# US 12,760,117 B2 · Nanobody target MSLN and uses in chimeric antigen receptor cell therapy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,760,117 B2 - Document ID: US12760117B2 - Status: Granted - Kind: B2 - Application number: 18/540,269 - Filed: 2023-12-14 - Published: 2024-06-20 - Granted: 2026-10-13 - Earliest claimed: 2022-12-14 - Assignees: Innovative Cellular Therapeutics Holdings, Ltd.; Innovative Cellular Therapeutics, Inc. - Applicants: Innovative Cellular Therapeutics Holdings, Ltd.; Innovative Cellular Therapeutics, Inc. - Inventors: Xiaogang Shen; Wensheng Wang; Xudong Tang; Chengfei Pu; Zhao Wu; Lei Xiao - Web page: https://patentgrep.com/patent/US12760117B2 ## CPC - C07K 16/32: against translation products of oncogenes - A61K 47/6851: {the antibody targeting a determinant of a tumour cell} - A61K 51/1045: {against animal or human tumor cells or tumor cell determinants} - A61P 35/00: Antineoplastic agents - C07K 14/7051: {T-cell receptor (TcR)-CD3 complex} - C07K 14/70517: {CD8} - C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)} - C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex} - C12N 5/0636: {T lymphocytes} - C07K 2317/31: multispecific - C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody® - C07K 2319/03: containing a transmembrane segment - C12N 2502/30: tumour cells - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract The present disclosure describes compositions and methods for treating solid tumors expressing mesothelin (MSLN) using chimeric antigen receptor (CAR) T cell therapy. The compositions comprise CARs with an extracellular domain that specifically binds MSLN. The extracellular domain comprises a single variable domain (VHH) antibody that targets MSLN. Polynucleotides encoding the anti-MSLN CAR constructs are provided. Pharmaceutical compositions comprising CAR T cells expressing the anti-MSLN CARs are also described. The CAR T cells demonstrate cytotoxicity against MSLN-expressing tumor cells in vitro and anti-tumor activity in vivo. Methods are provided for generating the CAR T cells by transfecting T cells with lentiviral or retroviral vectors carrying anti-MSLN CAR encoding sequences. The anti-MSLN CAR T cell therapy described herein provides an effective approach for treating solid tumors expressing MSLN, such as mesothelioma, ovarian cancer, pancreatic cancer, and lung cancer. ## Claims ### Claim 1 An antibody that binds mesothelin (MSLN), where in the antibody comprises a VHH domain comprising one of SEQ ID NOs: 1-10. ### Claim 2 (depends on 1) The antibody of claim 1, wherein the antibody comprises SEQ ID NO: 8 or 9. ### Claim 3 (depends on 1) The antibody of claim 1, wherein the antibody is a single domain antibody. ### Claim 4 (depends on 1) The antibody of claim 1, wherein the antibody is conjugated to a cytotoxic agent. ### Claim 5 (depends on 4) The antibody of claim 4, wherein the cytotoxic agent is a radioactive isotope or a toxin. ### Claim 6 (depends on 1) The antibody of claim 1, wherein the antibody is a bispecific antibody comprising the VHH domain, a linker, and an antibody binding CD3. ### Claim 7 (depends on 1) A polynucleotide that encodes the antibody of claim 1. ### Claim 8 (depends on 7) A modified cell comprising the polynucleotide of claim 7. ### Claim 9 (depends on 3) A chimeric antigen receptor (CAR) comprising an extracellular domain comprising the antibody of claim 3. ### Claim 10 (depends on 9) The CAR of claim 9, wherein the CAR comprises a transmembrane domain and an intracellular domain. ### Claim 11 (depends on 10) The CAR of claim 10, wherein the intracellular domain comprises a co-stimulatory signaling region that comprises an intracellular domain of a co-stimulatory molecule comprising at least one of CD27, CD28, 4-1BB, OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, and B7-H3. ### Claim 12 (depends on 9) The CAR of claim 9, wherein the CAR comprises one of SEQ ID NO: 11-20. ### Claim 13 (depends on 9) A polynucleotide that encodes the CAR of claim 9. ### Claim 14 (depends on 13) A modified cell comprising the polynucleotide of claim 13. ### Claim 15 (depends on 14) The modified cell of claim 14, wherein the modified cell is a T cell or NK cell. ### Claim 16 (depends on 14) A composition comprising a population of the modified cells of claim 14. ### Claim 17 (depends on 16) The composition of claim 16, wherein the modified cells have reduced expression of endogenous T cell receptor alpha constant (TRAC) gene. ### Claim 18 (depends on 16) The composition of claim 16, wherein the modified cells comprise a polynucleotide encoding hTERT, a nucleic acid encoding SV40LT, or a combination thereof. ### Claim 19 (depends on 16) The composition of claim 16, wherein the modified cells comprise a polynucleotide encoding a cytokine. ### Claim 20 (depends on 16) The composition of claim 16, wherein the CAR comprises one of SEQ ID NO: 11-20. ### Claim 21 (depends on 16) The composition of claim 16, wherein the modified cells comprise a polynucleotide encoding at least one of IL-6, IFNγ, IL-12, and IL-2.