Antibodies that bind human cannabinoid 1 (cb1) receptor

Abstract

The present invention relates to novel antibodies and fragments thereof that binds cannabinoid 1 (CB1) receptor. The antibodies and fragments thereof as disclosed herein include humanized antibodies that bind CB1 receptor. The invention also includes uses of the antibodies for treating a disease or disorder responsive to antagonism or agonism of the CB1 receptor.

1 - 21 . (canceled) 
     
     
         22 . An isolated antibody or antigen binding fragment thereof that binds to cannabinoid 1 (CB1) receptor, wherein the antibody or antigen binding fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 according to SEQ ID NOs: 352, 353, and 354, respectively, and a light chain CDR1, CDR2, and CDR3 according to one of the following:
 (a) SEQ ID NOs: 833, 694, and 836, respectively;   (b) SEQ ID NOs: 833, 835, and 836, respectively;   (c) SEQ ID NOs: 833, 694, and 357, respectively; and   (d) SEQ ID NOs: 833, 834, and 779, respectively, and   
       wherein the antibody or antigen binding fragment thereof comprises at least one of the following:
 a light chain variable region comprising an amino acid sequence that is, excluding the CDRs, at least 95% identical to SEQ ID NO: 337, and 
 a heavy chain variable region comprising an amino acid sequence that is, excluding the CDRs, at least 95% identical to SEQ ID NO: 339, 340 or 341. 
 
     
     
         23 . The isolated antibody or antigen binding fragment of  claim 22 , wherein the light chain CDR1, CDR2, and CDR3 according to SEQ ID NOs: 833, 694, and 836, respectively. 
     
     
         24 . The isolated antibody or antigen binding fragment of  claim 23 , wherein the antibody or antigen binding fragment thereof comprises a light chain, excluding the CDRs, at least 95% identical to SEQ ID NO: 829. 
     
     
         25 . The isolated antibody or antigen binding fragment of  claim 24 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain, excluding the CDRs, at least 95% identical to SEQ ID NO: 437. 
     
     
         26 . The isolated antibody or antigen binding fragment of  claim 22 , wherein the light chain CDR1, CDR2, and CDR3 are according to SEQ ID NOs: 833, 835, and 836, respectively. 
     
     
         27 . The isolated antibody or antigen binding fragment of  claim 26 , wherein the antibody or antigen binding fragment thereof comprises a light chain at least 95% identical to SEQ ID NO: 830. 
     
     
         28 . The isolated antibody or antigen binding fragment of  claim 27 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain, excluding the CDRs, at least 95% identical to SEQ ID NO: 437. 
     
     
         29 . The isolated antibody or antigen binding fragment of  claim 22 , wherein the light chain CDR1, CDR2, and CDR3 are according to SEQ ID NOs: 833, 694, and 357, respectively. 
     
     
         30 . The isolated antibody or antigen binding fragment of  claim 29 , wherein the antibody or antigen binding fragment thereof comprises a light chain, excluding the CDRs, at least 95% identical to SEQ ID NO: 831. 
     
     
         31 . The isolated antibody or antigen binding fragment of  claim 30 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain, excluding the CDRs, at least 95% identical to SEQ ID NO: 437. 
     
     
         32 . The isolated antibody or antigen binding fragment of  claim 22 , wherein the light chain CDR1, CDR2, and CDR3 are according to SEQ ID NOs: 833, 834, and 779, respectively. 
     
     
         33 . The isolated antibody or antigen binding fragment of  claim 32 , wherein the antibody or antigen binding fragment thereof comprises a light chain, excluding the CDRs, at least 95% identical to SEQ ID NO: 832. 
     
     
         34 . The isolated antibody or antigen binding fragment of  claim 33 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain, excluding the CDRs, at least 95% identical to SEQ ID NO: 437. 
     
     
         35 . An isolated antibody or antigen binding fragment thereof that binds to cannabinoid receptor 1 (CB1), wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising:
 a heavy chain CDR1 comprising an amino acid sequence according to SEQ ID NO: 352;   a heavy chain CDR2 comprising an amino acid sequence according to SEQ ID NO: 353;   a heavy chain CDR3 comprising an amino acid sequence according to SEQ ID NO:354;   a light chain CDR1 comprising an amino acid sequence according to SEQ ID NOs: 355 or 833;   a light chain CDR2 comprising an amino acid sequence according to SEQ ID NOs: 356, 694, 834, or 835; and   a light chain CDR3 comprising an amino acid sequence according to SEQ ID NOs: 357, 779, or 836;   
       wherein the light chain CDR1, CDR2 and CDR3 are not simultaneously SEQ ID NO:355, 356 and 357 and wherein the antibody or antigen binding fragment thereof comprises at least one of the following:
 a light chain variable region comprising an amino acid sequence that is, excluding the CDRs, at least 95% identical to SEQ ID NO: 337, and 
 a heavy chain variable region comprising an amino acid sequence that is, excluding the CDRs, at least 95% identical to SEQ ID NO: 339, 340 or 341. 
 
     
     
         36 . A method reducing CB1 receptor signaling a subject in need thereof, wherein the subject has obesity, type 2 diabetes, fibrosis, and non-alcoholic steatohepatitis (NASH), the method comprising administering to the subject an antibody or antigen binding fragment of  claim 22 . 
     
     
         37 . The method of  claim 36 , wherein the subject has obesity. 
     
     
         38 . The method of  claim 36 , wherein subject has type 2 diabetes. 
     
     
         39 . The method of  claim 36 , wherein the subject has obesity liver fibrosis. 
     
     
         40 . The method of  claim 36 , wherein the subject has obesity NASH. 
     
     
         41 . The method of  claim 36 , wherein the subject has kidney fibrosis.