MICROBIOME
Microbial consortia: establishing a strong IP position in Europe
Protecting new and inventive innovations in this increasingly crowded area is essential, explains Ine Vanderleyden of Mewburn Ellis.
Our body hosts trillions of microorganisms that live symbiotically on and within the human body. This ‘microbiome’ is essential to our health and microbial imbalance or dysbiosis increases the susceptibility to many diseases, including inflammatory bowel disease (IBD), liver disease, atherosclerosis, and other severe pathologies. Given its central role in health and disease, the microbiome has become a prominent therapeutic target.
Microbial consortia
In two early proof-of-concept studies, researchers were able to restore microbiome balance in patients with IBD and Clostridum Difficile infection using Fecal Microbiota Transplantation (FMT), essentially replacing the ‘bad’ bacteria with ‘good’ ones from healthy donors. These initial studies provided an impetus for the development of therapeutic compositions that contain microorganisms, with many targeting the gut.
One category of microbiome-targeting therapies uses groups of bacteria that cooperate within a larger community, a so-called microbial consortium. Microbial consortia are believed to result in a more durable engraftment because of the establishment of a new ‘micro‘ ecosystem, and, consequently, improved biological functionality compared with using single bacterial strains.
Following isolation from biological samples, typically stool or saliva, groups of bacterial strains are propagated in clonal cell banks and consortia are selected based on a desired biological function, such as metabolite production or outcompeting pathobionts (disease-causing or harmful microorganisms).
For example, a consortium of bacteria designed to complement missing or underrepresented functions in the imbalanced microbiome of IBD patients was found to prevent and treat chronic immune-mediated colitis in humanised mouse models by decreasing pathobionts while expanding resident protective bacteria.
IP considerations for microbial consortia at the EPO
The IP strategy for therapeutics in the microbiome field differs from the more traditional drugs because microbes, the active ingredient, present in a consortium may be well known and thus not novel, or naturally occurring and considered a discovery, which is excluded from patentability in Europe.
”Several groups are now working on engineered or synthetic microbial consortia designed to carry out specific biological functions.”
Ine Vanderleyden
It is nevertheless possible to obtain IP protection for these consortia provided the application or therapeutic use is new and inventive. For example, a particular set of known bacteria acting synergistically, or capable of performing a desired function, may be patentable.
Notably, several groups are now working on engineered or synthetic microbial consortia designed to carry out specific biological functions. These engineered consortia are of course not naturally occurring, and it may be possible to obtain protection for the consortium as such as well as its use.
Types of claims
Typically, product (“composition of matter”) claims to a composition comprising the consortium or to the engineered consortium per se are commercially most useful and enforceable. Secondly, while the European Patent Office (EPO) does not allow claims directed to methods for treatment, purpose-related product claims directed to particular substances or compositions for use in methods for treatment are allowed.
Critically, these so-called medical use claims require suitable evidence in the application for the claimed therapeutic effect. This does not have to be in vivo data and in vitro assays may suffice as long as they make the therapeutic effect credible.
While drafting it is also worth keeping in mind the commercial end-product and include claims to, for example, a food product or vaccine comprising the composition or consortia as appropriate. Other claims to consider, ensuring the broadest protection possible, are methods of identifying and manufacturing (synthetic) consortia and formulation claims.
Common pitfalls: support and sufficient disclosure
As explained above, microbial consortia are typically selected for and defined by their desired function. However, functionally defining consortia in a patent application does not necessarily allow the skilled person to obtain the claimed consortium, and this often leads to objections of lack of sufficient disclosure at the EPO.
Another common pitfall relates to an alleged lack of support in the description of the application due to the exemplification of only a few subsets of bacteria providing a claimed effect. It is important to mitigate against objections of sufficient disclosure and support as much as possible at the drafting and filing stage because these can be fatal to a patent application. A fundamentally insufficient disclosure cannot be ‘fixed’ after filing.
Including 16S rRNA sequences in the application is one way of mitigating against objections of lack of support or sufficient disclosure. However, because 16S rRNA gene sequences have low phylogenetic power at the species level and poor discriminatory power for some genera, they do not necessarily allow a skilled person to obtain the claimed consortium without undue burden.
It is therefore advisable to include structural characteristics of the bacteria (eg, accession numbers), and/or technical features of the isolation method necessary for obtaining the microbial consortium with the desired properties in the application as filed. This is especially important in cases relying only on a sequence listing or instances where known bacterial strains are used.
Including data supporting the effect of bacterial strains on the molecular mechanism underlying a therapeutic effect may also allow for medical use claims with a broader scope. If these data are not readily available, it will still be possible to obtain narrower claims directed to the use of the bacteria in a specific condition, provided there is data showing that the bacteria successfully treat the condition.
Depositing the consortium with an International Depository Authority (IDA) before filing the priority application provides the strongest position to avoid any alleged insufficient disclosure or lack of support. If the actual component of the microbial consortium that achieves the desired effect is unknown, a deposit is often the only option for meeting the sufficiency and support requirements.
Understandably, applicants are reluctant to deposit their consortia due to concerns over third parties obtaining and exploiting physical samples of the invention. At the EPO, the expert solution provision mitigates this risk by only allowing the release of the biological sample to an independent expert nominated by the requester, not the requester itself, and typically only after the publication of the patent application.
The deposited material may only be used for experimental purposes and may not be transferred to third parties. Typically, it provides the opportunity for third parties to confirm experimentally that the deposit is what an applicant says it is in an application.
It is worth pointing out that even with an expert solution request in place to limit access to the biological sample, samples are still released to the public when the patent is granted, or 20 years after filing if the patent application is refused or withdrawn. This means that even if the patent application is abandoned after publication, the biological sample will eventually become available to the public.
”A reasonable conclusion to draw from these cases is that the protection may depend on whether the product supplied qualifies as a ‘patented invention’.”
Navigating an increasingly crowded space
The microbiome space is becoming increasingly crowded, and this is reflected in a steady rise in the number of patent filings in this field. Establishing a strong IP position in the early stages of development of these therapies is therefore essential.
Of course, the increasing volume of prior art publications in this space will impact the typical claim scope that is available. Useful fall-back positions must be included in your patent application to overcome potential novelty and inventive step objections. As the field matures, the main challenge will likely become successfully demonstrating inventive step.
The skilled person will gradually be considered more aware of “routine” techniques in this area of technology, making it necessary to clearly describe surprising or unexpected effects of the invention in detail in the specification.
Critically, the EPO has an infamously strict approach to added matter so it will be important to ensure that there is direct and unambiguous basis for any fall-back positions at the drafting stage.
A number of patents relating to microbial consortia have been granted by the EPO, and, for now at least, it seems that innovators are able to obtain broad claims to many aspects of the technology. However, the real test of how well these broad claims stand up to challenge takes place at the opposition stage at the EPO.
The EPO’s opposition division appears to be taking a favourable stance on microbial consortia, illustrated by opposition proceedings against EP 2,575,835. The patent in this case related to a composition that induces proliferation and accumulation of regulatory T cells (Tregs), comprising, as active ingredient, spore-forming bacteria belonging to the genus Clostridium, for use in the treatment of various diseases, including infectious diseases.
The patent was opposed by no less than six other parties, with the main arguments centring around sufficiency of disclosure, novelty, and inventive step. The opposition division dismissed the objections and decided that the patent was valid because the invention relied on the technical effect of Treg induction identifying a new clinical situation and a new sub-group of patients, in spite of some overlap between the composition and treated diseases with those of the prior art.
While this outcome appears to be promising for patent proprietors, the decision is under appeal and it remains to be seen whether the EPO maintains its generous view.
Ine Vanderleyden is a patent technical assistant in the life sciences practice at Mewburn Ellis. She can be contacted at: ine.vanderleyden@mewburn.com
Images, from top: Shutterstock / Cryptographer, Siberian Art
