Intellectual Property Considerations in Cell Therapy Developments – An EPO Perspective

By Gilles Pfend, Ph.D., European and Swiss Patent Attorney and Ricardo Martin, Ph.D., European Patent Attorney – Katzarov, Patent & Trademark Attorneys

The Expanding Intellectual Property Landscape of CAR-T Cell Therapies

The rapid evolution of cell therapies, in particular chimeric antigen receptor T (CAR-T) cell therapy, has generated a dense and increasingly complex intellectual property (IP) landscape.

According to statistics from the European Patent Office (EPO) published in 2019, the number of patent filings relating to CAR T-cell therapies increased sharply between 2013 and 2019, with a steady year-on-year rise in new applications. Since 2019, this upward trend has continued, with more than 700 patent families being filed annually worldwide. Updated EPO data further indicate that the leading applicants in the CAR T-cell field predominantly originate from China and the United States, while China, the PCT (Patent Cooperation Treaty) route, and the United States remain the most frequently selected filing jurisdictions.

Within the context of this publication, we will focus on the example of CAR-T cells. Recent scientific advances addressing CAR-T limitations and in vivo engineering strategies highlight several recurring areas of innovation: (i) in vivo CAR delivery, (ii) manufacturing optimization and enrichment of memory stem cells, (iii) armored CAR constructs with for example cytokine co-expression, (iv) strategies to mitigate resistance, and (v) modulation of exhaustion and cytotoxicity (increased CAR T-cell survival).

Based on our expertise, each of these innovation axes presents distinct challenges in terms of patentability under the European Patent Convention (EPC), as well as potential issues regarding freedom-to-operate (FTO) and enforceability.

Patentability Hurdles in Next-Generation CAR Design

A first consideration concerns the increasingly crowded prior art landscape surrounding CAR architecture. Foundational elements such as scFv-based binders (notably against CD19), hinge and costimulatory domains, cytokine-armored formats, and standard autologous manufacturing workflows are extensively disclosed. Novelty may often be acknowledged for specific structural configurations; however, inventive step will depend on whether the distinguishing features credibly solve a technical problem over the closest prior art.

Applications directed to in vivo CAR delivery using targeted vectors or lipid nanoparticles introduce further complexity. At the EPO, broad functional claims risk objections under Articles 83 and 84 EPC if the disclosure does not enable the skilled person to achieve the claimed effect across the entire scope. The requirement of plausibility, as established by the Enlarged Board of Appeal of the EPO (G 02/21), is particularly important when therapeutic effects are claimed. The description must provide sufficient technical detail and examples to make the asserted therapeutic effect credible. Without supporting experimental data, the inventive step may be challenged either during examination at the EPO or later in opposition on the basis that the technical effect relied upon was not rendered plausible as of the filing date.

Process innovations relating to manufacturing efficiency and enrichment of T memory stem cell (TSCM) populations raise distinct issues. Where the contribution lies in producing a CAR-T composition enriched in a defined TSCM subset, it may be advantageous to formulate product claims characterized by measurable biological or physiological parameters (such as specific expression markers or an unexpected and/or enhanced phenotype), provided that such parameters are clearly defined, reproducible and not-present in TSCMs of the prior art.

Moreover, inventive step will depend on whether the skilled person, starting from known expansion protocols, would have reasonably expected that the claimed process parameters lead to the asserted enrichment effect.

Patentability of CAR constructs, including armored CAR-T cells co-expressing cytokines, must be assessed against extensive prior disclosures of fourth-generation CAR-T cells. The mere addition of, e.g. a cytokine molecule, may not suffice to establish inventive step if the prior art already suggests cytokine co-expression to enhance persistence or modulate the tumor microenvironment. Under the EPO’s problem-solution approach, the objective technical problem must be formulated in light of the closest prior art, and the application should contain evidence that the specific cytokine choice, expression configuration, or affinity tuning produces a technical effect that goes beyond a predictable enhancement of T cell activity. The EPO will scrutinize whether the skilled person, faced with issues such as relapse, antigen escape, or T cell exhaustion, would have considered the claimed modification as an obvious alternative. Comparative examples (think of referenced CAR T cell construct or standard) are likely to play a crucial role in the EPO’s evaluation.

Avoiding Added Subject-Matter in CAR-T Prosecution

An additional structural consideration concerns added subject-matter under Article 123(2) EPC. In rapidly evolving technology platforms where multiple variants are contemplated, amendments during prosecution must remain strictly within the content of the application as filed.

Integrating FTO Analysis into CAR-T Development Strategy

The field is characterized by a dense patent landscape in which key components such as CD19 binders (e.g. scFv), intracellular signaling domains (e.g. CD3z), transmembrane domains, costimulatory domains including CD28 and 4-1BB, and lipid nanoparticle (LNP) delivery systems may be subject to third-party rights. As a result, even technically differentiated products may face infringement risks at the level of individual subcomponents or enabling technologies. An effective innovation strategy should therefore combine early and iterative FTO assessments, particularly before significant clinical investment, with a layered patenting approach covering compositions, methods of manufacture, and therapeutic uses.

Conclusion

In conclusion, cell therapy and in particular next-generation CAR-T innovations operate within a technically unpredictable yet legally stringent environment under the EPC. Successful protection before the EPO requires a carefully substantiated technical effect, precise structural definition of distinguishing features, and examples evidencing the unexpected technical effects of these distinguishing features. In this field, inventive step will often turn not on the conceptual ambition of the technology, but on the quality and specificity of the experimental evidence supporting the claimed solution.

Furthermore, given the complexity of CAR T-cell manufacturing processes which often rely heavily on proprietary know-how and the difficulty in precisely identifying specific cell expression markers, maintaining certain aspects of the technology as trade secrets may, on a case-by-case basis, represent a strategically preferable approach to preserving competitive advantage.

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