred to as nucleic acid ligands but for many years now have been referred to as aptamers. Aptamers are short nucleic acids characterised by high affinity binding to the selected target. The nucleotide sequence of an aptamer for a target is not predictable and two aptamers to the same target often have unrelated sequences.
To obtain a product (composition of matter) claim at the European Patent Office (EPO), novelty must of course be established. During novelty examination the examiner will consider whether the claim is clear enough for it to be distinguished over the known prior art. When claiming products, a molecule of a known structural type that is characterised by function alone is unlikely to be considered clear enough, particularly where the prior art contains structurally similar molecules not described, or tested, in respect of the function being used to define the claim.
The EPO’s approach
Today, antibodies can be an exception but it has taken considerable time for the EPO to reach this position and an antibody analogy can be difficult to deploy if the molecular class at hand does not have a similar distinct structural characteristic.
For example, a claim to a short nucleic acid characterised by binding to target Y, or having gene-repressing ability, will be assessed against the backdrop of a very large number of short nucleic acids in the prior art for which such functions have not been tested.
The EPO can be expected to consider that at least one such molecule in the prior art may inherently have the property at hand and, where that probability is not considered to be de minimis, can be expected to take the view that the claims are not clear enough to allow novelty to be established and/or that an undue burden is placed on a third party to determine whether a nucleic acid in their possession in fact has the property and therefore falls within the claim, ie, insufficient certainty to determine infringement.
Introducing gross structural claim limitations, eg, non-natural chemical modification, can reduce the extent of prior art to some degree but it can still be a considerable body of art and so the problem may remain.
So while pursuing class level product claims before the EPO is likely to be part of the strategy, it may be very difficult, even impossible.
Richard Clegg started working on aptamer/SELEX technology in 2003 and became the first European patent attorney to prosecute patents relating to this technology. He has since prosecuted in excess of 150 further patent applications for aptamer-related inventions.
In light of this what can be done? Find out more about strategies for obtaining class level protection of functionally defined molecules.