Humanized anti-cd40 antibodies conjugated to therapeutic agents

Abstract

Provided are humanized anti-CD40 antibodies and antigen-binding fragments and methods for treating disease characterized by expression of CD40 antigen.

1 - 49 . (canceled) 
     
     
         50 . An isolated antibody or antigen-binding fragment that specifically binds to human CD40, comprising a humanized heavy chain variable domain and a humanized light chain variable domain, wherein the heavy chain variable domain and the light chain variable domain comprise the amino acid sequences of SEQ ID NO:10 and SEQ ID NO:16, respectively, and wherein the antibody or antigen-binding fragment is conjugated to chemotherapeutic agent. 
     
     
         51 . The antibody or antigen-binding fragment of  claim 50 , wherein the chemotherapeutic agent is an auristatin. 
     
     
         52 . The antibody or antigen-binding fragment of  claim 51 , wherein the auristatin is MMAE or MMAF. 
     
     
         53 . The antibody or antigen-binding fragment of  claim 50 , further comprising a human IgG constant region. 
     
     
         54 . The antibody or antigen-binding fragment of  claim 53 , wherein the isotype of the IgG constant region is IgG1, IgG2, IgG3, or IgG4. 
     
     
         55 . The antibody or antigen-binding fragment of  claim 54 , wherein the isotype of the IgG constant region is IgG1. 
     
     
         56 . The antibody or antigen-binding fragment of  claim 50 , further comprising a light chain constant domain. 
     
     
         57 . The antibody or antigen-binding fragment of  claim 56 , wherein the light chain constant domain is a kappa constant domain. 
     
     
         58 . The antibody of  claim 50 , wherein the antibody further comprises a human immunoglobulin constant region. 
     
     
         59 . The antibody of  claim 58 , comprising the heavy chain and the light chain amino acid sequences set forth in SEQ ID NO:19 and SEQ ID NO:22, respectively. 
     
     
         60 . The antibody or antigen-binding fragment of  claim 50 , which is an antigen-binding antibody fragment. 
     
     
         61 . The antigen-binding fragment of  claim 60 , wherein the antibody fragment is a Fab, a Fab′, a F(ab) 2 , a Fv fragment, a diabody, a single-chain antibody, an scFv fragment or an scFv-Fc. 
     
     
         62 . A method for treating a subject having a CD40-expressing cancer, comprising administering to the subject the antibody or antigen-binding fragment of  claim 50 . 
     
     
         63 . The method of  claim 62 , wherein the cells of the CD40-expressing cancer are B lymphoblastoid cells, pancreatic cells, lung cells, breast cells, ovarian cells, colon cells, prostate cells, skin cells, head and neck cells, bladder cells, bone cells or kidney cells. 
     
     
         64 . The method of  claim 62 , wherein the CD40-expressing cancer is chronic lymphocytic leukemia, Burkitt's lymphoma, multiple myeloma, a T cell lymphoma, Non-Hodgkin's Lymphoma, Hodgkin's Disease, Waldenstrom's macroglobulinemia or Kaposi's sarcoma. 
     
     
         65 . A pharmaceutical composition comprising: (i) the antibody or antigen-binding fragment of  claim 50 ; and (ii) a pharmaceutically acceptable excipient.