# US 2020/0399377 A1 · Combination cancer therapy with anti-cancer agents and antibodies targeting a complex comprising non-classical hla-i and neoantigen > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2020/0399377 A1 - Document ID: US20200399377A1 - Status: Published application - Kind: A1 - Application number: 16/975,364 - Filed: 2019-02-22 - Published: 2020-12-24 - Earliest claimed: 2018-02-23 - Assignees: Abexxa Biologics, Inc. - Applicants: AbeXXa Biologics Inc. - Inventors: Jon Weidanz - Web page: https://patentgrep.com/patent/US20200399377A1 ## CPC - C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules} - A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00) - A61K 39/001129: {Molecules with a "CD" designation not provided for elsewhere} - A61P 35/00: Antineoplastic agents - C07K 14/70517: {CD8} - C07K 16/2827: {against B7 molecules, e.g. CD80, CD86} - C07K 16/2887: {against CD20} - A61K 2039/507: {Comprising a combination of two or more separate antibodies} - C07K 2317/32: specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor - C07K 2317/70: characterized by effect upon binding to a cell or to an antigen - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - 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 ## Abstract Disclosed herein are methods and compositions for targeting a complex comprising a non-classical HLA-I and a neoantigen in cancer characterized by expression of CD94/NKG2A inhibitory receptor. Further disclosed herein are methods and compositions for combination cancer therapy. ## Claims ### Claim 1 A method of treating cancer characterized by expression of CD94/NKG2A inhibitory receptor in an individual in need thereof, comprising administering to the individual an antibody that selectively binds to a complex comprising an HLA-E and a neoantigen. ### Claim 2 (depends on 1) The method of claim 1, further comprising administering an additional anti-cancer agent. ### Claim 3 (depends on 1) The method of claim 1, further comprising assaying for expression of CD94/NKG2A inhibitory receptor in the individual. ### Claim 4 (depends on 1) The method of claim 1, wherein the cancer is characterized by the overexpression of the CD94/NKG2A inhibitory receptor. ### Claim 5 (depends on 1) The method of claim 1, wherein the antibody does not have a binding affinity to (i) the HLA-E alone; or (ii) the neoantigen alone. ### Claim 6 (depends on 1) The method of claim 1, wherein the neoantigen comprises, consists essentially of, or consists of a sequence VMAPRTLFL. ### Claim 7 (depends on 1) The method of claim 1, wherein the HLA-E is HLA-E*0101 or HLA-E*0103. ### Claim 8 (depends on 7) The method of claim 7, wherein the antibody selectively binds to the complex comprising: (a) the HLA-E*0101 and the neoantigen; (b) the HLA-E*0103 and the neoantigen; or (c) the HLA-E*0101 and the neoantigen, and the HLA-E*0103 and the neoantigen. ### Claim 9 (depends on 1) The method of claim 1, wherein the complex comprises the HLA-E and VMAPRTLFL. ### Claim 10 (depends on 1) The method of claim 1, wherein the antibody is a murine antibody, a chimeric antibody, a camelid antibody, a humanized antibody, or a human antibody. ### Claim 11 (depends on 1) The method of claim 1, wherein the antibody is a TCR-like antibody. ### Claim 12 (depends on 1) The method of claim 1, wherein the antibody is a single domain antibody. ### Claim 13 (depends on 12) The method of claim 12, wherein the single domain antibody is a camelid single domain antibody. ### Claim 14 (depends on 1) The method of claim 1, wherein the antibody is a multispecific antibody. ### Claim 15 (depends on 1) The method of claim 1, wherein the antibody is a multifunctional antibody. ### Claim 16 (depends on 1) The method of claim 1, wherein the selective binding of the antibody to the complex comprising the HLA-E and the neoantigen inhibits the binding of the complex to the CD94/NKG2A inhibitory receptor. ### Claim 17 (depends on 16) The method of claim 16, wherein the inhibition in binding of the complex to the CD94/NKG2A inhibitory receptor induces activation of natural killer (NK) cells. ### Claim 18 (depends on 16) The method of claim 16, wherein the inhibition in binding of the complex to the CD94/NKG2A inhibitory receptor induces activation of CD8+ T cells. ### Claim 19 (depends on 16) The method of claim 16, wherein the inhibition in binding of the complex to the CD94/NKG2A inhibitory receptor induces cell death of a cell expressing the HLA-E and the neoantigen. ### Claim 20 (depends on 19) The method of claim 19, wherein the cell is a cancer cell. ### Claim 21 (depends on 2) The method of claim 2, wherein the additional anti-cancer agent comprises CD20 inhibitor, HER-2 inhibitor, CD52 inhibitor, EGFR inhibitor, VEGF inhibitor, CCR4 inhibitor, PD-L1 inhibitor, SLAMF7 inhibitor, CD38 inhibitor, GD2 inhibitor, PTK-7 inhibitor, P-cadherin inhibitor, MCSF inhibitor, IDO1 inhibitor, CCR2 inhibitor, CXCR4 inhibitor, PD-1 inhibitor, CTLA-4 inhibitor, OX40 agonist, 4-1BB agonist, androgen receptor inhibitor, tyrosine kinase inhibitor, PARP inhibitor, chimeric antigen receptor T cells (CAR-T cells), oncolytic virus, and any combination thereof. ### Claim 22 (depends on 2) The method of claim 2, wherein the additional anti-cancer agent comprises Rituximab, Trastuzumab, Alemutuzumab, Cetixumab, Bevacizumab, Panitumumab, Obinutuzumab, Mogamulizumab, Necitumumab, Atezolizumab, Elotuzumab, Daratumumab, Dinutuximab, and any combination thereof. ### Claim 23 (depends on 2) The method of claim 2, wherein the antibody and the additional anti-cancer agent are administered concurrently. ### Claim 24 (depends on 2) The method of claim 2, wherein the antibody and the additional anti-cancer agent are administered sequentially. ### Claim 25 (depends on 2) The method of claim 2, wherein the antibody is administered prior to the additional anti-cancer agent. ### Claim 26 (depends on 2) The method of claim 2, wherein the antibody is administered after the additional anti-cancer agent. ### Claim 27 (depends on 2) The method of claim 2, wherein the antibody and the additional anti-cancer agent are administered in a unified dosage form. ### Claim 28 (depends on 2) The method of claim 2, wherein the antibody and the additional anti-cancer agent are administered in a separate dosage form. ### Claim 29 (depends on 2) The method of claim 2, wherein the antibody and the additional anti-cancer agent are administered continuously for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, 15, 28, 30 or more days. ### Claim 30 (depends on 2) The method of claim 2, wherein the antibody and the additional anti-cancer agent are administered at predetermined time intervals for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, 15, 28, 30 or more days. ### Claim 31 (depends on 2) The method of claim 2, wherein the antibody and the additional anti-cancer agent are administered intermittently for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, 15, 28, 30 or more days. ### Claim 32 (depends on 2) The method of claim 2, wherein the antibody and the additional anti-cancer agent are administered in 1 dose, 2 doses, 3 doses, 4 doses, 5 doses, 6 doses or more. ### Claim 33 (depends on 2) The method of claim 2, wherein the antibody and the additional anti-cancer agent are administered at a therapeutically effective amount. ### Claim 34 (depends on 1) The method of claim 1, wherein the cancer is breast cancer, kidney cancer, lung cancer, ovarian cancer, or colorectal cancer. ### Claim 35 (depends on 1) The method of claim 1, wherein the cancer is a B-cell malignancy. ### Claim 36 A method of treating cancer in an individual in need thereof, comprising administering to the individual: (a) an antibody that selectively binds to a complex comprising a HLA-E and a neoantigen, and (b) an additional anti-cancer agent. ### Claim 37 (depends on 36) The method of claim 36, wherein the antibody does not have a binding affinity to (i) the HLA-E alone; or (ii) the neoantigen alone. ### Claim 38 (depends on 36) The method of claim 36, wherein the neoantigen comprises, consists essentially of, or consists of a sequence VMAPRTLFL. ### Claim 39 (depends on 36) The method of claim 36, wherein the HLA-E is HLA-E*0101 or HLA-E*0103. ### Claim 40 (depends on 39) The method of claim 39, wherein the antibody selectively binds to the complex comprising: (a) the HLA-E*0101 and the neoantigen; (b) the HLA-E*0103 and the neoantigen; or (c) the HLA-E*0101 and the neoantigen, and the HLA-E*0103 and the neoantigen. ### Claim 41 (depends on 36) The method of claim 36, wherein the complex comprises the HLA-E and VMAPRTLFL. ### Claim 42 (depends on 36) The method of claim 36, wherein the antibody is a murine antibody, a chimeric antibody, a camelid antibody, a humanized antibody, or a human antibody. ### Claim 43 (depends on 36) The method of claim 36, wherein the antibody is a TCR-like antibody. ### Claim 44 (depends on 36) The method of claim 36, wherein the antibody is a single domain antibody. ### Claim 45 (depends on 44) The method of claim 44, wherein the single domain antibody is a camelid single domain antibody. ### Claim 46 (depends on 36) The method of claim 36, wherein the antibody is a multispecific antibody. ### Claim 47 (depends on 36) The method of claim 36, wherein the antibody is a multifunctional antibody. ### Claim 48 (depends on 36) The method of claim 36, wherein the selective binding of the antibody to the complex comprising the HLA-E and the neoantigen inhibits the binding of the complex to a CD94/NKG2A inhibitory receptor. ### Claim 49 (depends on 48) The method of claim 48, wherein the inhibition in binding of the complex to the CD94/NKG2A inhibitory receptor induces activation of natural killer (NK) cells. ### Claim 50 (depends on 48) The method of claim 48, wherein the inhibition in binding of the complex to the CD94/NKG2A inhibitory receptor induces activation of CD8+ T cells. ### Claim 51 (depends on 48) The method of claim 48, wherein the inhibition in binding of the complex to the CD94/NKG2A inhibitory receptor induces cell death of a cell expressing the HLA-E and the neoantigen. ### Claim 52 (depends on 51) The method of claim 51, wherein the cell is a cancer cell. ### Claim 53 (depends on 36) The method of claim 36, wherein the additional anti-cancer agent comprises CD20 inhibitor, HER-2 inhibitor, CD52 inhibitor, EGFR inhibitor, VEGF inhibitor, CCR4 inhibitor, PD-L1 inhibitor, SLAMF7 inhibitor, CD38 inhibitor, GD2 inhibitor, PTK-7 inhibitor, P-cadherin inhibitor, MCSF inhibitor, IDO1 inhibitor, CCR2 inhibitor, CXCR4 inhibitor, PD-1 inhibitor, CTLA-4 inhibitor, OX40 agonist, 4-1BB agonist, androgen receptor inhibitor, tyrosine kinase inhibitor, PARP inhibitor, chimeric antigen receptor T cells (CAR-T cells), oncolytic virus, and any combination thereof. ### Claim 54 (depends on 36) The method of claim 36, wherein the additional anti-cancer agent comprises Rituximab, Trastuzumab, Alemutuzumab, Cetixumab, Bevacizumab, Panitumumab, Obinutuzumab, Mogamulizumab, Necitumumab, Atezolizumab, Elotuzumab, Daratumumab, Dinutuximab, and any combination thereof. ### Claim 55 (depends on 36) The method of claim 36, wherein the antibody and the additional anti-cancer agent are administered concurrently. ### Claim 56 (depends on 36) The method of claim 36, wherein the antibody and the additional anti-cancer agent are administered sequentially. ### Claim 57 (depends on 36) The method of claim 36, wherein the antibody is administered prior to the additional anti-cancer agent. ### Claim 58 (depends on 36) The method of claim 36, wherein the antibody is administered after the additional anti-cancer agent. ### Claim 59 (depends on 36) The method of claim 36, wherein the antibody and the additional anti-cancer agent are administered in a unified dosage form. ### Claim 60 (depends on 36) The method of claim 36, wherein the antibody and the additional anti-cancer agent are administered in a separate dosage form. ### Claim 61 (depends on 36) The method of claim 36, wherein the antibody and the additional anti-cancer agent are administered continuously for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, 15, 28, 30 or more days. ### Claim 62 (depends on 36) The method of claim 36, wherein the antibody and the additional anti-cancer agent are administered at predetermined time intervals for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, 15, 28, 30 or more days. ### Claim 63 (depends on 36) The method of claim 36, wherein the antibody and the additional anti-cancer agent are administered intermittently for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, 15, 28, 30 or more days. ### Claim 64 (depends on 36) The method of claim 36, wherein the antibody and the additional anti-cancer agent are administered in 1 dose, 2 doses, 3 doses, 4 doses, 5 doses, 6 doses or more. ### Claim 65 (depends on 36) The method of claim 36, wherein the antibody and the additional anti-cancer agent are administered at a therapeutically effective amount. ### Claim 66 (depends on 36) The method of claim 36, wherein the cancer is characterized by expression of the CD94/NKG2A inhibitory receptor. ### Claim 67 (depends on 36) The method of claim 36, wherein the cancer is characterized by overexpression of the CD94/NKG2A inhibitory receptor. ### Claim 68 (depends on 66) The method of claim 66, further comprising assaying for expression of the CD94/NKG2A inhibitory receptor in the individual. ### Claim 69 (depends on 36) The method of claim 36, wherein the cancer is breast cancer, kidney cancer, lung cancer, ovarian cancer, or colorectal cancer. ### Claim 70 (depends on 36) The method of claim 36, wherein the cancer is a B-cell malignancy. ### Claim 71 A method of inducing cell death of a cancer cell in a tumor microenvironment characterized by expression of CD94/NKG2A inhibitory receptor in an individual in need thereof, comprising administering to the individual an antibody that selectively binds to a complex comprising an HLA-E and a neoantigen, wherein the complex is expressed by the cancer cell. ### Claim 72 (depends on 71) The method of claim 71, further comprising administering an additional anti-cancer agent. ### Claim 73 (depends on 71) The method of claim 71, further comprising assaying for expression of the CD94/NKG2A inhibitory receptor in the individual. ### Claim 74 (depends on 71) The method of claim 71, wherein the tumor microenvironment is characterized by the overexpression of the CD94/NKG2A inhibitory receptor. ### Claim 75 (depends on 71) The method of claim 71, wherein the antibody does not have a binding affinity to (i) the HLA-E alone; or (ii) the neoantigen alone. ### Claim 76 (depends on 71) The method of claim 71, wherein the neoantigen comprises, consists essentially of, or consists of a sequence VMAPRTLFL. ### Claim 77 (depends on 71) The method of claim 71, wherein the HLA-E is HLA-E*0101 or HLA-E*0103. ### Claim 78 (depends on 77) The method of claim 77, wherein the antibody selectively binds to the complex comprising: (a) the HLA-E*0101 and the neoantigen; (b) the HLA-E*0103 and the neoantigen; or (c) the HLA-E*0101 and the neoantigen, and the HLA-E*0103 and the neoantigen. ### Claim 79 (depends on 71) The method of claim 71, wherein the complex comprises the HLA-E and VMAPRTLFL. ### Claim 80 (depends on 71) The method of claim 71, wherein the antibody is a murine antibody, a chimeric antibody, a camelid antibody, a humanized antibody, or a human antibody. ### Claim 81 (depends on 71) The method of claim 71, wherein the antibody is a TCR-like antibody. ### Claim 82 (depends on 71) The method of claim 71, wherein the antibody is a single domain antibody. ### Claim 83 (depends on 82) The method of claim 82, wherein the single domain antibody is a camelid single domain antibody. ### Claim 84 (depends on 71) The method of claim 71, wherein the antibody is a multispecific antibody. ### Claim 85 (depends on 71) The method of claim 71, wherein the antibody is a multifunctional antibody. ### Claim 86 (depends on 71) The method of claim 71, wherein the selective binding of the antibody to the complex comprising the HLA-E and the neoantigen inhibits the binding of the complex to the CD94/NKG2A inhibitory receptor. ### Claim 87 (depends on 86) The method of claim 86, wherein the inhibition in binding of the complex to the CD94/NKG2A inhibitory receptor induces activation of natural killer (NK) cells. ### Claim 88 (depends on 86) The method of claim 86, wherein the inhibition in binding of the complex to the CD94/NKG2A inhibitory receptor induces activation of CD8+ T cells. ### Claim 89 (depends on 72) The method of claim 72, wherein the additional anti-cancer agent comprises CD20 inhibitor, HER-2 inhibitor, CD52 inhibitor, EGFR inhibitor, VEGF inhibitor, CCR4 inhibitor, PD-L1 inhibitor, SLAMF7 inhibitor, CD38 inhibitor, GD2 inhibitor, PTK-7 inhibitor, P-cadherin inhibitor, MCSF inhibitor, IDO1 inhibitor, CCR2 inhibitor, CXCR4 inhibitor, PD-1 inhibitor, CTLA-4 inhibitor, OX40 agonist, 4-1BB agonist, androgen receptor inhibitor, tyrosine kinase inhibitor, PARP inhibitor, chimeric antigen receptor T cells (CAR-T cells), oncolytic virus, and any combination thereof. ### Claim 90 (depends on 72) The method of claim 72, wherein the additional anti-cancer agent comprises Rituximab, Trastuzumab, Alemutuzumab, Cetixumab, Bevacizumab, Panitumumab, Obinutuzumab, Mogamulizumab, Necitumumab, Atezolizumab, Elotuzumab, Daratumumab, Dinutuximab, and any combination thereof. ### Claim 91 (depends on 72) The method of claim 72, wherein the antibody and the additional anti-cancer agent are administered concurrently. ### Claim 92 (depends on 72) The method of claim 72, wherein the antibody and the additional anti-cancer agent are administered sequentially. ### Claim 93 (depends on 72) The method of claim 72, wherein the antibody is administered prior to the additional anti-cancer agent. ### Claim 94 (depends on 72) The method of claim 72, wherein the antibody is administered after the additional anti-cancer agent. ### Claim 95 (depends on 72) The method of claim 72, wherein the antibody and the additional anti-cancer agent are administered in a unified dosage form. ### Claim 96 (depends on 72) The method of claim 72, wherein the antibody and the additional anti-cancer agent are administered in a separate dosage form. ### Claim 97 (depends on 72) The method of claim 72, wherein the antibody and the additional anti-cancer agent are administered continuously for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, 15, 28, 30 or more days. ### Claim 98 (depends on 72) The method of claim 72, wherein the antibody and the additional anti-cancer agent are administered at predetermined time intervals for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, 15, 28, 30 or more days. ### Claim 99 (depends on 72) The method of claim 72, wherein the antibody and the additional anti-cancer agent are administered intermittently for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14, 15, 28, 30 or more days. ### Claim 100 (depends on 72) The method of claim 72, wherein the antibody and the additional anti-cancer agent are administered in 1 dose, 2 doses, 3 doses, 4 doses, 5 doses, 6 doses or more. ### Claim 101 (depends on 72) The method of claim 72, wherein the antibody and the additional anti-cancer agent are administered at a therapeutically effective amount. ### Claim 102 (depends on 71) The method of claim 71, wherein the cancer cell is a breast cancer cell, a kidney cancer cell, a lung cancer cell, an ovarian cancer cell, or a colorectal cancer cell. ### Claim 103 (depends on 71) The method of claim 71, wherein the cancer cell is a malignant B cell. ### Claim 104 A pharmaceutical composition comprising: (a) an antibody that selectively binds to a complex comprising a HLA-E and a neoantigen; (b) an additional anti-cancer agent; and (c) a pharmaceutically acceptable carrier or excipient. ### Claim 105 (depends on 104) The pharmaceutical composition of claim 104 for use in treating a cancer. ### Claim 106 (depends on 104) The pharmaceutical composition of claim 104 for use in treating a cancer characterized by expression of CD94/NKG2A inhibitory receptor. ### Claim 107 (depends on 104) The pharmaceutical composition of claim 104 for use in treating a cancer characterized by overexpression of CD94/NKG2A inhibitory receptor.