Monoclonal antibodies activating cd40 and uses thereof

Abstract

The present disclosure provides isolated monoclonal antibodies or an antigen-binding portion thereof that specifically bind to CD40 preferably human CD40 with high affinity, and that function as CD40 agonists. The disclosed invention also relates to antibodies that are chimeric, humanized, bispecific, derivatized, single chain antibodies or portions of fusion proteins. Nucleic acid molecules encoding the antibodies of the disclosed invention, hybridoma, and methods for expressing the antibodies of the disclosed invention are also provided. Pharmaceutical compositions comprising the antibodies of the disclosed invention are also provided. This disclosure also provides methods for regulating humoral and cellular immune responses, as well as methods for treating cancer using an anti-CD40 agonist antibody of the disclosed invention.

1 . A monoclonal antibody, or an antigen-binding portion thereof comprising:
 (a) a heavy chain CDR1 amino acid sequence, CDR2 amino acid sequence, and CDR3 amino acid sequence, respectively, of amino acid residues 26-33, 51-58, and 97-111 of SEQ ID NO:1; and   (b) a light chain CDR1 amino acid sequence, CDR2 amino acid sequence, and CDR3 amino acid sequence, respectively, of amino acid residues 27-38, 56-58, and 95-103 of SEQ ID NO:2, wherein said antibody or portion specifically binds to and activates human CD40.   
     
     
         2 . (canceled) 
     
     
         3 . The antibody or antigen-binding portion according to  claim 1  that is a Fab fragment, an F(ab′) 2  fragment, an Fv fragment, a single chain antibody, or a bispecific antibody. 
     
     
         4 . A pharmaceutical composition comprising the antibody or antigen-binding portion-according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         5 .- 6 . (canceled) 
     
     
         7 . The monoclonal antibody, or an antigen-binding portion thereof of  claim 1 , wherein the antibody stimulates an anti-tumor immune response. 
     
     
         8 . A monoclonal antibody or an antigen-binding portion thereof comprising: a heavy chain variable domain comprising SEQ ID NO:1 and a light chain variable domain comprising SEQ ID NO:2, wherein the antibody specifically binds to and activates human CD40. 
     
     
         9 . (canceled) 
     
     
         10 . The antibody or antigen-binding portion according to  claim 8  that is a Fab fragment, an F(ab′) 2  fragment, an Fv fragment, a single chain antibody, or a bispecific antibody. 
     
     
         11 .- 13 . (canceled) 
     
     
         14 . The antibody of  claim 8 , wherein the antibody stimulates an anti-tumor immune response. 
     
     
         15 .- 16 . (canceled) 
     
     
         17 . The antibody according to  claim 1 , that is an immunoglobulin G (IgG), an IgM, an IgE, an IgA or an IgD molecule, or is derived therefrom. 
     
     
         18 . The monoclonal antibody according to  claim 17 , wherein said antibody is a chimeric antibody or humanized antibody. 
     
     
         19 . (canceled) 
     
     
         20 . The antibody according to  claim 8 , that is an immunoglobulin G (IgG), an IgM, an IgE, an IgA or an IgD molecule, or is derived therefrom. 
     
     
         21 . (canceled) 
     
     
         22 . The monoclonal antibody according to  claim 20 , wherein said antibody is a chimeric antibody or humanized antibody. 
     
     
         23 .- 24 . (canceled)