FB Rice

Prue Crown B

The cancer treatment landscape has evolved from drugs that non-specifically target all rapidly dividing cells - chemotherapies, to drugs that target specific mutated forms of normally occurring proteins - targeted therapies, to drugs that enhance a person’s own immune system’s ability to detect and kill cancer cells - immunotherapies, to using actual infused or transplanted human cells to kill the cancer - cell therapy. Many different cell types may be used for cell therapy to treat a variety of diseases, including stem cell-based (e.g., hematopoietic stem cells) and non-stem cell (e.g., lymphocytes or T cell) based therapies.

More recently, the development of chimeric antigen receptor (CAR)-T cell therapies has altered the treatment paradigm for blood cancers. Chimeric antigen receptor T cell therapy uses immune cells called T cells, which are genetically modified to carry proteins on their surface. They are called Chimeric Antigen Receptors. The receptors are “chimeric,” as they combine both antigen-binding and T-cell activating functions into a single receptor. The resulting CAR-T cell specifically targets and directs the killing of cancer cells.

The first six globally approved CAR-T cell therapies (Figure 1) were all autologous, meaning they use an individual’s own T cells. The benefits of using autologous cell therapies include less chance of immune rejection and long-term persistence of the cells in a patient’s body, allowing the chance to elicit a long-term response. Downsides to autologous cell therapy include longer “vein-to-vein time” (i.e., the time required to obtain T-cells, “weaponize” them, and reintroduce CAR-T cells) and difficulty in scaling this highly individualized process for mass market use.

Following approvals of 6 different autologous CAR-T therapies since 2017, tabelecleucel (Ebvallo®) was the first “off-the-shelf”/allogeneic (“non-self”) cell therapy to receive marketing approval by the European Commission in 2022i (Figure 1). The benefits of allogeneic cell therapies include quicker treatment times, as cells from donors of various HLA subtypes can be stockpiled and ready to treat patients once diagnosed, as well as a greater ability to scale for widespread commercial use. Downsides to allogeneic therapies include potentially shorter persistence of the cells in a patient’s body, limiting duration of responses, as well as a higher chance of immunological reaction against the donor cells and graft-versus-host disease.Figure 1: Cell therapy development and 1^st global approval timelines

Irrespective of the cell type used or condition to be treated, it is important that companies, whether it be startups, Big Pharma or contract manufacturers, and individuals (such as investors) working in the cell therapy space focus on patent strategy considerations to maximize market potential. Patent protection is granted for a limited period, generally 20 years from the filing date of the application. However, a recent analysis of clinical development times (i.e., number of years between first in human trials and approval) for US FDA-approved drugs over the last decade notes a stable median development time of 8.3 years, with many products taking upwards of 15 to 20 years. Effective patent strategy manages the tension between the challenging commercial realities of long development times and limited patent terms. 

In particular, an effective patent strategy in the cell therapy space requires monitoring R&D outputs at all stages of product development (i.e., pre-clinical, manufacturing, and clinical) to ensure opportunities for patent protection are identified and, if commercially relevant, pursued. Examples include: 

New compositions: “Composition of matter” claims are often viewed as the most valuable patent claims by investors in view of their potential breadth of coverage. This includes claims not only to the composition per se but also to structural components of the composition (e.g., safety switches and immune-checkpoint modulation (e.g., armored CAR-T cells)), altered functionality of the cells (e.g., T cells redirected for universal cytokine-mediated killing (TRUCKs)), off-the-shelf cell therapies and gene-edited cell therapies.

"Cell therapy represents an exciting and emerging new treatment model with the potential to help many patients."

Methods of manufacture: The manufacturing capability of cell therapies is critical, and there are currently few centers globally that can support commercial-scale cell therapy (particularly CAR T-cell therapy) production. Accordingly, there remains an enormous opportunity to leverage improvements in manufacturing methods and automation, for example, the production of off-the-shelf cell therapies, gene editing methods and devices or culture systems that include, e.g., integrated quality control measures (e.g., ability to track cell viability, cell number, cell identity, purity and/or potency).  

Methods of treatment: Method of treatment patents can protect approved therapies as well as new discoveries made after initial approval, like dosing regimens and treatment of new patient populations. New clinical indications, methods that offer more durable treatment responses, combination therapies or methods that reduce morbidity (e.g., reduced toxicity and/or side effects) are just some examples.

Understanding the patent landscape around individual therapies, including manufacturing processes and methods of use, through freedom-to-operate or landscape searching is also critical to any IP strategy. The type and extent of searching required are often dictated by a company’s budget, commercial activities, and objectives. However, whether you are a startup, a research institution, a contract manufacturer, an investor, or Big Pharma, patent landscape and freedom-to-operate analysis allow informed decisions to be made before investing considerable resources, such as time and capital, into product development and manufacturing. Early identification of blocking patents provides opportunities for mitigating risks, including design around, licensing opportunities or developing/mounting attacks against problematic patents.

Cell therapy represents an exciting and emerging new treatment model with the potential to help many patients. As such, it is also a crowded and rapidly evolving field with a market anticipated to reach four billion dollars by 2027. With this in mind, it’s critical for all stakeholders involved in the development of these therapies to consider their unique approach, including the pros and cons of their particular cell therapy and how these differentiating factors can be factored into a patent strategy to maximize the product’s exclusivity in the market post-approval.