4-1bb binding molecules

Abstract

The present disclosure provides isolated binding molecules that bind to human 4-1BB, nucleic acid molecules encoding an amino acid sequence of the binding molecules, vectors comprising the nucleic acid molecules, host cells containing the vectors, methods of making the binding molecules, pharmaceutical compositions containing the binding molecules, and methods of using the binding molecules or compositions.

1 - 7 . (canceled) 
     
     
         8 . An isolated antibody or an antigen-binding portion thereof wherein said antibody or antigen-binding portion binds human 4-1BB extracellular domain, and wherein said binding is abrogated by one or more mutations of SEQ ID NO: 68 selected from K115Q, C121R, R134Q, R154S, or V156A. 
     
     
         9 . The antibody or antigen-binding portion thereof according to  claim 8  wherein the one or more mutations of SEQ ID NO: 68 comprise K115Q, C121R, R134Q, R154S, and V156A. 
     
     
         10 . A pharmaceutical composition comprising an antibody or antigen-binding portion thereof according to  claim 8  and a pharmaceutically acceptable carrier. 
     
     
         11 . An isolated antibody, wherein said antibody comprises a V H  and a V L  region wherein the V H  region amino acid sequence comprises the amino acid sequence set forth in SEQ ID NO: 43 and the V L  region amino acid sequence comprises the amino acid sequence set forth in SEQ ID NO: 45, wherein the antibody isotype is IgG 1. 
     
     
         12 . The antibody according to  claim 11  wherein said antibody comprises the human IgG 1 constant domain amino acid sequence comprising the amino acid sequence set forth in SEQ ID NO: 69, with the proviso that the C-terminal lysine residue of SEQ ID NO: 69 is optionally absent. 
     
     
         13 . A pharmaceutical composition comprising an antibody according to  claim 11  and a pharmaceutically acceptable carrier. 
     
     
         14 . A method for reducing tumor growth in a subject in need thereof, comprising administering to the subject an effective amount of an antibody or antigen-binding portion thereof according to  claim 8 . 
     
     
         15 . A method of treating cancer in a mammal, which comprises administering to the mammal in need of treatment a therapeutically effective amount of an antibody or antigen-binding portion thereof according to  claim 8 . 
     
     
         16 . The method of  claim 15  wherein said cancer is selected from the group consisting of colorectal cancer, non-Hodgkin's lymphoma, prostate cancer, or melanoma. 
     
     
         17 . The method of  claim 15  further comprising administering an immunotherapeutic agent. 
     
     
         18 . The method of  claim 17  wherein said immunotherapeutic agent is rituximab. 
     
     
         19 . A method for reducing tumor growth in a subject in need thereof, comprising administering to the subject an effective amount of an antibody according to  claim 11 . 
     
     
         20 . A method of treating cancer in a mammal, which comprises administering to the mammal in need of treatment a therapeutically effective amount of an antibody according to  claim 11 . 
     
     
         21 . The method of  claim 20  wherein said cancer is selected from the group consisting of colorectal cancer, non-Hodgkin's lymphoma, prostate cancer, or melanoma. 
     
     
         22 . The method of  claim 20  further comprising administering an immunotherapeutic agent. 
     
     
         23 . The method of  claim 22  wherein said immunotherapeutic agent is rituximab.