The development of cell therapies based on chimeric antigen receptors (CARs) is no different to any other field of medicine where patent claims are filed. Patent applications may therefore contain composition of matter claims, as well as claims directed to a method of treatment (or the corresponding equivalent language directed to “a composition for use in medicine”, in patent offices where method of treatment claims are not allowed), including dosage regime and patient group aspects also.
A medicine based on a CAR will usually take the form of the patients own cells, for example, the patient’s own T-cells, i.e., autologous T cells, that have been isolated and then genetically engineered to express the CAR prior to re-administration to the patient. The product is therefore a cell therapy composed of the genetically engineered cells expressing a CAR. The development of a cell therapy based on an allogeneic population of T cells would require the additional use of immunosuppressive drugs post-administration and/or potentially further rounds of genetic modification of the cells prior to administration.
In terms of a patent claim directed to a composition of matter or a method of treatment/medical use the actual formulation delivered to the patient will therefore most likely be a population of modified T cells, but NK cells and Macrophage cells can also be engineered to behave in a similar fashion.
Consequently, as a cell-based therapy questions over salt forms of the composition would not normally be relevant, but the correct adjuvants, diluents and/or buffers may well be. Other questions to consider are whether the product after the initial genetic modification is frozen, thawed and then administered to the patient, or is the product directly administered to the patient after preparation. Are there any intermediate process purification steps to consider where impurities are removed, such as additional genetic elements (vectors and/or genetic elements) from the process of genetic modification of the T cells?
Any claims to processes need to remember that the end-product may be subject to further purification or processing to make it suitable for administration to a patient. So careful drafting of process claims will be important to make sure that the “direct” product of the claim (to which patent protection is automatically extended) is actually the intended product of clinical relevance and use.
Lastly, and most importantly, in order for Patent Term Extension to be possible, the patent should be drafted in such a way that it satisfactorily protects the product authorised for medical use. In Europe, the Supplementary Protection Certificates (SPC) form of patent term extension is a separate intellectual property right that requires the product to be specifically identifiable within the patent in order for the SPC to be granted. In many cases, this will be straightforward but the test in Europe is stricter than a simple “infringement test” for whether the patent protects the product.
Patent claims directed to CARs also need to take into account the issues surrounding the patentability of claims to antibodies, since part of the CAR may be based on an antibody fragment or other specific binding molecule, e.g., a scFv antibody fragment containing the specific Complementarity Determining Regions (CDRs) that are the binding regions in the CAR which are specific for the antigen of interest. Given the strict added subject matter requirements in Europe, careful drafting is required to ensure maximum flexibility around a specific binding sequence. For example, including language that covers variation in the framework regions of the binding domain, but not the CDRs.
Case law and patent office practice in the major patent jurisdictions is consistently moving towards a stricter interpretation of the requirements for patentability for antibody or antibody-derived sequences that comprise CDRs, with little or no room for variation to preserve a broad scope of claim around the specific binding sequence. One recent development in the appeal of Ex parte Chamberlain at the US Patent & Trademark Office suggests that a means-plus-function claim might be acceptable for an antibody type claim, but time will tell if that approach is upheld by the courts in the USA. It seems hard at present to envisage the EPO allowing such an outcome.
For any advice about patent filing strategies in the field of cell based therapies, please contact Nick Bassil or your usual advisor at Kilburn & Strode LLP.