http://ipkitten.blogspot.com/2025/03/beyond-process-securing-ip-protection.html
Cell therapy represents one of the most exciting fields of innovation, with the potential to provide long-term cures for previously incurable diseases. However, unlike traditional pharmaceuticals, these “living medicines” present unique IP challenges that can make or break a biotech’s future. Whilst conventional pharmaceuticals benefit from straightforward composition of matter patents that protect their chemical structure or biological sequence, cell therapies are vastly more complex and heterogeneous. It is therefore common for companies to define and protect their cell therapy innovations with patents for the manufacturing process. However, manufacturing IP has many intrinsic pitfalls, and is often not considered by investors to provide adequate exclusivity and surety of return of investment. How then should companies define and protect their innovative cell therapies?
Challenges for cell therapy IP strategy: How to define the product?
IP strategy for cell therapy presents unique challenges. The critical question for IP strategy in the cell therapy field is how the product should be defined. Without a good product definition, protecting the product becomes a far greater challenge.
| Cell therapy |
The primary aim of IP strategy within the pharmaceutical field is a whole is to provide cast-iron IP protection for the drug product. Bringing a new chemical entity or biologic to market for the treatment of a certain disease can take a decade or more. Throughout this process, the chemical structure or biological sequence of the drug must be disclosed for regulatory purposes. Patent protection is therefore absolutely critical to ensure return of investment. The most important patent within the IP portfolio for a drug product is therefore the composition of matter case which protects the product itself, e.g. the chemical structure or sequence of the molecule. However, unlike other biologic drugs such as monoclonal antibodies, cell therapy products cannot be fully defined by a biological sequence. Cell therapies therefore represent a challenge for innovators seeking to define and protect their products.
Not all cell therapy products can be protected by traditional composition of matter IP
To understand the challenges for IP protection of cell therapies, it is helpful to look at one of the most common types of cell therapy currently in the clinic, CAR-T cells. These products comprise a T cell engineered to express a Chimeric Antigen Receptor (CAR) that directs the T cell to cellular targets in the body, such as cancer cells. In CAR-T cell therapies, the CAR is a molecule very similar to a monoclonal antibody. Various aspects of the product can therefore be claimed in patent, including the CAR amino acid sequence, DNA vectors encoding the CAR and cells comprising the vector. These types of claim provide a level of composition of matter protection for a CAR-cell therapy product.
However, looking beyond CAR-cell therapies, there are also many types of cell therapy that do not comprise an easily definable biological molecule such as a CAR. Some cell therapy products, for example, consist only of stem cells differentiated into certain cell types using standardised and highly optimised protocols. For these cell therapies, companies have often sought to protect the manufacturing process itself. This strategy is not surprising given that the manufacturing process for certain cell types is often the scientific problem the company is focussed on solving.
Indeed, a popular mantra in the field of cell therapy is that “the product is the process”. This is because, in cell therapy, the quality, safety, and efficacy of the final cell product is generally intrinsically linked to and determined by the manufacturing process. The process used to grow and differentiate cells into the cell therapy product will largely define what the product is and how it will perform clinically. Innovation in the cell therapy field therefore focuses intensely on process development, standardisation, and careful control of manufacturing conditions. It is therefore not surprising that a common strategy for protecting cell therapy inventions is manufacturing or process IP. However, manufacturing IP is not necessarily the only or even best way to protect such products.
Case study: Regenerative heart cell therapy
An interesting cell therapy product for which the key innovation lies in the process development was described a recent Nature paper. The cell therapy is a treatment for regenerating cardiac tissue in heart disease patients. The challenge for using cell therapy for heart regeneration is ensuring that the new cells and tissue integrate and beat in-time with the existing tissue. The paper presents clinical data from a single patient suffering from multiple cardiac conditions including coronary heart disease, heart failure, and a previous myocardial infarction. The patient received engineered heart muscle patches constructed from 400 million heart cells and connective tissue. The patient underwent heart transplantation after about 3 months, which provided the researchers with the opportunity to analyse the implanted patches. The paper reports that the cardiac cells were retained and that there was minimal immune reaction, This was in line with the improved cardiac function that had been observed over the 3 month period, and supported the continuation of the trial in other patients (currently ongoing). The inventors of the heart regeneration therapy have also founded a company, Repairon, focused on the clinical development of engineered heart muscle cell therapy products.
So how is Repairon protecting its IP? A quick Google Patent search reveals that Repairon has about six published patent families relating to various aspects of the processes for manufacturing their regenerative heart cell therapy technology. These patent families include a method of changing culture medium of a suspension culture (WO2021116361), a method of expanding pluripotent stem cells (PSC) in suspension culture in a bioreactor (WO2021116362) and a method of producing a population of immune cells from pluripotent stem cells comprising multiple culturing steps in the presence of specific growth factors (WO2023001833). In line with the strategy taken by similar regenerative cell therapy companies, Repairon thus appears so far to have focused on protecting its manufacturing and process IP.
The problem with process patents
Whilst in many cases manufacturing IP readily maps onto the innovation process behind regenerative cell therapy products, manufacturing and process IP also comes with many potential pitfalls (see also The benefits and pitfalls of drug manufacturing IP (T 2543/22)). Most problematically for early-stage companies, manufacturing patents are often vulnerable to design-around strategies by competitors. This is especially true in the biologically complex field of cell therapy, where there can be many different ways of achieving the same functional outcomes. The processes for generating a cell therapy product will also likely evolve over time, such that the highly specific process described in an early-stage patent filing may be long out of date by the time the product reaches the clinic. Whilst a second patent application could be filed for the new process, the prior application may be citable against the inventiveness of the later process.
Additionally, even if the patent still protects the process behind the clinical product, detecting and proving infringement of a manufacturing patent can also be exceedingly difficult for a patent holder. Faced with all of these challenges, there is a strong argument that truly innovative manufacturing IP for cell therapies may be best protected by trade secrets rather than patents.
Product patent for cell therapies
Despite the necessary focus on the process development in the field of cell therapy, process patents do not guarantee strong protection of the product. Meaningful patent protection for a cell therapy, as with any other drug product, must clearly cover and protect the clinical product, not just one process by which the product may be made. But is this possible? Surprisingly, despite the current focus on process IP in the field, there are many opportunities for cell therapy products per se, even for regenerative cell therapies. Whilst cell therapies are inherent heterogeneous, regulatory authorities already stipulate certain important cell therapy product characteristics that must be satisfied before a cell therapy product is administered to a patient. These characteristics are often the result of the manufacturing process, but may be defined in and of themselves.
Examples of definable cell therapy product criteria used by regulatory authorities include the expression of certain cell surface proteins indicative a certain cell therapy (i.e. demonstrating the cells are correct type of cells), and gene expression markers indicative of a fully differentiated cell that will not grow into the wrong type of cell when implanted into the body. In order to guarantee safety and efficacy, another company making a similar cell therapy product to one that is already in the clinic will have to satisfy the same product criteria. The gene and protein expression markers of a cell therapy product becomes the cell therapies product signature, akin to the sequence of an antibody, or the chemical structure of a small molecule pharmaceutical. These clearly definable product characteristics may thus also be used as the inventive features of a cell therapy product in a commercially relevant patent claim.
Crucially, the gene and protein expression signatures of a cell therapy product may only become apparent or finalised at the IND stage shortly prior to phase I, often in discussions with the relevant regulatory authorities. It is therefore critical that patent filings for such products align with the regulatory interactions.
Final thoughts
Cell therapy remains one of the most promising and challenging frontiers in modern medicine, requiring equally innovative approaches to IP protection. Whilst the “product is the process” mantra has guided many companies’ IP strategies so-far, relying solely on process patents leaves significant vulnerabilities. Cell therapy companies should pursue a comprehensive approach that includes product-based protection defined by the unique cellular characteristics of their cell therapy product required for regulatory approval. By focusing on these measurable signatures, companies can establish stronger composition of matter-like protection for their cell therapies. This approach, combined with strategic trade secret protection for manufacturing know-how, offers cell therapy innovators the best chance to secure meaningful exclusivity and ensure return of investment in this rapidly evolving field.
Further reading
- Strict US written description requirement applied to CAR-T-cell therapy (Juno v Kite) (Jan 2022)
- Falling between the cracks: The challenges of patent strategy for stem cell therapies (T 1259/22) (Aug 2024)
- The benefits and pitfalls of drug manufacturing IP (T 2543/22) (Feb 2022)
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