Anti-il-22ra antibodies and binding partners and methods of using in inflammation

Abstract

The present invention relates to blocking, inhibiting, reducing, antagonizing or neutralizing the activity of IL-22, IL-20, or both IL-20 and IL-22 polypeptide molecules. IL-20 and IL-22 are cytokines that are involved in inflammatory processes and human disease. IL-22RA (zcytor11) is a common receptor for IL-20 and IL-22. The present invention includes anti-IL-22RA antibodies and binding partners, as well as methods for antagonizing IL-22 or both IL-20 and IL-22 using such antibodies and binding partners.

1 . A method of producing an antibody to a polypeptide comprising:
 inoculating an animal with a polypeptide selected from the group consisting of:   (a) a polypeptide consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 1 (Pro), to amino acid number 6 (Asp);   (b) a polypeptide consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 26 (Ser), to amino acid number 32 (Pro);   (c) a polypeptide consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 41 (Lys), to amino acid number 47 (Asp);   (d) a polypeptide consisting of the amino acid sequence of SEQ ID NO:2 from amino acid number 49 (Val), to amino acid number 62 (Cys);   (e) a polypeptide consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 41 (Lys) to amino acid number 62 (Cys);   (f) a polypeptide consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 84 (Ala) to amino acid number 97 (Ser);   (g) a polypeptide consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 103 (Thr) to amino acid number 108 (Asp);   (h) a polypeptide consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 130 (Arg) to amino acid number 135 (His);   (i) a polypeptide consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 164 (Gly) to amino acid number 166 (Lys);   (j) a polypeptide consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 175 (Tyr), to amino acid number 179 (Glu);   (k) a polypeptide consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 193 (Lys) to amino acid number 196 (Ala);   (l) a polypeptide consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 203 (Lys) to amino acid number 209 (Thr);   (m) a polypeptide consisting of the amino acid sequence of SEQ ID NO:3; and   (n) a polypeptide consisting of the amino acid sequence of SEQ ID NO:4; and   wherein the polypeptide elicits an immune response in the animal to produce the antibody; and   isolating the antibody from the animal; and   wherein the antibody specifically binds to an IL-22RA polypeptide (SEQ ID NO:2 or SEQ ID NO:3); and reduces the activity of either IL-20 (SEQ ID NO:8) or IL-22 (SEQ ID NO:6).   
     
     
         2 . The method according to  claim 1 , wherein the antibody produced by the method reduces the pro-inflammatory activity of either IL-20 (SEQ ID NO:8) or IL-22 (SEQ ID NO:6). 
     
     
         3 . The method of  claim 1 , wherein the antibody produced by the method neutralizes the interaction of either IL-20 (SEQ ID NO:8) or IL-22 (SEQ ID NO:6) with IL-22RA (SEQ ID NO:2). 
     
     
         4 . The method of  claim 3 , wherein the neutralization by the antibody is measured by showing neutralization of either IL-20 (SEQ ID NO:8) or IL-22 (SEQ ID NO:6) in an in vitro a cell-based neutralization assay. 
     
     
         5 . The method of  claim 1 , wherein the antibody produced by the method reduces the pro-inflammatory activity of both IL-20 (SEQ ID NO:8) and IL-22 (SEQ ID NO:6). 
     
     
         6 . The method of  claim 1 , wherein the antibody produced by the method neutralizes the interaction of both IL-20 (SEQ ID NO:8) and IL-22 (SEQ ID NO:6) with IL-22RA (SEQ ID NO:2). 
     
     
         7 . The method of  claim 3 , wherein the neutralization by the antibody is measured by showing neutralization of both IL-20 (SEQ ID NO:8) and IL-22 (SEQ ID NO:6) in an in vitro a cell-based neutralization assay. 
     
     
         8 . A method of suppressing an inflammatory response in a mammal with inflammation comprising:
 (1) determining a level of serum amyloid A protein;   (2) administering a composition comprising an antibody according to  claim 3  in an acceptable pharmaceutical vehicle;   (3) determining a post administration level of serum amyloid A protein;   (4) comparing the level of serum amyloid A protein in step (1) to the level of serum amyloid A protein in step (3),   wherein a lack of increase or a decrease in serum amyloid A protein level is indicative of suppressing an inflammatory response.   
     
     
         9 . A method of suppressing an inflammatory response in a mammal with inflammation comprising:
 (1) determining a level of serum amyloid A protein;   (2) administering a composition comprising an antibody according to  claim 5  in an acceptable pharmaceutical vehicle;   (3) determining a post administration level of serum amyloid A protein;   (4) comparing the level of serum amyloid A protein in step (1) to the level of serum amyloid A protein in step (3),   wherein a lack of increase or a decrease in serum amyloid A protein level is indicative of suppressing an inflammatory response.   
     
     
         10 . A method of suppressing an inflammatory response in a mammal with inflammation comprising:
 (1) determining a level of serum amyloid A protein;   (2) administering a composition comprising an antibody that binds to a polypeptide comprising a sequence of amino acid residues as shown in SEQ ID NO: 3 and reduces the pro-inflammatory activity of either IL-20 (SEQ ID NO: 8) or IL-22 (SEQ ID NO: 6) in an acceptable pharmaceutical vehicle;   (3) determining a post administration level of serum amyloid A protein;   (4) comparing the level of serum amyloid A protein in step (1) to the level of serum amyloid A protein in step (3),   wherein a lack of increase or a decrease in serum amyloid A protein level is indicative of suppressing an inflammatory response.   
     
     
         11 . A method of suppressing an inflammatory response in a mammal with inflammation comprising:
 (1) determining a level of serum amyloid A protein;   (2) administering a composition comprising an antibody that binds to a polypeptide comprising a sequence of amino acid residues as shown in SEQ ID NO: 3 and reduces the pro-inflammatory activity of both IL-20 (SEQ ID NO: 8) and IL-22 (SEQ ID NO: 6) in an acceptable pharmaceutical vehicle;   (3) determining a post administration level of serum amyloid A protein;   (4) comparing the level of serum amyloid A protein in step (1) to the level of serum amyloid A protein in step (3),   wherein a lack of increase or a decrease in serum amyloid A protein level is indicative of suppressing an inflammatory response.   
     
     
         12 . A method of treating a pathological condition in a subject associated with IL-22RA activity comprising administering an effective amount of a monoclonal antibody that specifically binds to an antigenic epitope of human IL-22RA (SEQ ID NO: 3) selected from the group consisting of:
 (a) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number I (Pro), to amino acid number 6 (Asp);   (b) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 26 (Ser), to amino acid number 32 (Pro);   (c) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 41 (Lys), to amino acid number 47 (Asp);   (d) an epitope consisting of the amino acid sequence of SEQ ID NO:2 from amino acid number 49 (Val), to amino acid number 62 (Cys);   (e) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 41 (Lys) to amino acid number 62 (Cys);   (f) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 84 (Ala) to amino acid number 97 (Ser);   (g) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 103 (Thr) to amino acid number 108 (Asp);   (h) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 130 (Arg) to amino acid number 135 (His);   (i) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 164 (Gly) to amino acid number 166 (Lys);   (j) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 175 (Tyr), to amino acid number 179 (Glu);   (k) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 193 (Lys) to amino acid number 196 (Ala);   (l) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 203 (Lys) to amino acid number 209 (Thr);   (m) an epitope consisting of the amino acid sequence of SEQ ID NO:3; and   (n) an epitope consisting of the amino acid sequence of SEQ ID NO:4; and   wherein the antibody reduces or neutralizes the activity of either human IL-22 (SEQ ID NO:6) or IL-20 (SEQ ID NO:8),   thereby treating said pathological condition.   
     
     
         13 . The method of  claim 12 , wherein said pathological condition is a chronic inflammatory condition. 
     
     
         14 . The method of  claim 13 , wherein said chronic inflammatory condition comprising inflammatory bowel disease, ulcerative colitis, Crohn's disease, arthritis, atopic dermatitis, or psoriasis. 
     
     
         15 . The method of  claim 12 , wherein said pathological condition is an acute inflammatory condition. 
     
     
         16 . The method of  claim 15 , wherein said acute inflammatory condition comprises endotoxemia, septicemia, toxic shock syndrome, or infectious disease. 
     
     
         17 . A method of reducing inflammation comprising administering to a mammal with inflammation an amount sufficient to reduce inflammation of a composition of a monoclonal antibody that specifically binds to an antigenic epitope of human IL-22RA (SEQ ID NO: 3) selected from the group consisting of:
 (a) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number I (Pro), to amino acid number 6 (Asp);   (b) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 26 (Ser), to amino acid number 32 (Pro);   (c) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 41 (Lys), to amino acid number 47 (Asp);   (d) an epitope consisting of the amino acid sequence of SEQ ID NO:2 from amino acid number 49 (Val), to amino acid number 62 (Cys);   (e) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 41 (Lys) to amino acid number 62 (Cys);   (f) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 84 (Ala) to amino acid number 97 (Ser);   (g) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 103 (Thr) to amino acid number 108 (Asp);   (h) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 130 (Arg) to amino acid number 135 (His);   (i) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 164 (Gly) to amino acid number 166 (Lys);   (j) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 175 (Tyr), to amino acid number 179 (Glu);   (k) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 193 (Lys) to amino acid number 196 (Ala);   (l) an epitope consisting of the amino acid sequence of SEQ ID NO:3 from amino acid number 203 (Lys) to amino acid number 209 (Thr);   (m) an epitope consisting of the amino acid sequence of SEQ ID NO:3; and   (n) an epitope consisting of the amino acid sequence of SEQ ID NO:4; and   wherein the antibody reduces or neutralizes the activity of either human IL-22 (SEQ ID NO:6) or IL-20 (SEQ ID NO:8).