Monoclonal Antibodies for Treatment of Cancer

• US 20100111975A1
• Filed: 03/14/2008
• Published: 05/06/2010
• Est. Priority Date: 03/14/2007
• Status: Active Grant

• Current Assignee: Astellas Pharma Incorporated, TRANSLATIONALE ONKOLOGIE AN DER UNIVERSITATSMEDIZIN DER JOHANNES GUTENBERG-UNIVERSITAT MAINZ GEMEINNUTZIGE GMBH
• Original Assignee: Ganymed Pharmaceuticals AG (Astellas Pharma Incorporated), Johannes Gutenberg-Universitã¤T Mainz
• Inventors: Sahin, Ugur, Koslowski, Michael, Tureci, Ozlem
• Granted Patent: US 8,354,104 B2
• Time in Patent Office: Days
• US Class Current: 424/172.100
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

The present invention provides antibodies useful as therapeutics for treating and/or preventing diseases associated with cells expressing GT468, including tumor-related diseases such as breast cancer, lung cancer, gastric cancer, ovarian cancer, and hepatocellular cancer.

Claims

1-35. -35. (canceled)

36. An antibody having the ability of binding to GT468 and mediating killing and/or inhibition of one or more activities of cells expressing GT468 and/or being characterized by association of GT468 with the cell surface of said cells.

37. The antibody of claim 36 wherein said one or more activities is selected from the group consisting essentially of cell motility, cell migration, invasion of cells and cell proliferation.

38. The antibody of claim 36 wherein said one or more activities is cell proliferation.

39. The antibody of claim 36 wherein said killing and/or inhibition of one or more activities of cells is induced by binding of said antibody to GT468 expressed by said cells and/or associated with the surface of said cells.

40. The antibody of claim 36 wherein said killing and/or inhibition of one or more activities of cells is induced by binding of said antibody to an extracellular domain of GT468 expressed by said cells and/or associated with the surface of said cells.

41. The antibody of claim 36 wherein said killing and/or inhibition of one or more activities is not induced by binding of said antibody to non-cancerous GT468 expressing cells.

42. The antibody of claim 36 wherein said cells expressing GT468 and/or being characterized by association of GT468 with the cell surface of said cells are cancer cells.

43. The antibody of claim 42 wherein the cancer cells are selected from the group consisting essentially of tumorigenic breast, lung, gastric, ovarian and hepatocellular cancer cells.

44. The antibody of claim 36 which mediates said killing of cells by inducing complement dependent cytotoxicity (CDC) mediated lysis, antibody dependent cellular cytotoxicity (ADCC) mediated lysis, apoptosis, homotypic adhesion, and/or phagocytosis.

45. The antibody of claim 36 which mediates said killing of cells by inducing CDC mediated lysis and/or ADCC mediated lysis.

46. The antibody of claim 36 which does not induce CDC mediated lysis of said cells.

47. The antibody of claim 44 wherein said ADCC mediated lysis takes place in the presence of effector cells selected from the group consisting of monocytes, mononuclear cells, NK cells and PMNs.

48. The antibody of claim 44 wherein said phagocytosis is by macrophages.

49. The antibody of claim 36 which is a monoclonal, chimeric, human or humanized antibody, or a fragment of an antibody.

50. The antibody of claim 36 selected from the group consisting essentially of an IgG1, an IgG2, an IgG2a, an IgG2b, an IgG3, an IgG4, an IgM, an IgA1, an IgA2, a secretory IgA, an IgD, and an IgE antibody.

51. The antibody of claim 36 wherein GT468 has an amino acid sequence according to SEQ ID NO:

2.

52. The antibody of claim 36 wherein the antibody binds specifically to GT468.

53. The antibody of claim 36 which binds to native epitopes of GT468 present on the surface of living cells.

54. The antibody of claim 36 which is specific for cancer cells or breast cancer cells.

55. The antibody of claim 36 wherein said GT468 is expressed on the surface of said cells.

56. The antibody of claim 36 which is obtainable by a method comprising a step of immunizing an animal with a protein or peptide having an amino acid sequence selected from the group consisting essentially of SEQ ID NO:

2-10 and SEQ ID NO;

35-79, an immunogenic fragment, a nucleic acid, a host cell expressing said protein, a peptide, an immunogenic fragment, or derivative thereof.

58. A hybridoma capable of producing the antibody of claim 36.

60. The antibody of claim 36 wherein said antibody is conjugated to a therapeutic agent.

61. The antibody of claim 60 wherein the therapeutic agent is a toxin, a radioisotope, a drug or a cytotoxic agent.

62. A pharmaceutical composition comprising the antibody of claim 36 and a pharmaceutically acceptable carrier.

63. A method of inhibiting growth, killing, or inhibiting metastatic spread of a cell expressing GT468 and/or being characterized by association of GT468 with the cell surface of said cell, comprising contacting the cell with an effective amount of the antibody of claim 36.

64. A method of treating or preventing a disease or disorder involving cells expressing GT468 and/or being characterized by association of GT468 with the cell surface of said cells, comprising administering to a subject the antibody of claim 36 and a pharmaceutically acceptable carrier.

65. The method of claim 64 wherein the disease or disorder is a tumor-related disease.

66. The method of claim 65 wherein the tumor-related disease is selected from the group consisting of breast cancer, lung cancer, gastric cancer, ovarian cancer and hepatocellular cancer.

67. The method of claim 63 or 64, wherein said GT468 has an amino acid sequence according to SEQ ID NO:

2.

68. The method of claim 63 or 64 wherein said GT468 is expressed on the surface of said cell.

57. An antibody produced by a clone deposited under accession no. DSM ACC2822 (4E9-1H9), DSM ACC2826 (9B6-2A9), DSM ACC2824 (59D6-2F2), DSM ACC2825 (61C11-2B5), DSM ACC2823 (78H11-1H6), DSM ACC2895 (22-1A-1), DSM ACC2893 (22-2A-1), DSM ACC2896 (22-9B-1), DSM ACC2897 (23-33A-1), DSM ACC2891 (23-19A-1), DSM ACC2894 (F11#33F7D12), DSM ACC2892 (4A12 2D4 1A10), or DSM ACC2898 (4E9 1D12 2D4).

59. A hybridoma deposited under accession no. DSM ACC2822 (4E9-1H9), DSM ACC2826 (9B6-2A9), DSM ACC2824 (59D6-2F2), DSM ACC2825 (61C11-2B5), DSM ACC2823 (78H11-1H6), DSM ACC2895 (22-1A-1), DSM ACC2893 (22-2A-1), DSM ACC2896 (22-9B-1), DSM ACC2897 (23-33A-1), DSM ACC2891 (23-19A-1), DSM ACC2894 (F11#33F7D12), DSM ACC2892 (4A12 2D4 1A10), or DSM ACC2898 (4E9 1D12 2D4).