CAR T cell therapies: Review of EPO decisions

Adoptive T cell therapies, including chimeric antigen receptor (CAR) T cell therapies, T cell receptor (TCR) therapies, and tumour infiltrating lymphocyte (TIL) therapies, have emerged as a transformative class of cancer immunotherapy. Such therapies function by enhancing the activity of T lymphocytes and other effector cells to mount an antitumour immune response.

Given their relatively recent development, European case law specifically addressing these technologies remains limited. However, a developing body of decisions from the EPO Technical Board of Appeal is beginning to define how core patentability requirements apply to these complex and modular therapies. Such decisions are discussed below.

T 1502/22 (CD33-specific CAR/CELLECTIS)

The claim in question related to an engineered immune cell expressing a CD33-specific CAR for the treatment of various leukaemias and lymphomas.

The central issue was whether the claimed medical uses were sufficiently disclosed under Article 83 EPC.

The Board referred to the established case law, T 19/90, which teaches that an objection for lack of sufficiency of disclosure needs to be based on serious doubts substantiated by verifiable facts.

The application contained experimental data demonstrating activation and cytotoxic activity of T cells expressing the claimed anti-CD33 CAR against CD33-positive cells. The Board found this sufficient to establish a credible therapeutic effect and create a strong presumption that the claimed treatment would work. The Board stated that “the opponent in such case bears the burden of proving insufficiency of disclosure and rebutting this presumption."

The Board concluded that the opponent had provided no evidence showing that the skilled person at the effective date would have had doubts as to whether the tumours listed in the claims could be treated with an anti-CD33 CAR, and that there was no evidence on file that any of the cancers recited in the claim do not express CD33.

The opponent argued that two cell lines used in the patent were derived only from two cancer types. The Board concluded that, in view of the known mechanism of activity of CAR T cells (document D16), the experimental results in the application as filed, and the teaching of the application as a whole (which reported CD33 expressed on cells of myeloid lineage and some lymphoid cells), the skilled person at the relevant date would have considered it credible that the therapeutic effect could be achieved for cancers of both myeloid and lymphoid lineage.

The opponent also argued that the claim was not limited to CD33-expressing cells. However, the Board also considered that, for CAR T cell therapy, the common general knowledge of the skilled person included that the action of CAR T cells against cancer required binding to a target on a cancer cell. They would thus have understood that the cytolytic activity, i.e. the therapeutic effect, could only be achieved in cells expressing CD33. The Board also referred to the established case law (T 190/99 and T 596/96) that teaches that a claim has to be interpreted in a technically sensible way ruling out illogical interpretations.

Thus, the claimed invention was found to be disclosed in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art.

Take-home message:

The decision confirms a relatively permissive approach to sufficiency for claims directed to CAR T cell therapies. In particular, broad medical use claims may be allowable where the experimental results and teaching of the application as a whole make it credible to the skilled person that the claimed invention would have a therapeutic effect.

T 0203/22 (Targeting B7-H6/DARTMOUTH COLLEGE)

With respect to the CAR T cell therapy, the claims in question related to a CAR targeting the tumour antigen B7-H6.

The central issue was whether the claimed CAR was obvious under Article 56 EPC.

Applying the problem-solution approach, the Board’s reasoning was as follows:

Closest prior art: Document D12 was selected as the closest prior art because it related to the same purpose and disclosed an NKp30-based CAR demonstrating anti-tumour activity in lymphoma. NKp30 is a natural cytotoxicity receptor that targets B7-H6, as well as other ligands such as BAT3 and pp65 proteins.

Difference: The Board concluded that the difference was the replacement of the NKp30 receptor extracellular domain with an antibody-derived binding domain specific for B7-H6.

Technical effect: The patent demonstrated that treatment with the claimed anti-B7-H6 CAR T cell led to increased T cell activation (IFNgamma; Figure 2A) and improved survival (Figure 5B) compared with treatment with the NKp30 CAR T cell.

The Board concluded that the appellants did not present any evidence demonstrating that the reported effects could only be observed for the specific combination of scFv, hinge domain and intracellular signaling domain(s) tested in the patent in suit. Thus, the data was considered proof of concept that the specific targeting of B7-H6 results in improved anti-tumour activity when compared to the more unspecific targeting by NKp30-based CAR.

Objective technical problem: The problem was therefore defined as providing an improved B7-H6-targeting CAR.

Obviousness assessment: The Board acknowledged that B7-H6 was known to be expressed on human tumour cells and thus it might have been expected that replacement of the NKp30 in document D12 by a more specific ligand would lead to a reduced reactivity against normal cells or dendritic cells (i.e. on-target off-tumour cells).

The Board also acknowledged the production of B7-H6-specific antibodies capable of blocking NKp30 CAR-dependent T cell activation had been disclosed in document D11, and that such anti-B7-H6 antibodies can be assumed to be suitable for constructing a CAR.

The structure of CARs was considered to be common general knowledge (document D6).

Nevertheless, the Board concluded that “the skilled person would not have expected the improved IFNgamma production [or survival] observed with anti-B7-H6 CAR T cells compared with NKp30 CAR T cells in response to B7-H6-expressing cells."

The Board concluded that the skilled person would not have arrived at the claimed subject matter based on the disclosures of the prior art. The claims were therefore found to be inventive.

Take-home message:

The decision demonstrates that broad claims directed to CAR T cell therapies may succeed on inventive step if supported by an unexpected technical effect, even where the underlying CAR architecture and target antigen are already known.

T 1555/23 (CAR T cell toxicity management/TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA)

The patent in question related to a treatment regimen involving administration of CAR T cells followed by administration of an IL-6 inhibitor, such as tocilizumab, to manage therapy-related toxicity based on post-treatment cytokine monitoring. The tumour antigen targeted by the CAR was not defined in the claim.

The decision addressed several issues, including claim interpretation, priority entitlement, sufficiency of disclosure and inventive step.

Claim interpretation:

The Board interpreted claim 1 using a reasonable and technically “sensible” reading of the claim language in light of the description and the common general knowledge of the skilled person. This approach informed the Board’s interpretation of the IL-6 inhibitory compound, the management of CAR T cell-related toxicity, and the sequence of treatment steps.

Priority (Article 87 EPC) and Sufficiency of disclosure (Article 83 EPC)

The Board confirmed that entitlement to priority requires both direct and unambiguous disclosure and an enabling disclosure that, for further medical use claims, renders the claimed therapeutic effect credible.

The Board found that the priority document, together with common general knowledge regarding CAR T cell therapies, provided a credible basis for the claimed management of CAR T cell-related toxicity. As the opponents failed to raise serious doubts substantiated by verifiable facts, both priority and sufficiency were acknowledged.

Inventive step (Article 56 EPC):

Document D23 was chosen as the closest prior art as it discloses a treatment of cancer patients with CAR T cells as defined in claim 1. The Board concluded that the difference between the claimed invention and document D23 was (i) the monitoring of cytokine (including IL-6) levels to determine an appropriate second-line therapy, and (ii) the use of an IL-6 inhibitory compound as a second-line therapy.

The Board found that the differences provided an improvement over corticosteroid treatment. The objective technical problem was thus formulated as the provision of an improved CAR T cell therapy of cancer.

The Board found that none of the cited documents disclosed IL-6 inhibition as a strategy for managing toxicities associated with CAR T cell therapy. Thus, the claims were considered to be inventive over the prior art.

Take-home message:

The decision confirms that established principles governing medical use claims apply equally to emerging cell and gene therapy technologies such as CAR T cell therapies. In particular:

1. therapeutic efficacy is assessed primarily under sufficiency rather than inventive step;
2. the credibility of the claimed therapeutic effect can be supported by common general knowledge and post-published evidence; and
3. a successful sufficiency attack requires serious doubts substantiated by verifiable facts.

T 0250/24 (MND promoter/2SEVENTY BIO)

The patent in question related to a lentiviral vector encoding a CAR that binds to BCMA.

The central issue was whether the amended claims added subject matter beyond the original disclosure under Article 123(2) EPC.

The Board found that claim 1 required multiple selections from different lists, namely (a) BCMA as the target antigen, (b) the CD8 hinge region, and (c) the CD137 co-stimulatory domain, and that there was no pointer to this specific combination of features in the application as filed.

Although similar constructs appeared in the Examples, those examples contained additional features that were absent from the claims. The Board therefore held that the claim constituted an “impermissible intermediate generalisation” and thus added subject matter.

Take-home message:

The decision demonstrates that, for CAR T cell inventions, which involve multiple interchangeable domains, explicit disclosure of preferred combinations of CAR components is critical during patent drafting. Failure to disclose relevant combinations directly may significantly restrict amendment options later in prosecution or opposition proceedings.

Conclusions

Taken together, these decisions suggest that the EPO is broadly supportive of innovation in adoptive T cell therapies, and is prepared to allow meaningful claim breadth where supported by credible technical teaching. However, this flexibility is balanced by a strict approach to claim amendments and disclosure requirements. As a result, strong technical support and careful drafting remain critical to securing robust protection.

In practice, this means that for CAR T cell inventions (and, by analogy, TCR- and TIL-based inventions):

1. Applicants may be able to secure broad claims on the basis of robust experimental data where the mechanism of action and therapeutic effect are shown to be credible, unless there are serious doubts as to whether the technical effect can be achieved over a particular part of the claim scope;
2. The Board appears to be willing to take into account the common general knowledge surrounding CAR T cell technology when assessing claim interpretation, sufficiency of disclosure, and inventive step; and
3. Applicants should include detailed structural disclosure of preferred combinations and fallback positions to mitigate the risk of added matter objections.

As the field continues to evolve, the interplay between functional breadth and structural specificity is likely to remain a central consideration in both securing and defending patent protection for adoptive T cell therapies.

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