Compositions and methods relating to universal glycoforms for enhanced antibody efficacy

Abstract

The present disclosure relates to compositions and methods of use comprising antibodies or binding fragments thereof further comprising universal Fc glycoforms.

What is claimed is: 
     
         1 . An isolated monoclonal antibody or a binding fragment thereof that binds to Neu5Acα2→3Galβ1→3GalNAcβ1→3Galα1→4Galβ1→4Glcβ1 wherein the antibody or the fragment thereof comprises a Fc glycoform for enhancing binding/effector activity in monoclonal antibody, wherein said antibody comprising a glycoform having the formula: 
       
         
           
           
               
               
           
         
       
     
     
         2 . The isolated antibody of  claim 1 , wherein the antibody is an IgG1 and the binding to Neu5Acα2→3Galβ1→3GalNAcβ1→3Galα1→4Galβ1 is specific binding. 
     
     
         3 . The isolated antibody of  claim 2  wherein the antibody comprised V H  having SEQ ID NO: 147 or SEQ ID No:137 and V L  having SEQ ID No: 148 or SEQ ID No:138. 
     
     
         4 . The isolated antibody, or antigen-binding fragment thereof of  claim 3 , comprising H-CDR1, H-CDR2, and H-CDR3 selected from (i)-(iii):
 (i) H-CDR1 selected from SEQ ID NO:152 (GFSLTSYG);   (ii) H-CDR2 selected from SEQ ID NO: 153 (IWGEGST);   (iii) H-CDR3 selected from SEQ ID NO:154 (AMTGTAY), respectively;   and comprising L-CDR1, L-CDR2 and L-CDR3 selected from (iv)-(vi):   (iv) L-CDR1 selected from SEQ ID NO: 149 (SSVSY);   (v) L-CDR2 selected from SEQ ID NO:150 (DTS); and   (vi) L-CDR3 selected from SEQ ID NO: 151 (HQWSSSPHT), respectively.   
     
     
         5 . The isolated antibody or antigen-binding fragment of  claim 4  wherein the antibody or the antigen binding fragment further comprising H-FR1, H-FR2, H-FR3, and HFR4 selected from (i)-(iv):
 (i) H-FR1 selected from SEQ ID NO:159 (QVQLKESGPGLVAPSQSLSITCTVS); 
 (ii) H-FR2 selected from SEQ ID NO:160 (VSWIRQPPGKGLEWIGV); 
 (iii) H-FR3 selected from SEQ ID NO:161 (NYHSVLISRLTISKDNSKSQVFLKLNSLQTDDTATYYC); 
 (iv) H-FR4 selected from SEQ ID NO:162 (WGQGTLVTVSS); respectively; 
 and comprising L-FR1, L-FR2, L-FR3 and L-FR4 selected from (v)-(viii): 
 (v) L-FR1 selected from SEQ ID NO: 155 (QIVLTQSPAIMSASPGEKVTMTCSAS); 
 (vi) L-FR2 selected from SEQ ID NO:156 (MHWYQQKSGTSPKRWIY); 
 (vii) L-FR3 selected from SEQ ID NO: 157 (KLSSGVPGRFSGSGSGTSYSLTISRLEAEDAATYYC); 
 (viii) L-FR4 selected from SEQ ID NO: 158 (FGGGTKVEIKR); respectively. 
 
     
     
         6 . The antibody of  claim 5  wherein the antibody is a human antibody. 
     
     
         7 . The antibody of  claim 5  wherein the antibody is a humanized antibody. 
     
     
         8 . The isolated antibody of  claim 2  wherein the antibody comprised V H  having SEQ ID NO: 202, SEQ ID No. 212 or SEQ ID No: 222 and V L  having SEQ ID No: 203 SEQ ID No. 213 or SEQ ID No: 223. 
     
     
         9 . The isolated antibody, or antigen-binding fragment thereof of  claim 8 , comprising H-CDR1, H-CDR2, and H-CDR3 selected from (i)-(iii):
 (i) H-CDR1 selected from SEQ ID NO:207, SEQ ID NO: 217, SEQ ID NO: 227;   (ii) H-CDR2 selected from SEQ ID NO: 208; SEQ ID NO: 218, SEQ ID NO: 228;   (iii) H-CDR3 selected from SEQ ID NO: 209, SEQ ID NO: 219, SEQ ID NO: 229; respectively;   and comprising L-CDR1, L-CDR2 and L-CDR3 selected from (iv)-(vi):   (iv) L-CDR1 selected from SEQ ID NO: 204; SEQ ID NO: 214, and SEQ ID NO: 224;   (v) L-CDR2 selected from SEQ ID NO:205; SEQ ID NO: 215 and SEQ ID NO: 225;   (vi) L-CDR3 selected from SEQ ID NO: 206, SEQ ID NO: 216 and SEQ ID NO: 226; respectively.   
     
     
         10 . The antibody of  claim 9  wherein the antibody is a human antibody. 
     
     
         11 . The antibody of  claim 9  wherein the antibody is a humanized antibody. 
     
     
         12 . The isolated antibody of  claim 1 , wherein the antigen binding fragment is a Fab fragment, a F(ab′)2 fragment, or a single-chain Fv fragment. 
     
     
         13 . A pharmaceutical composition comprising the monoclonal antibody or binding fragment thereof of any one of  claim 6 ,  7 ,  10 , or  11  and a pharmaceutically acceptable carrier. 
     
     
         14 . The pharmaceutical composition of  claim 13  wherein the composition is useful in the treatment against a hyperproliferative disease. 
     
     
         15 . A method of treating cancer in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of the pharmaceutical composition of  claim 13  whereby the administered antibody enhances ADCC activity in said subject. 
     
     
         16 . The method of  claim 15 , wherein the cancer is selected from the group consisting of brain cancer, lung cancer, breast cancer, oral cancer, esophageal cancer, stomach cancer, liver cancer, bile duct cancer, pancreatic cancer, colon cancer, kidney cancer, bone cancer, skin cancer, cervical cancer, ovarian cancer, and prostate cancer. 
     
     
         17 . The composition of  claim 16  wherein the method comprising optionally administering a combined pharmaceutical formulation with at least one other chemotherapeutic agent. 
     
     
         18 . A method for making a population of homogeneous antibodies of  claim 13  comprising:
 (a) contacting a monoclonal antibody with an α-fucosidase and at least one endoglycosidase; 
 (b) generating a defucosylated antibody having a single N-acetylglucosamine (GlcNAc); and 
 (c) adding the universal glycan to GlcNAc of Fc region of antibody to form the homogeneous antibody with said glycoform. 
 
     
     
         19 . The antibody or binding fragment thereof of  claim 1 , wherein the antibodies includes antibodies or binding fragments thereof specifically bind to one or more of the antigens selected from the group consisting of Globo H, SSEA-3 and SSEA-4.