Cancer immunotherapy is an extremely promising area and it has been a game changer since the approval of the drug Yervoy© (ipilimumab) in 2011. Currently, 13 drugs have already been approved for immunotherapy for 16 different types of tumours.
Technological and business developments have grown hand in hand with patent protection. More than 450 patent applications were published in 2018 under the Patent Cooperation Treaty (PCT), against around 60 in 2014. Two technologies have undergone major development: ICIs (immune checkpoint inhibitors) and CAR-T cells (chimeric antigen receptor T cells).
Immune checkpoints make it possible to regulate the immune response, thus preventing attacks on the body’s own cells. Unfortunately, this strategy is also used by tumours, which are able to adapt and multiply without being detected by the radar of the immune system. ICIs, the discovery of which was awarded a Nobel Prize in 2018, are drugs that are able to block this escape strategy.
More recently, a new class of therapies has emerged which use cells that are extracted from the patient’s own body and are genetically modified to recognise certain tumour cells, becoming super competent in combating the tumour. One of the most promising techniques uses CAR-T cells.
The class of ICIs essentially includes antibodies and CAR-T technology involves the use of genetically modified cells. Both represent a challenge for IP strategy, as the patentability of genes and methods of treatment is subject to limitations in various jurisdictions, particularly in Europe. Due care in the drafting of the patent, as well as careful planning of the underlying experimental trials, can help ensure the adequate protection of these patents.
ICIs are growing rapidly and have enormous potential to become blockbuster drugs in the near future. It is not surprising that the major players have already marked out their position, contributing to the intricate web of patents. However, patents for antibodies, which are defined by their genetic structure and/or by their functional characteristics, represent a fragile balance between legal uncertainty and the commercial exclusivity obtained that must be strategically evaluated.
CAR-T technology raises questions that are no less challenging. Instead of a mass-produced drug, the use of a patient’s own cells obscures the borderline between medicine and method of treatment. However, there are aspects of the process and product that are potentially patentable, namely genetically modified cells or DNA vectors used in the modification process.
In another approach, anti-tumour vaccines are showing themselves to be a promising form of immunotherapy that can help teach the immune system what tumour cells are like, making them easier to recognise and eliminate. There are two types of anti-cancer vaccines, preventive and therapeutic vaccines. Viral infections are responsible for the development of various types of cancer, such as cervical, head and neck cancer, caused by the human papillomavirus (HPV), and liver cancer, caused by the hepatitis B virus (HBV), and preventive vaccines play an important role in reducing the risk.
Therapeutic vaccines, in turn, contain tumour cells or parts of tumour cells, or pure antigens, and they increase the immune response against cancer cells that are already present in the body. However, since each tumour is unique and has its own distinctive antigens, particularly sophisticated approaches are needed. To date, only two therapeutic vaccines have been approved: Sipuleucel-T (Provenge®) for the treatment of prostate cancer, composed of the patient’s own stimulated dendritic cells, and Bacillus Calmette-Guérin (BCG), approved for the treatment of early-stage bladder cancer, which uses weakened bacteria to stimulate the immune system. Phase I and II trials are underway for the treatment of melanoma and kidney cancer. A phase I trial with mRNA encapsulated in liposomes for patients with advanced melanoma is also being conducted.
mRNA vaccines are emerging as a promising alternative to the traditional vaccine platforms, both for infectious diseases and for oncological application, as they can be manufactured quickly and adapted to a wide range of conditions. Various mRNA vaccines have been perfected and validated in immunogenicity and efficacy studies and, as a result, in the last 10 years, approximately 70% of patent families relating to mRNA vaccines have been registered by industry, with Moderna, CureVac, BioNTech and GSK holding almost half of the patent applications in this area.
Patenting in the area of mRNA vaccines reveals a growing number of applications intended to protect methods for improving the efficacy of mRNA transport, namely compositions of lipid nanoparticles (LNPs), as well as pharmacological modifications to reduce the instability of mRNA and innate immunogenicity. Exponential growth is expected as a result of the increased investment in mRNA vaccine platforms, but also due to the results of the accelerated clinical trials that are currently being conducted. The expected positive results in these trials will not only be a tremendous advance in the fight against cancer, but will also provide a powerful and versatile therapeutic tool for outbreaks of infectious diseases, like the current challenge created by SARS-CoV-2. For example, four of the vaccines that have already been approved or are awaiting approval for use against COVID-19 are RNA vaccines: mRNA-1273 (Moderna), BNT-162 (BioNTech), CVnCoV (CureVac) and LNP-nCoVsaRNA (Imperial College London).
In an increasingly overcrowded technological landscape, patents with broad protection will be more difficult to obtain and innovators will have to adopt cautious strategies. Patent monitoring and licensing will be essential for the development of new products, although litigation will be inevitable in view of the number of players, business potential and risks involved. CRISPR-Cas9 gene engineering is one of the technologies underlying the advancement of CAR-T cells and it provides a real-life example of fundamental patents in dispute in the United States and in Europe. Some patent holders have proposed the establishment of patent pools, similar to those established in the mobile telecommunications sector, where holders contribute with relevant patents to be licensed as a package, with the advantage of providing a substantial flow of income to the holders and an incentive for the development of patents of better quality.
