Humanized Anti-CXCR5 Antibodies, Derivatives Thereof And Their Use
The present invention relates to humanized antibodies that specifically bind to CXCR5 and can, for example, inhibit CXCR5 function. The invention also includes uses of the antibodies to treat or prevent CXCR5 related diseases or disorders.
1 - 25 . (canceled)
26 . An isolated antibody or fragment thereof that specifically binds to the extracellular domain of human CXCR5, wherein the antibody or fragment thereof comprises:
(a) a light chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 11, and a heavy chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 12;
(b) a light chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 13, SEQ ID NO: 14, or SEQ ID NO: 15, and a heavy chain variable domain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 16;
(c) a variable light chain (V L ) comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 17, SEQ ID NO: 19, or SEQ ID NO: 21, and a variable heavy chain (V H ) comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 23;
(d) a variable light chain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 30, SEQ ID NO: 31, or SEQ ID NO: 32, and a variable heavy chain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 33 or SEQ ID NO: 34;
(e) a variable light chain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 35, and a variable heavy chain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 37;
(f) a variable light chain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 39, SEQ ID NO: 41, or SEQ ID NO: 43, and a variable heavy chain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 45 or SEQ ID NO: 47; or
(g) a variable light chain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 55, and a variable heavy chain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 56 or SEQ ID NO: 57.
27 . An isolated antibody or fragment thereof that specifically binds to the extracellular domain of human CXCR5, wherein the antibody or fragment thereof comprises a variable light chain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 32, and a variable heavy chain comprising an amino sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 33.
28 . The antibody or fragment thereof of either claim 26 or 27 , wherein the antibody or fragment thereof further comprises one or more constant region domains.
29 . The antibody or fragment thereof of either claim 26 or 27 , wherein the antibody or fragment thereof further comprises a C H1 , C H2 , C H3 , or combinations thereof.
30 . The antibody or fragment thereof of claim 28 , wherein the one or more constant region domains are from an IgG antibody.
31 . The antibody or fragment thereof of claim 30 , wherein the IgG antibody is an IgG4 antibody.
32 . The antibody or fragment thereof of either claim 26 or 27 , wherein the antibody or fragment thereof is a single chain Fv antibody.
33 . A pharmaceutical composition comprising a therapeutically effective amount of the antibody or fragment thereof of either claim 26 or 27 and a pharmaceutically acceptable carrier.
34 . An isolated nucleic acid molecule encoding the antibody or fragment thereof of either claim 26 or 27 .
35 . A vector comprising the nucleic acid molecule of claim 34 .
36 . An isolated host cell comprising the vector of claim 35 .
37 . A method of treating a patient having a CXCR5 disease or condition, comprising administering to the patient a therapeutically effective amount of the antibody or fragment thereof of either claim 26 or 27 .
38 . The method of claim 37 , wherein the CXCR5 disease or condition is pancreatic cancer, colon cancer, bladder cancer, T cell leukemia, B cell leukemia, lupus, Sjoren's Syndrome, myasthenia gravis, multiple sclerosis, ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, a chronic inflammatory disease, or a graft undergoing rejection.
39 . A method of treating a patient having a disorder comprising CXCR5 positive cells, comprising administering to the patient a therapeutically effective amount of the antibody or fragment thereof of either claim 26 or 27 .
40 . The method of claim 39 , wherein the disorder comprising CXCR5 positive cells is pancreatic cancer, colon cancer, bladder cancer, T cell leukemia, B cell leukemia, lupus, Sjoren's Syndrome, myasthenia gravis, multiple sclerosis, ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, a chronic inflammatory disease, or a graft undergoing rejection.
41 . The method of claim 39 , wherein at least one of the CXCR5 positive cells is a B cell.
42 . The method of claim 39 , wherein at least one of the CXCR5 positive cells is activated by CXCL13.
43 . The method of claim 39 , wherein at least one of the CXCR5 positive cells is a T cell.