Opening the floodgates: Looking at the innovation and IP of immunotherapies

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With the recent FDA approvals of the first CAR-T therapies, the floodgates for cellular immunotherapies seem to be opening. In this article, Frances Salisbury (partner) and Adam Gregory (associate) — European Patent Attorneys in the Life Sciences team at Mewburn Ellis — discuss innovation and IP of these therapies in more detail.

With the FDA approving first Kymriah and now Yescarta, the floodgates for cellular immunotherapies seem to be opening, with a lot more approvals expected in the coming years. Understanding the intellectual property (IP) ramifications within this rising tide is vital, not least as the field becomes increasingly crowded and competitive.

Results of the treatment thus far are promising, with companies such as Kite Pharma and Juno Therapeutics reporting ~80% response rates to treatment of blood cancers with CAR-T. However, the methodologies involved in the preparation and administration of these treatments give rise to specific IP considerations that need to be understood.

The importance of method claims

Each patient is treated with their own bespoke medication, which is prepared from their immune cells. Cells are taken from the patient, processed, and returned to them. The patent infringement scenarios are therefore different to those for traditional pharmaceutical products, and enforcement could be more difficult with this kind of technology, as it may be necessary to demonstrate that each batch of cells falls within the scope of the granted claims.

There could, however, be real value in method claims in this area, provided the claims are crafted carefully. In particular, the treatment may involve steps occurring in multiple countries such as through a centralised processing laboratory, whereas patent infringement will be considered within only a single country. Method claims could also be especially valuable if they cover a part of the method that becomes a de facto standard required by the FDA for approval.

Both current approvals relate to blood cancers using CAR-T cells that target CD19, and we can expect the FDA to be cautious about step changes, looking more favourably on treatments that are based on methods and techniques that have been previously approved. Owning patents around these standard techniques could be extremely lucrative, thus claims relating to improvements and refinements of the processing steps should not be overlooked.

IP planning and prevention

As may be expected the clinical and patent landscapes are crowded in certain areas, and companies should consider whether they have the freedom to operate at an early stage in development. By identifying potential patent hazards early on there is the option to take preventative action. This can include making a change to the CAR construct to work around a patent right, taking steps to prevent a patent being granted, or forcing the claims to be amended in such a way that the risk is minimised. Procedures such as opposition at the European Patent Office can offer a potential infringer a cost-effective way to take action, although the impact of proceedings in one jurisdiction on proceedings in others must be considered.

While most current clinical trials focus on blood cancer, trials for solid cancers are in progress. Key obstacles to the use of CAR-T cells to treat solid tumours include lack of tumour penetration and the reduced survival of the CAR-T cells in the immunosuppressive tumour microenvironment. This may necessitate developments in how CARs are designed and/or how the CAR-T cells are administered — areas that could give rise to new patent rights.

Another limitation is the per patient treatment cost. At the moment, the average cost per treatment is ~$500,000, although the key players are working on bringing this down so that therapy is available to more patients. While current methods use autologous T cells, taken from the patient and modified to express the CAR, many companies are generating and curating ‘banks’ of immune cells which contain cells from donors with a variety of different HLA types. These cell banks could provide ‘off-the-shelf’, allogeneic, CAR-T cells. Patents directed to methods for storing and preparing such cells could prove to be very valuable, particularly if they relate to the first allogeneic T cell treatment approved by the FDA.

Further developments expected

In the coming years, we can expect to see therapies using CARs that allow for a greater control of the quality and kind of signal induced by target binding, rather than the relatively simple structures used in the first CAR-T approvals. Modifications to CAR constructs will be designed to enhance the treatment’s impact and reduce side effects such as cytokine release syndrome. Process innovations could include improvement of methods for generating and expanding CAR-T cells, and optimisation of dosage regimes. Both aspects could yield patentable subject-matter.

The recent FDA approvals are an important landmark in cellular immunotherapy. Investment and research in this area is growing, and with the numerous technical challenges there are huge opportunities for innovation. With so many patents and applications in this space, we can expect a large amount of patent litigation, and identifying whether there is the freedom to operate at an early stage will be a very important commercial consideration for parties looking to bring CAR-T therapies to market.