Importance of Conducting FTOs Early When Developing CAR T Cell Therapies

​Chimeric antigen receptor, or CAR, T cell therapies use the body’s own T cells to fight off cancers. The development of such cellular immunotherapies is becoming increasingly popular technology for treating cancer. Novartis’ Kymriah and Kite’s Yescarta are currently the only two FDA approved therapies on the market but many other companies are looking to launch products in this highly lucrative and therapeutically promising field.
 
Despite the promising nature of cellular therapeutics, however, CAR T cell therapeutics present some unique IP challenges that should be resolved early on in the development process in order to minimize hurdles when it comes to commercialization. Here we discuss some of these unique challenges specifically when it comes to seeking a freedom to operate, of FTO.
 
1.  Highly crowded landscape. The patent landscape for cellular immunotherapies is highly crowded with many actors already established in the space. CARs involve several different components. The current generation of CARs involve a binding domain, a transmembrane domain, a signaling domain, and at least one co-stimulatory domain. Companies already have their own proprietary CARs with modifications to any of these domains. The two FDA approved products are both directed to CD19, for instance, and many other groups are working on CD19 as well.
 
2. Multiple components. Since CAR T cell therapies involve multiple components, each of which will require its own separate FTO. As mentioned above, CARs involve a binding domain, a transmembrane domain, a signaling domain, and one or more co-stimulatory domains. To effectively launch a product without infringing a third party’s patent, each element of the CAR must have a clear FTO. Even one third party patent with claims covering any one of the CAR elements could subject the company to infringement litigation.
 
3. Method patents. Methods of manufacturing CAR T cell therapies should not be overlooked. While composition claims are often the most favored, there is significant value to patenting methods related to engineering the CAR T cells, or culturing and expanding them. Companies that develop CAR T cells may run afoul of the method claims even though the composition of the CAR T cell itself is different. Therefore, it is not only important to analyze patents directed to each of the components, but also to any methods that can be used to manufacture the cells.
 
4. Global nature. CAR T cell therapies, by their very nature, may require certain steps of the process to be carried out in different countries. For instance, the current generation of CAR T cells use autologous cells, meaning that the cells that are used and modified are those taken directly from the patient. Once they are taken from the patient, they can be transported to a lab in a different location, even a different country, for modification. The extraction, modification, and subsequent re-administration can thus happen in different jurisdictions. An FTO, therefore, should not only be limited to the country in which the therapy is going to be commercialized, but also in the countries in which individual steps of the process will be carried out.
 
Due to their complex nature, CAR T cell therapies present unique obstacles to commercialization. Companies developing products in this space need to be aware of these challenges early on in the development process so that they can take the proper actions (e.g., seek licenses, design around existing patents, challenge existing patents, etc.) to minimize their risk of commercialization.