Human monoclonal antibodies against cd25

Abstract

Isolated human monoclonal antibodies which bind to and inhibit human CD25, and related antibody-based compositions and molecules, are disclosed. The human antibodies can be produced by a hybridoma, a transfectoma or in a nonhuman transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, nonhuman transgenic animals, hybridomas and transfectomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

1 - 27 . (canceled) 
     
     
         28 . A method of treating a solid malignancy, the method comprising administering an antibody that binds to human CD25 in an amount effective to treat the malignancy, wherein the antibody is selected from the group consisting of:
 (a) an antibody wherein at least one variable region is selected from the group consisting of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, and 16;   (b) an antibody comprising heavy and light chain variable region sequences set forth in SEQ ID NOs: 6 and 8, respectively;   (c) an antibody comprising heavy and light chain variable region sequences set forth in SEQ ID NOs: 14 and 16, respectively;   (d) an antibody comprising heavy and light chain variable region sequences set forth in SEQ ID NOs: 2 and 4, respectively;   (e) an antibody comprising heavy and light chain variable region sequences set forth in SEQ ID NOs: 10 and 12, respectively;   (f) an antibody comprising heavy or light chain CDR sequences set forth in SEQ ID NOs: 35, 36, 37 and SEQ ID NOs: 38, 39, 40, respectively;   (g) an antibody comprising heavy and light chain CDR sequences set forth in SEQ ID NOs: 17, 18, 19 and SEQ ID NOs: 20, 21, 22, respectively;   (h) an antibody comprising heavy and light chain CDR sequences set forth in SEQ ID NOs: 23, 24, 25 and SEQ ID NOs: 26, 27, 28, respectively;   (i) an antibody comprising heavy and light chain CDR sequences set forth in SEQ ID NOs: 29, 30, 31 and SEQ ID NOs: 32, 33, 34, respectively;   (j) an antibody which binds to an epitope on human CD25 defined by antibody (b), (c), (d) or (e); and   (k) an antibody having the binding characteristics of antibody (b), (c), (d) or (e).   
     
     
         29 . The method of  claim 28 , wherein the malignancy is a selected from the group consisting of gastric cancer, esophageal cancer, malignant melanoma, colorectal cancer, pancreas cancer, breast cancer, small cell lung cancer, non-small cell lung cancer, cervical cancer, ovarian cancer, and renal cell carcinoma. 
     
     
         30 . The method of  claim 28 , further comprising separately administering another therapeutic agent and/or therapy to the subject. 
     
     
         31 . The method of  claim 30 , wherein the therapeutic agent is an immunosuppressant selected from the group consisting of cyclosporine, azathioprine, mycophenolic acid, mycophenolate mofetil, corticosteroids, prednisone, methotrexate, gold salts, sulfasalazine, antimalarials, brequinar, leflunomide, mizoribine, 15-deoxyspergualine, 6-mercaptopurine, cyclophosphamide, rapamycin, tacrolimus, OKT3, and anti-thymocyte globulin. 
     
     
         32 . The method of  claim 30 , wherein the therapeutic agent is an anti-inflammatory agent selected from the group consisting of a steroidal drug, a nonsteroidal anti-inflammatory drug, and a disease modifying anti-rheumatic drug. 
     
     
         33 . The method of  claim 30 , wherein the therapeutic agent is an agent or therapy for treating an inflammatory or hyperproliferative skin disorder selected from the group consisting of coal tar, A vitamin, anthralin, calcipotrien, tarazotene, corticosteroids, methotrexate, retinoids, cyclosporine, etanercept, alefacept, efaluzimab, 6-thioguanine, mycophenolate mofetil, tacrolimus, hydroxyurea, and phototherapy. 
     
     
         34 . The method of  claim 30 , wherein the therapeutic agent is selected from the group consisting of doxorubicin, cisplatin, bleomycin, carmustine, chlorambucil, and cyclophosphamide. 
     
     
         35 . The method of  claim 28 , wherein the antibody is an IgG1 or IgG4 antibody. 
     
     
         36 . The method of  claim 28 , wherein the antibody is linked to a cytotoxic agent, a radioisotope, or a drug. 
     
     
         37 . The method of  claim 28 , wherein the antibody is a human, monoclonal IgG1 antibody, a bispecific antibody, or a multispecific antibody. 
     
     
         38 . The method of  claim 37 , wherein the bispecific or the multispecific antibody further comprises a binding specificity for CD3, CD4, IL-15R, membrane bound or receptor bound TNF-α, or receptor bound IL-15. 
     
     
         39 . An anti-idiotypic antibody binding to an antibody as defined in  claim 28 . 
     
     
         40 . A nucleic acid encoding an antibody that binds to human CD25, wherein the antibody is selected from the group consisting of:
 (a) an antibody comprising heavy and light chain variable region sequences set forth in SEQ ID NOs: 6 and 8, respectively;   (b) an antibody comprising heavy and light chain variable region sequences set forth in SEQ ID NOs: 14 and 16, respectively;   (c) an antibody comprising heavy and light chain variable region sequences set forth in SEQ ID NOs: 2 and 4, respectively;   (d) an antibody comprising heavy and light chain variable region sequences set forth in SEQ ID NOs: 10 and 12, respectively;   (e) an antibody comprising heavy and light chain CDR sequences set forth in SEQ ID NOs: 35, 36, 37 and SEQ ID NOs: 38, 39, 40, respectively;   (f) an antibody comprising heavy and light chain CDR sequences set forth in SEQ ID NOs: 17, 18, 19 and SEQ ID NOs: 20, 21, 22, respectively;   (g) an antibody comprising heavy and light chain CDR sequences set forth in SEQ ID NOs: 23, 24, 25 and SEQ ID NOs: 26, 27, 28, respectively; and   (h) an antibody comprising heavy and light chain CDR sequences set forth in SEQ ID NOs: 29, 30, 31 and SEQ ID NOs: 32, 33, 34, respectively.   
     
     
         41 . An expression vector comprising the nucleic acid of  claim 40 . 
     
     
         42 . A host cell comprising the expression vector of  claim 41 . 
     
     
         43 . A combination of isolated nucleic acids encoding the heavy chain and light chain of an antibody which binds to human CD25, wherein the antibody is selected from the group consisting of:
 (a) an antibody comprising heavy and light chain variable region sequences set forth in SEQ ID NOs: 6 and 8, respectively;   (b) an antibody comprising heavy and light chain variable region sequences set forth in SEQ ID NOs: 14 and 16, respectively;   (c) an antibody comprising heavy and light chain variable region sequences set forth in SEQ ID NOs: 2 and 4, respectively;   (d) an antibody comprising heavy and light chain variable region sequences set forth in SEQ ID NOs: 10 and 12, respectively;   (e) an antibody comprising heavy and light chain CDR sequences set forth in SEQ ID NOs: 35, 36, 37 and SEQ ID NOs: 38, 39, 40, respectively;   (f) an antibody comprising heavy and light chain CDR sequences set forth in SEQ ID NOs: 17, 18, 19 and SEQ ID NOs: 20, 21, 22, respectively;   (g) an antibody comprising heavy and light chain CDR sequences set forth in SEQ ID NOs: 23, 24, 25 and SEQ ID NOs: 26, 27, 28, respectively; and   (h) an antibody comprising heavy and light chain CDR sequences set forth in SEQ ID NOs: 29, 30, 31 and SEQ ID NOs: 32, 33, 34, respectively.