Engineered anti-il-23p19 antibodies

Abstract

Engineered antibodies to human IL-23p19 are provided, as well as uses thereof, e.g. in treatment of inflammatory, autoimmune, and proliferative disorders.

1 - 3 . (canceled) 
   
   
       4 . A binding compound that binds to human IL-23, comprising:
 a) an antibody light chain variable region, or antigen binding fragment thereof, comprising:   a CDRL1 selected from the group consisting of SEQ ID NOs: 80-82;   a CDRL2 selected from the group consisting of SEQ ID NOs: 83-85; and   a CDRL3 selected from the group consisting of SEQ ID NOs: 86-88; and   b) an antibody heavy chain variable region, or antigen binding fragment thereof, comprising:   CDRH1 of SEQ ID NO: 77;   CDRH2 of SEQ ID NO: 78; and   CDRH3 of SEQ ID NO: 79.   
   
   
       5 - 14 . (canceled) 
   
   
       15 . An antibody, or antigen binding fragment thereof, that is able to block binding of a binding compound to human IL-23 in a cross-blocking assay, wherein the binding compound comprises:
 a CDRL1 selected from the group consisting of SEQ ID NOs: 80-82;   a CDRL2 selected from the group consisting of SEQ ID NOs: 83-85;   a CDRL3 selected from the o consisting of SE ID NOs: 86-88;   CDRH1 of SEQ ID NO: 77;   CDRH2 of SEQ ID NO: 78; and   CDRH3 of SEQ ID NO: 79.   
   
   
       16 . The binding compound of  claim 4  wherein the binding compound blocks IL-23 mediated activity. 
   
   
       17 . An isolated nucleic acid encoding at least one of the light chain variable region or heavy chain variable region of the binding compound of  claim 4 . 
   
   
       18 - 19 . (canceled) 
   
   
       20 . A method of producing a polypeptide comprising:
 culturing a host cell comprising an expression vector comprising the nucleic acid of  claim 17  in culture medium under conditions wherein the nucleic acid sequence is expressed, thereby producing polypeptides comprising the light and heavy chain variable regions; and   recovering the polypeptides from the host cell or culture medium.   
   
   
       21 - 23 . (canceled) 
   
   
       24 . A method of suppressing an immune response in a human subject comprising administering to a subject in need thereof an antibody specific for IL-23, or a antigen binding fragment thereof, in an amount effective to block the biological activity of IL-23, wherein the antibody is the antibody of  claim 4 . 
   
   
       25 - 32 . (canceled) 
   
   
       33 . A binding compound that binds to human IL-23, comprising:
 a) an antibody light chain variable region, or antigen binding fragment thereof, comprising:   CDRL1 comprising residues 24-34 of SEQ ID NO: 112, or a variant thereof;   CDRL2 comprising residues 50-56 of SEQ ID NO: 112, or a variant thereof;   CDRL3 comprising residues 89-97 of SEQ ID NO: 112, or a variant thereof; and   b) an antibody heavy chain variable region, or antigen binding fragment thereof, comprising:   CDRH1 comprising residues 26-35 of SEQ ID NO: 99, or a variant thereof;   CDRH2 comprising residues 50-66 of a sequence selected from the group consisting of SEQ ID NOs: 99, 129 and 130, or a variant thereof; and   CDRH3 comprising residues 99-104 of SEQ ID NO: 99, or a variant thereof;   wherein each variant comprises up to five conservatively modified amino acid substitutions.   
   
   
       34 . The binding compound of  claim 33  wherein the binding compound comprises:
 a) an antibody light chain variable region, or antigen binding fragment thereof, comprising:   CDRL1 comprising residues 24-34 of SEQ ID NO: 112;   CDRL2 comprising residues 50-56 of SEQ ID NO: 112; and   CDRL3 comprising residues 89-97 of SEQ ID NO: 112; and   b) an antibody heavy chain variable region, or antigen binding fragment thereof, comprising:   CDRH1 comprising residues 26-35 of SEQ ID NO: 99;   CDRH2 comprising residues 50-66 of a sequence selected from the group consisting of SEQ ID NOs: 99, 129 and 130; and   CDRH3 comprising residues 99-104 of SEQ ID NO: 99.   
   
   
       35 . A binding compound that binds to human IL-23, comprising:
 a) an antibody light chain variable region, or antigen binding fragment thereof, comprising the sequence of SEQ ID NO: 131, or a variant thereof; and   b) an antibody heavy chain variable region, or antigen binding fragment thereof, comprising the sequence of SEQ ID NO: 129, 130, 132 or 133, or a variant thereof;   wherein each variant comprises up to 20 conservatively modified amino acid substitutions.   
   
   
       36 . The binding compound of  claim 35 , wherein the binding compound is an antibody or antigen binding fragment thereof comprising:
 a) a light chain variable region comprising the sequence of SEQ ID NO: 131; and   b) a heavy chain variable region comprising the sequence of SEQ ID NO: 129, 130, 132 or 133.   
   
   
       37 . The binding compound of  claim 35 , comprising:
 a) a light chain variable region consisting essentially of the sequence of SEQ ID NO: 131; and   b) a heavy chain variable region consisting essentially of the sequence of SEQ ID NO: 129, 130, 132 or 133.   
   
   
       38 - 39 . (canceled) 
   
   
       40 . An antibody, or antigen binding fragment thereof, that is able to block binding of a binding compound to human IL-23 in a cross-blocking assay, wherein the binding compound comprises:
 a) a light chain variable region comprising the sequence of SEQ ID NO: 131; and   b) a heavy chain variable region comprising the sequence of SEQ ID NO: 129, 130, 132 or 133.   
   
   
       41 . The binding compound of  claim 33  wherein the binding compound blocks IL-23 mediated activity. 
   
   
       42 . An isolated nucleic acid encoding at least one of the light chain variable region or heavy chain variable region of the binding compound of  claim 33 . 
   
   
       43 - 44 . (canceled) 
   
   
       45 . A method of producing a polypeptide comprising:
 culturing a host cell comprising an expression vector comprising the nucleic acid of  claim 42  in culture medium under conditions wherein the nucleic acid sequence is expressed, thereby producing polypeptides comprising the light and heavy chain variable regions; and   recovering the polypeptides from the host cell or culture medium.   
   
   
       46 - 47 . (canceled) 
   
   
       48 . The binding compound of  claim 33 , wherein the binding compound is an antibody fragment selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, scFv, F(ab′) 2 , and a diabody. 
   
   
       49 . A method of suppressing an immune response in a human subject comprising administering to a subject in need thereof an antibody specific. for IL-23, or a antigen binding fragment thereof, in an amount effective to block the biological activity of IL-23, wherein the antibody is the antibody of  claim 33 . 
   
   
       50 . The method of  claim 49 , wherein the immune response is an inflammatory response. 
   
   
       51 . The method of  claim 50 , wherein the subject has a disorder selected from the group consisting of arthritis, psoriasis and inflammatory bowel disease. 
   
   
       52 . The method of  claim 49 , wherein the immune response is an autoimmune response. 
   
   
       53 . The method of  claim 52 , wherein the subject has a disorder selected from the group consisting of multiple sclerosis, systemic lupus erythematosus and diabetes. 
   
   
       54 . The method of  claim 49 , wherein the subject has cancer and the immune response is a Th17 response. 
   
   
       55 - 57 . (canceled)