Chimeric antigen receptors (CARs) often comprise a combination of known cellular domains. Consequently, experimental data is usually critical for demonstrating an inventive step. Nick Bassil and Jess Duncombe visit this issue below and highlight the types of data that can be useful for asserting an inventive step in patent applications relating to CAR technology.
Chimeric antigen receptor (CAR) technology has rapidly established itself as a valuable tool in the treatment of cancer. The results of CAR therapy for cancer patients have been dramatic in terms of providing remission of cancers where previous treatments have not been successful. The treatment is sometimes referred to as cancer immunotherapy since the CAR comprises a binding domain derived from an antibody, where the binding domain is specific for an antigen expressed on a cancer cell. CARs have been designed for expression on T cells, NK cells and Macrophages, leading to the shorthand description of CAR-T cell therapy for a CAR expressed on a T cell, etc.
In its simplest form, the CAR comprises a binding domain, a hinge domain, a transmembrane domain and an intracellular signalling domain. We take a more detailed look at CAR structure here.
The individual elements of the CAR are therefore (for the most part) elements of known cell proteins, brought together to provide a new treatment for cancer.
However, in patent law, a novel combination of known elements may not satisfy the requirements of inventive step (non-obviousness) unless there is some special technical effect. In some cases, even a combination of CAR elements with a novel antigen binding domain may not be enough to support an inventive step. For example, the EPO (unlike the USPTO) does not recognise structural non-obviousness, so even with a novel antigen binding domain applicants will typically be required to provide evidence of an unexpected technical effect.
A critical question for patent applicants in this field is often therefore whether or not the data and examples in a patent application can satisfy the test for inventive step. The data will need to show the effect of the invention, and be of sufficient relevance and quality. The examples may relate to human clinical trial data, specific treatment of individual patients in an early stage experimental therapy, non-human animal studies, or potentially in vitro cell culture studies in clinically relevant models.
In many jurisdictions, including Europe, a broad range of technical effects can be relied on to support inventive step. These include cell killing ability, target cell specificity, cytokine release (either surprisingly increased or decreased), T cell activation (either surprisingly increased or decreased), persistence of engineered T cells in vivo, suppression of tumour recurrence, resistance to re-challenge, and efficacy in specific cancer types or patient populations. As well as effects relating to therapeutic efficacy, technical effects in other areas can also indicate an inventive step, such as surprising differences in transduction efficiency compared to known CARs .
Post-filed data
If data is not available at the time of filing, or if an examiner considers the existing data in an application inadequate, in some countries it is possible to file additional data during the process of examination of the patent application.
The ability to file additional data in the case of patent applications at the European Patent Office has been the subject of much recent debate. The Enlarged Board of Appeal decision in G 2/21 sheds light on the extent to which such post-filed data can be used to support the case for inventive step in a patent application. The decision confirms that the practice can be used safely within certain limits, although consideration should still be given at the drafting stage as to whether the disclosure in an application will be suitable for introducing data during prosecution. Note that other countries may take a different approach.
Our team has considerable experience advising clients on patent matters in relation to cell therapies, including CAR-T, CAR-NK, CAR-M, engineered T cell receptors, and gamma delta T cells. If you have a question relating to these technologies, please get in touch with one of our cell therapy experts: Nick Bassil, Jess Duncombe, Abi Heath, Tom Leonard, and Amy Nick.