Modulation of immune response using btla agonist antibodies

Abstract

The present invention relates to the seminal discovery that BTLA agonist antibodies modulate the immune system. Specifically, the present invention provides antibodies which bind BTLA in the activated state enhancing BTLA signaling. The present invention further provides methods of treating immune and inflammatory diseases and disorders with a BTLA agonist antibody.

1 - 21 . (canceled) 
     
     
         22 . An isolated BTLA agonist antibody, wherein the antibody binds to activated BTLA, does not block HVEM binding to BTLA, and comprises all three complementarity-determining regions (CDRs) of SEQ ID NO: 1 and all three CDRs of SEQ ID NO: 2. 
     
     
         23 . (canceled) 
     
     
         24 . The antibody of  claim 22 , wherein BTLA signaling is enhanced. 
     
     
         25 . The antibody of  claim 22 , wherein the binding of the antibody to BTLA results in phosphorylation of the cytoplasmic domain of BTLA. 
     
     
         26 . The antibody of  claim 22 , wherein the binding of the antibody to BTLA recruits SHP1. 
     
     
         27 . The antibody of  claim 22 , wherein the antibody is 6F4. 
     
     
         28 . A pharmaceutical composition comprising the isolated BTLA agonist antibody of  claim 22 , and a pharmaceutically acceptable carrier. 
     
     
         29 - 32 . (canceled) 
     
     
         33 . The pharmaceutical composition of  claim 28 , wherein the antibody is monoclonal, chimeric, human, or humanized or a binding fragment thereof. 
     
     
         34 . The pharmaceutical composition of  claim 33 , wherein the antibody is monoclonal or chimeric, or a binding fragment thereof. 
     
     
         35 . The pharmaceutical composition of  claim 34 , wherein the antibody is monoclonal. 
     
     
         36 . The pharmaceutical composition of  claim 34 , wherein the antibody is chimeric. 
     
     
         37 . The pharmaceutical composition of  claim 28 , wherein the binding of the antibody to BTLA recruits SHP2. 
     
     
         38 . The pharmaceutical composition of  claim 28 , wherein the antibody was produced from one or more rat(s). 
     
     
         39 . The pharmaceutical composition of  claim 37 , wherein the one or more rat(s) was(were) immunized with huBTLA:huIgG recombinant fusion protein. 
     
     
         40 . The antibody of  claim 22 , wherein the antibody is monoclonal, chimeric, human, or humanized or a binding fragment thereof. 
     
     
         41 . The antibody of  claim 39 , wherein the antibody is monoclonal or chimeric, or a binding fragment thereof. 
     
     
         42 . The antibody of  claim 41 , wherein the antibody is monoclonal. 
     
     
         43 . The antibody of  claim 41 , wherein the antibody is chimeric. 
     
     
         44 . The antibody of  claim 22 , wherein the binding of the antibody to BTLA recruits SHP2. 
     
     
         45 . The antibody of  claim 22 , wherein the antibody was produced from one or more rat(s). 
     
     
         46 . The antibody of  claim 45 , wherein the one or more rat(s) was(were) immunized with huBTLA:huIgG recombinant fusion protein.