Anti-cd40 antibodies and methods of use

Abstract

The present invention provides high affinity anti-CD40 monoclonal antibodies and related compositions, which may be used in any of a variety of therapeutic methods for the treatment of cancer and other diseases.

1 - 23 . (canceled) 
     
     
         24 . An isolated antibody, or antigen-binding fragment thereof, that binds to CD40, wherein the isolated antibody, or an antigen-binding fragment thereof, comprises (i) a heavy chain variable region comprising the VHCDR1 region set forth in SEQ ID NO:3, the VHCDR2 region set forth in SEQ ID NO:4, and the VHCDR3 region set forth SEQ ID NO:5; and (ii) a light chain variable region comprising the VLCDR1 region set forth in SEQ ID NO:6, the VLCDR2 region set forth in SEQ ID NO:7, and the VLCDR3 region set forth in SEQ ID NO: 8; and comprising an Fc region modified by a S267E mutation;
 or a variant of said antibody, or an antigen-binding fragment thereof, comprising heavy and light chain variable regions identical to the heavy and light chain variable regions of (i) and (ii) except for up to 8 amino acid substitutions in said CDR regions.   
     
     
         25 . The isolated antibody, or antigen-binding fragment thereof, of  claim 24 , wherein the antibody is humanized. 
     
     
         26 . The isolated antibody, or antigen-binding fragment thereof, of  claim 24 , wherein the antibody is selected from the group consisting of a single chain antibody and a univalent antibody lacking a hinge region. 
     
     
         27 . The isolated antibody, or antigen-binding fragment thereof, of  claim 24 , wherein the antibody is a whole antibody. 
     
     
         28 . The isolated antibody, or antigen-binding fragment thereof, of  claim 24  comprising a human IgG constant domain. 
     
     
         29 . The isolated antibody, or antigen-binding fragment thereof, of  claim 28 , wherein the IgG constant domain comprises an IgG1 CH1 domain. 
     
     
         30 . The isolated antibody, or antigen-binding fragment thereof, of  claim 28 , wherein the IgG constant domain comprises an IgG1 Fc region. 
     
     
         31 . The isolated antibody, or antigen-binding fragment thereof, of  claim 24 , which competes with an antibody comprising the VH region set forth in SEQ ID NO: 1 and the VL region set forth in SEQ ID NO:2 for binding to CD40. 
     
     
         32 . An isolated polynucleotide encoding the isolated antibody, or antigen-binding fragment thereof, according to  claim 24 . 
     
     
         33 . An expression vector comprising the isolated polynucleotide of  claim 32 . 
     
     
         34 . An isolated host cell comprising the vector of  claim 33 . 
     
     
         35 . A composition comprising a physiologically acceptable carrier and a therapeutically effective amount of the isolated antibody, or antigen-binding fragment thereof, according to  claim 24 . 
     
     
         36 . A method of treating or ameliorating the symptoms of cancer in a patient, comprising administering to the patient the composition of  claim 35 , thereby treating or ameliorating the symptoms of the cancer. 
     
     
         37 . The method of  claim 36 , wherein the cancer is selected from the group consisting of non-Hodgkin's lymphomas, Hodgkin's lymphoma, chronic lymphocytic leukemias, hairy cell leukemias, acute lymphoblastic leukemias, multiple myeloma, carcinomas of the bladder, kidney ovary, cervix, breast, lung, nasopharynx, malignant melanoma and rituximab resistant NHL and leukemias. 
     
     
         38 . A method for ameliorating symptoms of an autoimmune disease in a patient comprising administering to the patient the composition of  claim 35 , thereby ameliorating the symptoms of an autoimmune disease. 
     
     
         39 . A method for ameliorating symptoms of inflammatory disease in a patient comprising administering to the patient the composition of  claim 35 , thereby ameliorating the symptoms of inflammatory disease.