A booming commercial interest in harnessing the human microbiome for therapeutic uses has led to a steady increase in the number of patent applications being filed in this field[1].
Microbiome-related patent applications are often directed to a single microbial strain or a composition of different microbial strains. However, defining a microbial strain is not necessarily straightforward. As discussed in our blog Replacing the bad with the good – an IP perspective on microbial consortia, the definition of the microbial strains needs to be specific enough to allow the skilled person to readily identify the claimed strain, while being broad enough to provide useful protection.
Microbes may be defined simply as being of a particular taxon (e.g., a particular genus or species). The definition might also refer to a 16S rRNA sequence, to a deposited strain (deposited with an International Depository Authority (IDA) before filing the priority application), or to a specific function of the strain.
Unfortunately, patent offices in different jurisdictions impose different requirements when examining patent applications, especially for biotech-related applications. So you might need to adapt your definition as your patent application is examined in the different jurisdictions. We therefore investigated whether the definition of microbial strains diverged in patents granted in Europe (by the EPO), the US, Japan and China.
Divergent outcomes in different jurisdictions
Using Espacenet[2] we analysed the granted claims of 15 different microbiome-related patent families (across 5 different applicants) in Europe, the US, China, and Japan. In particular, we considered whether microbial strains were defined by taxonomic name only, or whether a further definition was included (e.g., reference to a deposited strain, 16S rRNA sequence, or functional requirement).
Based on this small study, it appears that the JPO[3], closely followed by the EPO, are much more likely to grant claims which define the microbial strain by taxonomic name only (nearly 60% of granted JP patents and just over 50% of EP patents in our sample of patent families). In China, the number of granted claims with this definition of the bacterial strain was around 40%. However, interestingly, it appears that only a quarter of patents granted at the USPTO[4] had claims which simply referred to the microbe by its taxonomic name: nearly 75% of the sampled patents that were granted in the US further defined the microbial strain by reference to its function, to a 16S rRNA sequence, or a deposited strain identifier.
This suggests that the divergent requirements imposed by different patent offices do lead to different outcomes for patent applications for microbial strains. It appears that the JPO and EPO are more likely than other patent offices to grant claims that define a microbe by taxonomic name only.
So why does this matter?
Although many patents are granted with claims where a 16S rRNA sequence or a deposited strain number are used to define a microbial strain, this may lead to some potential pitfalls.
As discussed in Replacing the bad with the good – an IP perspective on microbial consortia, a single 16S rRNA gene sequence may have low phylogenetic power, particularly if only a fragment of a 16S rRNA gene is used[5]. If a microbial strain is defined in a claim by a 16S rRNA sequence, but that sequence turns out to be insufficient to distinguish the strain from other strains (e.g. if strains with different characteristics are found to have a very similar 16S rRNA gene falling within the definition used within the claim), this may create enablement issues post grant and even during examination.
As described by Johnson[6], in some cases these issues may be overcome by using modern long-read sequencing approaches, to define a strain by its entire 16S rRNA gene sequence rather than commonly targeted shorter variable regions within the 16S rRNA sequence. It has also been proposed that analysis of the full-length sequences of 16S rRNA intragenomic copy variants could provide further taxonomic resolution of bacterial communities at species and strain level, though development of this technology remains at an early stage. Whether a 16S rRNA sequence can be used to effectively define a microbial strain in a patent claim (and the necessary level of detail of the 16S rRNA sequence), will be context dependent. Caution is therefore required when considering using 16S rRNA sequences in this way.
Whilst referring to a deposited strain may represent an attractive option from an enablement perspective, the scope of such a claim remains uncertain. As discussed in MacLeod, a microbial strain could be interpreted to mean descendants of a single isolate. If the courts were to adopt this extreme interpretation during infringement proceedings, then a claim limited to a deposited strain could be found to only be infringed by a microbe that is derived from the same deposit[7]. This would mean that the granted patent would be very narrow, potentially limiting its commercial value. Of course, this does not mean that the courts would necessarily adopt such an interpretation, but it highlights a potential risk associated with what has become routinely used for defining microbial strains in patent claims.
Given that patent claims defining a microbial strain by reference to a deposited strain, or even a 16S rRNA sequence, have not been tested in infringement proceedings in the UK, it is not yet possible to definitively comment on the strength and scope of these kinds of claims. However, with these considerations in mind, it may be beneficial to include other options for defining the bacterial strain when drafting a patent application (e.g., further reference sequences or even a certain identity to full genome sequences).
Future patent filings
Interestingly, only 25% of patent families analysed were initially filed with claims already defining the microbial strain by reference to a 16S rRNA sequence, a deposited strain, or a functional definition. Of the patent families starting with claims defining the microbe by taxonomic name only, just over half ended up with at least one family member being amended to further define the microbial strain.
Therefore, if you would like to obtain claims with the broadest scope, then it may be worthwhile filing a PCT application with claims defining the microbe by its taxonomic name only (while including further definitions elsewhere in the claims and/or description).
Based on our small study, it appears that some patent offices are open to granting claims which refer to the microbial strain solely by reference to taxonomic name. However, given the apparent divergence in granted claim scope seen across the different jurisdictions, this may mean that applications in different jurisdictions may be granted with different claim scope.
Methodology
We used Espacenet to identify granted patents filed in the name of certain active companies in the Microbiome field. Only patent families with granted product and medical use claims directed to microbial strains or compositions comprising multiple microbial strains were considered. Where possible, patent families that had a granted patent in each of EP, CN, JP, and US were selected. A sample of 15 patent families with 5 different applicants (active companies) was identified. The granted patents were then sorted into two categories: (1) claims which referred to taxonomic name only or (2) claims which referred to the microbial strain by reference to a deposited strain, a 16S rRNA sequence, or by functional requirement. (Granted divisional and continuation applications were present in a small proportion of these families, but these were not considered.) The proportion of granted claims in each category for each jurisdiction was then calculated.
References
- FitzGerald & Spek. Microbiome therapeutics and patent protection. Nature Biotechnology 38: 806–810 (2020)
- Espacenet - https://worldwide.espacenet.com/
- Japanese Patent Office
- United States Patent and Trademark Office
- Janda & Abbott (2007). Journal of Clinical Microbiology Vol. 45, No. 9
- Johnson, J.S., Spakowicz, D.J., Hong, BY. et al. Evaluation of 16S rRNA gene sequencing for species and strain-level microbiome analysis. Nat Commun 10, 5029 (2019)
- MacLeod. Access Microbiology 2022; 4:000449
About the authors
This article was written by Natalie Vaughan with contributions from Eliot Ward and Edward Couchman.
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Eliot Ward
Eliot handles a diverse client portfolio spanning the life sciences sector and a growing practice in the cross-over space between physics and biology. A skilled patent prosecutor, Eliot also has wide experience of drafting patent applications on breakthrough technologies, as well as leading offensive and defensive opposition proceedings post-grant. Eliot is also experienced in handling Freedom to Operate projects and in performing due diligence, which have led to the successful completion of high value transactions and investment rounds.
Email: eliot.ward@mewburn.com
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Edward Couchman
Ed is an Associate and Patent Attorney working in the life sciences team at Mewburn Ellis. He is experienced in drafting patent applications and prosecuting them around the world, with a particular focus on the fields of immunotherapy and enzyme technology. He is also experienced in carrying out freedom-to-operate (FTO) analysis for clients looking to bring new products to market. Ed has a degree in biochemistry from the University of Oxford and a PhD in molecular microbiology from Imperial College London. His PhD research focussed on putative virulence factors in Clostridium difficile.
Email: edward.couchman@mewburn.com
