In a new age of personalised cancer therapy, is patent law in Europe still fit for purpose?

In the last week it has been announced that the NHS has struck a deal with Novartis to offer their ground-breaking new CAR-T therapy, Kymriah®, to paediatric patients with B cell acute lymphoblastic leukaemia. This is a significant development and means that some patients will now have access to this new type of advanced (and costly) personalised medicine on the NHS to treat their cancer in instances where all other treatments have failed. This deal highlights the changing approach to cancer treatment that has been rapidly developing over the past several years and the need for NHS patients to have access to more targeted and advanced therapies.

Cancer treatments generally rely upon surgery, radiotherapy and chemotherapy. While many patients benefit from these therapies, there remain a large number of patients whose cancers don’t respond. Cancer research over the last few decades has been focussed on methods to harness the patient’s own immune system to target and destroy cancer cells, particularly in blood cancer treatment where conventional methods are less effective or not possible. There are a number of approved cancer medicines that comprise these immunotherapies. Most are so-called monoclonal antibody therapies, which utilise very specific binding molecules that seek out and attach to cancers in a bid to stimulate the patient’s immune system to take over. These can be effective when the patient has a cancer that matches the available medicine, for example breast cancer patients whose cancer is HER2+ can benefit from treatment with Genentech’s Herceptin®, which is available on the NHS. However, there are many patients whose cancers don’t match the available medicines or who may benefit from an alternative, more personalised, approach. Personalised therapies are costly because each batch of medicine is prepared and tailored to a specific patient so cannot typically be “scaled up” in manufacture for use in multiple patients in the same way as antibodies and conventional small molecule medicines.

Personalised cancer therapies are often referred to as adoptive cell transfer as certain cells from the patient’s own immune system are extracted, modified and re-infused into the patent to target the cancer. Some such therapies work as “immunostimulants” by modifying antigen presenting cells, which help the patient’s immune system to find the cancer, for example therapeutic vaccine Provenge® for advanced prostate cancer. Others in development include LIfT BioSciences’ granulocyte therapy, which harnesses the patient’s less specific innate immune cells to attack cancers. Other therapies, such as CAR-T, modify the patient’s T-cells to directly seek out the cancer cells and are essentially a dramatic improvement of conventional antibody therapies.

2017 saw the US FDA approval of the first two CAR-T therapies; Novartis’ Kymriah® and Kite/Gilead’s Yescarta®. The European Medicines Agency approved Yescarta® in August 2018 and has recommended Kymriah® for approval. These therapies work by taking a patient’s own T-cells and engineering them to produce a specially designed receptor (much like an antibody) on their surface, which recognises a specific marker found on the surface of tumour cells. After the T-cells have been engineered they are grown in a laboratory before being reintroduced to the patient. Once inside the patient the patient’s own targeted T-cells recognise the tumour cells and direct the host immune system to attack the cancer. They act as a “living drug” that more effectively and dynamically stimulates the patient’s immune cells over a longer duration than antibodies on their own.

These bespoke therapies are a major advance as they enhance a patient’s own immune system and they will likely avoid many of the side effects associated with other cancer therapies. Further, advances mean that the receptor could potentially be tailored to the patient’s own cancer meaning potentially any patient could benefit.

As with any medicine, the high cost and the length of time it takes to get these therapies through discovery and clinical trials to market means that an effective patenting strategy is essential to secure investment and maintain market share. However, the European patent system does not lend itself easily to the protection of these personalised cell-based therapies, perhaps unlike the US patent system.

In Europe, unlike in the USA, it is not permissible to patent “methods of treatment”. Instead, the practice is to focus patent protection on the medicines themselves, and, in certain instances, new uses of those medicines (i.e. drug re-purposing). These strategies are suited to protecting medicines that can be clearly defined and which are manufactured to a particular specification, packaged, distributed and sold in a particular territory. These patents can be used to prevent unauthorised manufacture, distribution and sale of such medicines by third parties. However, as individual CAR-T therapies are personalised to the patient it may be more difficult under the current European patent system to define and claim the actual medicine administered to the patient in a way that will enable patent protection of medicines prepared from different patients. Also, restrictions on patenting parts of the human or animal body come into play. Further, the manufacture of CAR-T therapies involves a number of steps, carried out by medical practitioners and laboratories alike, potentially in different locations (possibly across borders) by different organisations. In the USA, while methods of treatment are patentable, medical practitioners are protected from patent infringement by other laws, whereas in Europe the same result is achieved by actually preventing the patenting of methods carried out by medical practitioners. Further, in many territories, if a patented process is only partly carried out by one organisation (and the rest by another or not at all), then it may be difficult to prove that they are infringing the patent.

In the light of these matters it may seem that crafting a patent to cover CAR-T therapies that will provide effective enforceable protection from would-be infringers would be challenging in Europe. Arguably, a system more akin to the US approach would be more effective for the protection of CAR-T but we must of course work within the confines of the currently defined European law.

It would not be practical or economical to file patent applications for each therapy generated from each patient so a more holistic approach is necessary and there are in fact a number of strategies that are suitable for patenting CAR-T therapies in Europe.

The above considerations highlight that with CAR-T therapies, as with any therapeutic invention, it is essential to put together a well thought out patenting strategy that considers all aspects of the therapy from how, where and by whom each step is carried out, to what reagents are used, where and how they are stored, and what aspects are common to all therapies, as opposed to those that are specific to the patient being treated.

At GJE our highly experienced patent attorneys in our biotechnology group will help you to develop an effective strategy to secure and protect your investment in this state of the art and rapidly developing technology. Of course, the intense interest in this area and the challenges highlighted above mean that a crowded patent landscape is developing. Our attorneys will also help you navigate through this and find a path to enable you to successfully develop and commercialise this technology.

To discuss your biotechnology intellectual property strategy, get in touch with Ross Cummings via ross.cummings@gje.com.