Abstract: The present invention relates to humanized monoclonal antibodies LB-00503 and LB-00506, which are specific for human 4-1BB molecules, have high binding affinities and can bind efficiently with activated T cells expressing the 4-1BB molecule, as well as pharmaceutical compositions. Particularly, the present invention provides said humanized antibody LB-00503, which is modified from the humanized antibody Hz4B4-2 and substitutes the 61st amino acid, serine by asparagine in the amino acid residues of 59th˜61st and said humanized antibody LB-00506, which enhances the antibody binding affinity of said humanized antibody LB-00503 in which 2 amino acid residues of the right border in the antibody binding site CDR2 of the heavy chain variable region are substituted from glutamine (Q)—glycine (G) to lysine (K)—serine (S).

Abstract: The present invention is directed to humanized antibodies that specifically bind the protein 4-1BB. The antibodies can be made by grafting of the complementarity determining regions (CDR's) of mouse monoclonal antibody to human 4-1BB to the remaining portions of a human antibody and by making further amino acid replacements. In addition, a pharmaceutical composition that includes the humanized antibody can be made and can be used to treat autoimmune diseases to suppress an immune response. The humanized antibody of the invention has high affinity for human 4-1BB, and exhibits sequence similarity to human antibody. As a result, the pharmaceutical composition of the present invention can be used to treat autoimmune disease and act as an immunosuppressant in humans without much side-effect.