Gene therapies involve treating patients by manipulating their genetic makeup. Such therapies may involve introducing corrected versions of defective genes, shutting-down the expression of disease-causing genes, or modifying existing genes or gene products in the body.
Many countries prohibit the patenting of genetic material per se. Some patent offices may take the view that it is obvious to repair or replace a defective gene known to cause a disease, or that it is obvious to design transgenes that target a known sequence. So, how can such inventions be protected? Spoiler: experimental data is key!
I have generated a new transgene – can I protect its sequence?
Potentially, yes! Although the wild type sequences of most genes are known, transgenes destined for use in the clinic may undergo alterations or modifications that could result in novel, patentable sequences. The bigger hurdle is whether such transgenes are non-obvious.
Codon-optimisation to improve expression from particular cells is a common modification. So common in fact, that we’re starting to see some patent examiners, e.g. in Europe, objecting that it is an obvious and routine step in transgene development. The generation of antisense molecules (siRNA, miRNA) against known gene targets can also be considered routine by the patent offices.
Other modifications like minigene sequences, where non-essential domains of transgenes are removed, and split transgenes, designed to fit into multiple vectors, may encounter similar challenges.
The chance of successful patent protection can be improved dramatically if the patent applications are drafted to tell an ‘invention story’. Experimental data is key! In particular, the inclusion of comparative data showing unexpected, unpredictable or surprising effects for the lead sequences will be extremely helpful. Including the wild-type gene sequences and non-working variants in the experimental data will often strengthen the story.
Examples of useful comparative results that can support non-obviousness:
- Several codon-optimised sequences are tested in the target cells, and some are found to be expressed better than others.
- A number of siRNAs are tested against a target sequence and only a subset of sequences is found to provide effective knockdown of expression.
- Different minigenes are generated containing various domains. Some minigenes are found to have unexpectedly good expression and/or efficacy that could not have been predicted from their domain selection.
What if I have discovered a new gene-disease relationship?
Fantastic! There is an opportunity here to pursue broader claims that are focused on the mechanism of treatment itself, as well as any specific transgene sequences.
Think about claims to methods of treatment by up- or down-regulating the key gene(s) causing the disease, without limiting to any particular gene therapy modality. Again, experimental data is fundamental. The patent application must demonstrate to the patent offices that the target gene(s) are directly involved in the underlying disease mechanism, i.e. that modulating said gene really will have a treatment effect. In vivo data is not essential, but it will probably strengthen the invention story.
Careful drafting may be required to meet global requirements for method of treatment/medical use claims, and to avoid falling foul of various patent office requirements for support and enablement for broad treatment claims.
Specific transgene sequences that target the key genes could be protected in separate patent applications to allow more time for development. Staggering the filing of these applications also provides an opportunity to extend patent term for the clinical products.
What if I can deliver my transgene in a superior way?
Your transgene might be very similar to others that are already known, and the disease mechanism may be well documented. However, delivering more functional transgene to the desired site of treatment or improving the stability of the transgene can be an invention in itself.
A combination of the transgene and a particular viral vector might lead to improved expression in target cells and/or superior delivery to target tissues. A particular non-viral delivery method may result in more of the transgene entering the desired cells, for example by improving stability of the transgene during delivery and/or at the target tissue. Again, data is critical to support such inventions, ideally providing a comparison to less effective delivery methods.
Even combinations of known vector components (promoters, enhancers, stuffer sequences, etc.) alongside the transgene may be patentable if the experimental data shows that some combinations work surprisingly better than others.
Of course, entirely new viral and non-viral delivery methods can also be patentable in their own right, and may have huge commercial value if they become leading technologies in the field.
Should I file an application if the components of my gene therapy are not yet finalised?
Ideally, one would wait until the lead products are more fully realised before filing. However, we know that this is not always possible!
In such cases, it is important to build in as much flexibility as possible into the patent application to allow various combinations of components to be pursued later if necessary. This is particularly important for places like Europe, Japan and China, where a very strict approach is taken to combining different embodiments after filing without explicit basis in the application.
Careful drafting and fall-back positions can make it easier to mix and match components later on. It is also a good idea to include language describing sub-groups of transgene sequences, e.g. that share structural and/or functional features. This can help to keep some breadth in the claims and may avoid having to limit to just one or two sequences during examination.
Go forth and patent!
As gene therapies develop, so must the strategies for protecting the basic building blocks of these technologies. There are many opportunities to obtain patent protection and careful drafting of patent applications by experts in these technologies will maximise the chances of success.
And, for one final time… the better the experimental data, the better the prospects of the patent application.
Our Advanced Therapies team has a wealth of experience in this area. Get in touch and find out how we can help you.
This blog was co-authored by Laura Carney and Anna Mudge.
Laura Carney
Laura is a Senior Associate and Patent Attorney at Mewburn Ellis. Laura handles a wide range of patent work in the life sciences sector, from pre-drafting advice to drafting and prosecution of worldwide patent portfolios. Laura also has experience with European oppositions.
Email: laura.carney@mewburn.com
