Anti-il-22r antibodies

Abstract

The present invention relates to antibodies and antigen binding fragments thereof which bind to the cytokine receptor IL-22R, particularly human IL-22R. The invention also relates to pharmaceutical compositions comprising said antibodies or antigen binding fragments thereof, and methods of treating psoriasis, psoriatic arthritis or atopic dermatitis.

1 . An antibody, or an antigen binding fragment thereof, which binds to human IL-22R protein, wherein the antibody or antigen binding fragment thereof binds to an epitope within the IL-22R protein that does not include Tyr60. 
     
     
         2 . The antibody or antigen binding fragment of  claim 1 , which binds to an epitope within the IL-22R protein comprising amino acids from the D2 domain of the protein, wherein the D2 domain is from amino acid 125 to amino acid 228 of SEQ ID NO:71. 
     
     
         3 . The antibody or antigen binding fragment of  claim 1 , which binds to human IL-22R with high affinity. 
     
     
         4 . The antibody or antigen binding fragment of  claim 3 , which comprises at least one heavy chain variable domain (VH) and at least one light chain variable domain (VL), wherein said VH domain and VL domain when tested as a mAb exhibit an off-rate (k off ) for human IL-22R of less than 2×10 −3  s −1 . 
     
     
         5 . The antibody or antigen binding fragment of  claim 3 , which comprises at least one heavy chain variable domain (VH) and at least one light chain variable domain (VL), wherein said VH domain and VL domain when tested as a mAb exhibit an off-rate (k off ) for human IL-22R in the range 1×10 −6  s −1  to 2×10 −3  s −1 . 
     
     
         6 . The antibody or antigen binding fragment of  claim 1 , which blocks binding of IL-22 to human IL-22R. 
     
     
         7 . The antibody or antigen binding fragment of  claim 1 , which inhibits IL-22-dependent activation of IL-22R or IL-20-dependent activation of IL-22R. 
     
     
         8 . The antibody or antigen binding fragment of  claim 1 , which inhibits IL-22-dependent activation of IL-22R and IL-20-dependent activation of IL-22R. 
     
     
         9 . The antibody or antigen binding fragment of  claim 7 , which comprises at least one heavy chain variable domain (VH) and at least one light chain variable domain (VL), wherein said VH domain and VL domain when tested as a mAb exhibit an IC 50  for IL-22-dependent activation of less than 500 pM and/or an IC 50  for IL-20-dependent activation of less than 500 pM. 
     
     
         10 . The antibody or antigen binding fragment of  claim 1 , which does not cross-react with murine IL-22R. 
     
     
         11 - 13 . (canceled) 
     
     
         14 . The antibody or antigen-binding fragment of  claim 1  comprising a combination of variable heavy chain CDR sequences: HCDR3 comprising SEQ ID NO: 6; HCDR2 comprising SEQ ID NO: 36; and HCDR1 comprising SEQ ID NO: 34, and a combination of variable light chain CDR sequences: LCDR3 comprising SEQ ID NO: 54; LCDR2 comprising SEQ ID NO: 47; and LCDR1 comprising SEQ ID NO: 16. 
     
     
         15 - 20 . (canceled) 
     
     
         21 . The antibody or antigen binding fragment of  claim 1  wherein the antibody or antigen binding fragment thereof comprises a combination of a heavy chain variable domain (VH) and a light chain variable domain (VL) selected from the following:
 (i) a VH comprising the amino acid sequence of SEQ ID NO: 63 or an amino acid sequence at least 90%, 95%, 97%, 98% or 99% identical thereto and a VL comprising the amino acid sequence of SEQ ID NO: 64 or an amino acid sequence at least 90%, 95%, 97%, 98% or 99% identical thereto; 
 (ii) a VH comprising the amino acid sequence of SEQ ID NO: 65 or an amino acid sequence at least 90%, 95%, 97%, 98% or 99% identical thereto and a VL comprising the amino acid sequence of SEQ ID NO: 66 or an amino acid sequence at least 90%, 95%, 97%, 98% or 99% identical thereto. 
 
     
     
         22 . An antibody according to  claim 1  comprising
 at least one heavy chain and at least one light chain selected from the following: 
 (i) a heavy chain comprising the amino acid sequence of SEQ ID NO: 67 or an amino acid sequence at least 90%, 95%, 97%, 98% or 99% identical thereto and a light chain comprising the amino acid sequence of SEQ ID NO: 68 or an amino acid sequence at least 90%, 95%, 97%, 98% or 99% identical thereto; 
 (ii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 69 or an amino acid sequence at least 90%, 95%, 97%, 98% or 99% identical thereto and a light chain comprising the amino acid sequence of SEQ ID NO: 70 or an amino acid sequence at least 90%, 95%, 97%, 98% or 99% identical thereto. 
 
     
     
         23 . An antibody or an antigen binding fragment thereof, which binds to IL-22R, wherein the antibody or antigen binding fragment comprises a heavy chain variable domain comprising at least one complementarity determining region (CDR) selected from SEQ ID NOs: 2, 4, 6, 9, 11, 13, 34, 36, 41, 43 or sequence variants thereof, wherein the sequence variant comprises one, two or three amino acid substitutions in the recited sequence. 
     
     
         24 - 26 . (canceled) 
     
     
         27 . The antibody or antigen binding fragment of  claim 23  which comprises a light chain variable domain comprising at least one complementarity determining region (CDR) selected from SEQ ID NOs: 16, 18, 20, 23, 25, 27, 47, 54, 57, 59 or sequence variants thereof, wherein the sequence variant comprises one, two or three amino acid substitutions in the recited sequence. 
     
     
         28 - 30 . (canceled) 
     
     
         31 . The antibody or antigen binding fragment of  claim 23 , comprising a combination of variable heavy chain CDR3 (HCDR3), variable heavy chain CDR2 (HCDR2) and variable heavy chain CDR1 (HCDR1) wherein the combination is selected from the group consisting of:
 (i) HCDR3 comprising SEQ ID NO: 6; HCDR2 comprising SEQ ID NO: 36; HCDR1 comprising SEQ ID NO: 34;   (ii) HCDR3 comprising SEQ ID NO: 43; HCDR2 comprising SEQ ID NO: 41; HCDR1 comprising SEQ ID NO: 9;   (iii) HCDR3 comprising SEQ ID NO: 6; HCDR2 comprising SEQ ID NO: 4; HCDR1 comprising SEQ ID NO: 2; and   (iv) HCDR3 comprising SEQ ID NO: 13; HCDR2 comprising SEQ ID NO: 11; HCDR1 comprising SEQ ID NO: 9.   
     
     
         32 . The antibody or antigen-binding fragment of  claim 31 , comprising a light chain variable domain comprising a combination of variable light chain CDR3 (LCDR3), variable light chain CDR2 (LCDR2) and variable light chain CDR1 (LCDR1) selected from the group consisting of:
 (i) LCDR3 comprising SEQ ID NO: 54; LCDR2 comprising SEQ ID NO: 47; LCDR1 comprising SEQ ID NO: 16;   (ii) LCDR3 comprising SEQ ID NO: 27; LCDR2 comprising SEQ ID NO: 59; LCDR1 comprising SEQ ID NO: 57;   (iii) LCDR3 comprising SEQ ID NO: 20; LCDR2 comprising SEQ ID NO: 47; LCDR1 comprising SEQ ID NO: 16;   (iv) LCDR3 comprising SEQ ID NO: 20; LCDR2 comprising SEQ ID NO: 18; LCDR1 comprising SEQ ID NO: 16; and   (v) LCDR3 comprising SEQ ID NO: 27; LCDR2 comprising SEQ ID NO: 25; LCDR1 comprising SEQ ID NO: 23.   
     
     
         33 - 39 . (canceled) 
     
     
         40 . The antibody or antigen binding fragment of  claim 23  wherein the antibody or antigen binding fragment thereof comprises a combination of a heavy chain variable domain (VH) and a light chain variable domain (VL) selected from the following: a VH comprising the amino acid sequence of SEQ ID NO: 63 or an amino acid sequence at least 90%, 95%, 97%, 98% or 99% identical thereto and a VL comprising the amino acid sequence of SEQ ID NO: 64 or an amino acid sequence at least 90%, 95%, 97%, 98% or 99% identical thereto. 
     
     
         41 . (canceled) 
     
     
         42 . An antibody according to  claim 23  comprising at least one heavy chain and at least one light chain selected from the following: a heavy chain comprising the amino acid sequence of SEQ ID NO: 67 or an amino acid sequence at least 90%, 95%, 97%, 98% or 99% identical thereto and a light chain comprising the amino acid sequence of SEQ ID NO: 68 or an amino acid sequence at least 90%, 95%, 97%, 98% or 99% identical thereto. 
     
     
         43 . (canceled) 
     
     
         44 . An antibody or antigen-binding fragment thereof, which binds to the same epitope as the antibody of  claim 23 . 
     
     
         45 . The antibody or antigen-binding fragment of  claim 23  wherein the antibody or antigen binding fragment thereof exhibits at least one or more of the following properties:
 (i) binds to an epitope within the IL-22R protein that does not include Tyr60; 
 (ii) binds to human IL-22R with high affinity; 
 (iii) blocks binding of IL-22 to IL-22R; 
 (iv) inhibits IL-22-dependent activation of IL-22R and/or IL-20-dependent activation of IL-22R; 
 (v) does not cross-react with murine IL-22R. 
 
     
     
         46 . The antibody or antigen binding fragment of  claim 23  which contains the hinge region, CH2 domain and/or CH3 domain of a human IgG. 
     
     
         47 - 59 . (canceled) 
     
     
         60 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising Ala209. 
     
     
         61 . The antibody or antigen-binding fragment thereof of  claim 1 , wherein the antibody or antigen-binding fragment thereof binds to an epitope comprising Arg112.