Antibodies that specifically bind cldn6 or cd3 and bispecific antibodies that specifically bind cldn6 and cd3

{
  "publication_number": "US2026103514A1",
  "country": "US",
  "kind": "A1",
  "title": "Antibodies that specifically bind cldn6 or cd3 and bispecific antibodies that specifically bind cldn6 and cd3",
  "abstract": "Antibodies and antigen-binding fragments thereof that specifically bind CLDN6 or CD3, and bispecific antibodies and antigen-binding domains that specifically bind CLDN6 and CD3 are described. Also described are nucleic acids encoding the antibodies, compositions comprising the antibodies, methods of producing the antibodies, and methods of using the antibodies for treating or preventing diseases, such as cancer.",
  "claims": [
    "1. A bispecific antibody comprising a first antigen-binding domain that specifically binds Claudin-6 (CLDN6) and a second antigen-binding domain that specifically binds cluster of differentiation 3 (CD3), wherein the first antigen-binding domain comprises: a) a heavy chain complementarity determining region 1 (HCDR1), HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NOs: 2, 3 and 4, respectively, and b) a light chain complementarity determining region 1 (LCDR1), LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NOs: 5, 6, and 7, respectively. 2. The bispecific antibody of claim 1, wherein the first antigen-binding domain comprises: a) a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 8; and b) a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 9. 3. The bispecific antibody of claim 1, wherein the second antigen-binding domain comprises: a) a HCDR1, HCDR2, and HCDR3 comprising an amino acid sequence shown in SEQ ID NOs: 12, 13, and 14, respectively; and b) a LCDR1, LCDR2, and LCDR3 comprising an amino acid sequence shown in SEQ ID NOs: 15, 16, and 17, respectively. 4. The bispecific antibody of claim 1, wherein the first antigen-binding domain comprises: a) a VH comprising the amino acid sequence of SEQ ID NO:8; and b) a VL comprising the amino acid sequence of SEQ ID NO:9; and wherein the second antigen-binding domain comprises: c) a HCDR1, HCDR2, and HCDR3 comprising an amino acid sequence shown in SEQ ID NOs: 12, 13, and 14, respectively; and d) a LCDR1, LCDR2, and LCDR3 comprising an amino acid sequence shown in SEQ ID NOs: 15, 16, and 17, respectively. 5. The bispecific antibody of claim 1, wherein the first antigen-binding domain comprises: a) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO:10; and b) a light chain (LC) comprising the amino acid sequence of SEQ ID NO:11. 6. The bispecific antibody of claim 1, wherein the second antigen-binding domain comprises a single chain variable chain (scFv) comprising the amino acid sequence of SEQ ID NO: 18. 7. The bispecific antibody of claim 1, wherein the second antigen-binding domain comprises a HC comprising the amino acid sequence of SEQ ID NO:20. 8. The bispecific antibody of claim 1, wherein the first antigen-binding domain comprises: a) a VH comprising the amino acid sequence of SEQ ID NO:8; and b) a VL comprising the amino acid sequence of SEQ ID NO:9; and wherein the second antigen-binding domain comprises a scFv comprising the amino acid sequence of SEQ ID NO:18. 9. The bispecific antibody of claim 1, wherein the first antigen-binding domain comprises: a) a VH comprising the amino acid sequence of SEQ ID NO:8; and b) a VL comprising the amino acid sequence of SEQ ID NO:9; and wherein the second antigen-binding domain comprises a HC comprising the amino acid sequence of SEQ ID NO:20. 10. The bispecific antibody of claim 1, wherein the bispecific antibody comprises: a) a HC comprising an amino acid sequence of SEQ ID NO:10; b) a LC comprising an amino acid sequence of SEQ ID NO:11; and c) a scFv comprising an amino acid sequence of SEQ ID NO: 18. 11. The bispecific antibody of claim 1, wherein the bispecific antibody comprises: a) a HC comprising an amino acid sequence of SEQ ID NO: 10; b) a LC comprising an amino acid sequence of SEQ ID NO:11; and c) a second heavy chain (HC2) comprising an amino acid sequence of SEQ ID NO: 20. 12. The bispecific antibody of claim 1, wherein the first antigen-binding domain does not have cross-reactivity to human CLDN3, CLDN4 or CLDN9. 13. The bispecific antibody of claim 1, wherein the first antigen-binding domain specifically binds an epitope of CLDN6 (SEQ ID NO:1) comprising glutamine 156 (Q156). 14. The bispecific antibody of claim 1, wherein the second antigen-binding domain specifically binds an epitope of CD3ε (SEQ ID NO:23) comprising at least one amino acid in at least one of amino acid sequence selected from SEQ ID NOs: 27-31 and an epitope of CD3δ (SEQ ID NO: 22) comprising at least one amino acid in SEQ ID NO:32. 15. The bispecific antibody of claim 14, wherein the second antigen-binding domain specifically binds an epitope of CD3ε (SEQ ID NO:23) comprising at least one amino acid sequence selected from SEQ ID NOs: 27-31 and an epitope of CD3δ (SEQ ID NO:22) comprising SEQ ID NO: 32. 16. The bispecific antibody of claim 15, wherein the second antigen-binding domain specifically binds an epitope of CD3ε (SEQ ID NO:23) comprising SEQ ID NOs: 27-31 and an epitope of CD3δ (SEQ ID NO:22) comprising SEQ ID NO:32. 17. The bispecific antibody of claim 1, wherein the first antigen-binding domain binds CLDN6 with a K D of about 23 nM on CHO-CLDN6 overexpressing cells as measured by flow cytometry. 18. The bispecific antibody of claim 17, wherein the second antigen-binding domain does not bind cynomolgus monkey cells expressing cynomolgus CD3. 19. The bispecific antibody of claim 1, wherein the second antigen-binding domain binds CD3 with a K D of 10-100 nM as measured in a surface plasmon resonance assay at 25° C. 20. The bispecific antibody of claim 1, wherein the second antigen-binding domain comprises a single-chain antibody. 21. The bispecific antibody of claim 20, wherein the single-chain antibody comprises a single-chain variable fragment (scFv) comprising the amino acid sequence of SEQ ID NO:18. 22. The bispecific antibody of claim 21, which is an IgG1 subtype. 23. The bispecific antibody of claim 22 comprising an Fc domain, comprising one or more substitutions in the Fc domain that reduces Fc domain-mediated effector function, reduces binding to protein A, or improves bispecific antibody production. 24. The bispecific antibody of claim 23, wherein the one or more substitutions in the Fc domain, using residue numbering according to EU numbering, comprises H435R, Y436F, T366S/L368A/Y407V, T366W, S354C, Y349C, L234A, or L235A. 25. The bispecific antibody of claim 1, which binds both human T-cells and CLDN6 expressing cells. 26. The bispecific antibody of claim 1, which induces T-cell mediated cytotoxicity of CLDN6 + ovarian cancer cell lines. 27. The bispecific antibody of claim 1, which induces T-cell mediated cytotoxicity of OVCAR3 cancer cell lines. 28. The bispecific antibody of claim 1, which induces T-cell mediated cytotoxicity of PA-1 cancer cell lines. 29. The bispecific antibody of claim 1, which induces T-cell mediated cytotoxicity of OV-90 cancer cell lines. 30. The bispecific antibody of claim 1, which induces T-cell activation and proliferation. 31. The bispecific antibody of claim 1, which activates cytokine release. 32. A pharmaceutical composition comprising the bispecific antibody of claim 1 and a pharmaceutically acceptable carrier. 33. A pharmaceutical composition comprising the bispecific antibody of claim 3 and a pharmaceutically acceptable carrier. 34. An isolated nucleic acid encoding the bispecific antibody of claim 3. 35. A vector comprising the isolated nucleic acid of claim 34. 36. A host cell comprising the vector of claim 35. 37. A method of producing the isolated bispecific antibody of claim 1, comprising culturing a host cell of claim 36 under conditions to produce the bispecific antibody, and purifying the bispecific antibody. 38. An isolated antibody or antigen-binding fragment thereof that specifically binds CLDN6 comprising: a) a heavy chain complementarity determining region 1 (HCDR1), HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NOs: 2, 3 and 4, respectively, and b) a light chain complementarity determining region 1 (LCDR1), LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NOs: 5, 6, and 7, respectively. 39. The isolated antibody or antigen-binding fragment thereof of claim 38, wherein the isolated antibody or antigen-binding fragment thereof comprises: a) a heavy chain variable region (V H) comprising the amino acid sequence of SEQ ID NO: 8; and b) a light chain variable region (V L) comprising the amino acid sequence of SEQ ID NO: 9. 40. The isolated antibody or antigen-binding fragment thereof of claim 38, wherein the isolated antibody or antigen-binding fragment thereof comprises: a) a heavy chain comprising the amino acid sequence of SEQ ID NO: 10; and b) a light chain comprising the amino acid sequence of SEQ ID NO:11. 41. The isolated antibody or antigen-binding fragment thereof of claim 38, wherein the isolated antibody or antigen-binding fragment specifically binds human CLDN6 and does not bind human CLDN3, CLDN4 or CLDN9. 42. The isolated antibody or antigen-binding fragment thereof of claim 38, wherein the antibody or antigen-binding fragment thereof specifically binds an epitope of CLDN6 comprising glutamine 156 (Q156) of wildtype CLDN6 (SEQ ID NO:1). 43. The isolated antibody or antigen-binding fragment thereof of claim 38, wherein the isolated antibody or antigen-binding fragment binds human CLDN6 with a K D of about 23 nM on CHO-CLDN6 overexpressing cells as measured by flow cytometry. 44. An isolated nucleic acid encoding the antibody or antigen-binding fragment thereof of claim 38. 45. A vector comprising the isolated nucleic acid of claim 44. 46. A host cell comprising the vector of claim 45. 47. A method of treating a CLDN6 expressing cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 33. 48. The method of claim 47, wherein the CLDN6 expressing cancer is a solid tumor. 49. The method of claim 47, wherein the CLDN6 expressing cancer is ovarian, endometrial, testicular, liver, lung or gastric cancer. 50. The bispecific antibody of claim 1 for use in a method of treating a disease or disorder in a subject in need thereof. 51. The bispecific antibody for use of claim 50, wherein the disease or disorder is cancer. 52. The bispecific antibody for use of claim 51, wherein the cancer of claim 51, wherein the cancer is a CLDN6 expressing cancer. 52. The bispecific antibody for use of claim 52, wherein the cldn6 expressing cancer is a solid tumor. 53. The bispecific antibody for use of claim 52, wherein the cldn6 expressing cancer is ovarian, endometrial, testicular, liver, lung, or gastric cancer. 54. Use of the bispecific antibody of claim 1 in a method of treating a disease or disorder in a subject in need thereof. 55. The use of claim 54, wherein the disease or disorder is cancer. 56. The use of claim 55, wherein the cancer of claim 51, wherein the cancer is a CLDN6 expressing cancer. 57. The use of claim 56, wherein the CLDN6 expressing cancer is a solid tumor. 58. The use of claim 56, wherein the CLDN6 expressing cancer is ovarian, endometrial, testicular, liver, lung, or gastric cancer. 59. Use of the bispecific antibody of claim 1 in the manufacture of a medicament for treating a disease or disorder in a subject in need thereof. 60. The use of claim 59, wherein the disease or disorder is cancer. 61. The use of claim 60, wherein the cancer of claim 51, wherein the cancer is a CLDN6 expressing cancer. 62. The use of claim 61, wherein the CLDN6 expressing cancer is a solid tumor. 63. The use of claim 61, wherein the CLDN6 expressing cancer is ovarian, endometrial, testicular, liver, lung, or gastric cancer."
  ],
  "cpc": [
    "C07K 16/28",
    "A61K 2039/505",
    "A61P 35/00",
    "A61P 37/04",
    "C07K 16/2809",
    "C07K 2317/31",
    "C07K 2317/33",
    "C07K 2317/34",
    "C07K 2317/565",
    "C07K 2317/622",
    "C07K 2317/71",
    "C07K 2317/734",
    "C07K 2317/92"
  ],
  "filing_date": "2025-10-15",
  "publication_date": "2026-04-16",
  "application_number": "US-202519358808-A"
}