Timothy Au

Cancer immunotherapy is an exciting, relatively new therapy that treats cancer by unleashing the power of the immune system. It has been hailed as one of the most promising advances in the treatment of cancer in recent times.

Immuno-oncology research is growing at a rapid pace and for the last three years this has begun to translate into a patenting frenzy as players seek to stake their claim in this wide commercial landscape. In this month’s piece from Clarivate Analytics, Bob Stembridge – the company’s marketing communications manager – looks at what the data is telling us.

Immunotherapy has become the major driver behind deal making in the pharmaceutical industry with 32 of the 35 multi-billion deals in the last five years being focused on immuno-oncology. In a recent webinar, my colleague Anette Breindl and I reviewed recent trends in oncology deals, the science behind immuno-oncology and the rapidly moving patent landscape to identify the key technology areas and major players in this fast-moving therapy area.

How immunotherapy works

Conventional cancer therapies include radiation, surgery and chemotherapy. These kill cancerous cells, but also damage healthy cells or nearby tissues. Immuno-oncology presents a whole new treatment paradigm: it tunes the immune system to specifically fight cancer cells. When it is successful, this approach can lead to very long-term remissions compared to conventional treatments, which often work for a time but cannot ultimately prevent relapse.

Over the years, cancer has evolved some sneaky tricks to avoid detection and attack by the immune system, thus allowing cancer cells to proliferate without hindrance.  In cancer, there are small ligands on the surface of the cell which trick the immune system into believing they are healthy cells and thus evade attack. Immunotherapy drugs work by binding to those ligands thus exposing the cancer cells for the foreign bodies they are and enabling the immune system to recognize and deal with them accordingly.

There are now a number of different drugs on the market that work this way. The most promising ones are what are called checkpoint inhibitors, antibodies to PD1, its ligand PDL1, and CTLA4. Those antibodies can either turn on immune cells (CTLA4) or prevent them from being turned off (PD1 and PDL1).

The first checkpoint blocker, Yervoy, targets CTLA4 and was approved by the FDA for treatment of melanoma in 2011. It has proven very effective for some patients. In clinical trials, patients whose life expectancy at the moment they entered the trial was measured in months were cured by the treatment. The very first patient who received Yervoy, in 1999, is still alive today.

A more recent development is called Chimeric Antigen Receptor T-cell (CAR T-cell) therapy which is based on the simple concept of taking a patient’s own T cells, engineering them to target a particular cancer, multiplying them in the lab and then infusing them back into the patient.  It’s a very personalised approach to cancer treatment.  It’s also in very early stages, but it’s showing a lot of promise.

The first two CAR T cells, Kymriah and Yescarta, were approved by the FDA for acute lymphoblastic leukemia just last year in 2017. Kymriah was both the first CAR T cell and the first gene therapy to be approved by the US FDA.

Trends in oncology dealmaking

Oncology continued to dominate the dealmaking landscape for therapeutics in 2017, driven by the expected growth in the market.  EvaluatePharma has forecast that it will remain the highest grossing therapy area until 2022, expanding at a compound annual growth rate of more than 12% to reach a value of almost $220 billion.

The 2017 deal between AstraZeneca and Merck & Co in the area of PD1/PD-L1 small molecule combinations is the largest recorded within the past five years, but there are an additional 34 deals in this time period with a total value in excess of $1 billion. Of these 35 deals, 32 are focused on immuno-oncology, and many involve emerging platforms, such as chimeric antigen receptor (CAR) T cell therapies.

A review of oncology dealmaking from 2013 to 2017 shows a steep rise in activity during the first three years of this period (Figure 1). One important contributor to this increase could be the approval of the first two PD1–PDL1 checkpoint inhibitors - Merck & Co’s Keytruda (pembrolizumab) and Bristol-Myers Squibb’s Opdivo (nivolumab) - in the second half of 2014. This accelerated a wave of dealmaking, not only around other checkpoint inhibitors, but also for molecules and technologies that could offer synergistic benefits when used in combination with these drugs.

Figure 1:  Licensing, joint venture and research-only oncology deals by volume and value from 2013 to 2017

Source: Cortellis

Immuno-oncology patent landscape

The growth in patenting in immuno-oncology has been explosive over the last three years.  Figure 2 shows the volume of DWPI families in six checkpoint inhibitor targets (CTLA-4, PD-1, PD-L1, Ox40, TIM3 and LAG3) and CAR T-cell therapy from 2008-2018.  Numbers for 2018 are, of course, incomplete, but projecting these forward, we see continuing growth rates of between 124% for CAR T and 234% for PD-L1 closely followed by PD-1 at 220% growth over 2017.

Figure 2: Immuno-oncology patent families 2008-2018

Source: Derwent Innovation (DWPI)

A comparison of the number of scientific papers to the number of patent families over time shows clearly the transition from discovery to protection with the intent to commercialise this technology (Figure 3). 

The volume of scientific papers published grew rapidly from 2014 to 2017 but growth appears to be slowing slightly in 2018, whereas the volume of patent families seems set to continue to grow increasingly quickly through 2018 and beyond.

Figure 3: Scientific literature and patent family volumes 2008-2018

Source: Derwent Innovation (Web of Science & DWPI)

Across all therapy areas, the major players in immuno-oncology are given in Figure 4.

Figure 4:  Top 10 assignees for all patent families relating to immuno-oncology

Source: Derwent Innovation (DWPI)

The patent portfolios in immuno-oncology for the seven top assignees by patent family volume are mapped in Figure 5. The thematic concept map is produced with ThemeScape within Derwent Innovation. It uses advanced text analysis software to summarise the major concepts and subject matters within the published documents in the patent collection.

The data set was compiled by searching for immuno-oncology patents in Cortellis and transferring the target list of patent numbers from Cortellis to Derwent Innovation to run patent analysis there.

This shows various areas of focus for each company across the immuno-oncology landscape with, for example, the University of Pennsylvania occupying the top left hand corner of the map where CAR T-cell therapy inventions are located.  A number of these overlap with Novartis (these are white dots) which reflects the 2012 licensing agreement between University of Pennsylvania and Novartis for CAR T-cell therapy.

Further discussion and analysis of the science behind immuno-oncology and the rapidly developing immuno-oncology patent landscape is available from a recording of the webinar here.

The full report of “Trends in immuno-oncology dealmaking” is available here.

IAM and Clarivate Analytics, the world-leading provider of patent information, have partnered to provide IAM's readers with exclusive insight and analysis of globally important IP business issues.