Anti-ccl17 antibodies

Abstract

The present invention relates to antibodies specifically binding CCL17, polynucleotides encoding the antibodies or fragments, and methods of making and using the foregoing.

1 - 31 . (canceled) 
     
     
         32 . An isolated antibody or antigen-binding fragment thereof that specifically binds human CCL17, comprising a heavy chain variable region (VH) having an amino acid sequence that is at least 90% identical to SEQ ID NO: 46 and a light chain variable region (VL) having an amino acid sequence that is at least 90% identical to SEQ ID NO: 62, wherein the antibody or antigen binding portion thereof binds human CCL17 with an affinity constant (K D ) of about 1'10 −1  M or less, when the K D  is measured using solution equilibrium affinity in tris-based saline buffer containing 0.05% Tween-20 after co-incubation of the antibody and human CCL17 for 48 hours at 4° C., and wherein the isolated antibody blocks the interaction of CCL17 to CCR4 without blocking the interaction of CCL22 to CCR4. 
     
     
         33 . The antibody or antigen-binding fragment thereof of  claim 32 , wherein the antibody or antigen-binding fragment thereof binds human CCL17 with a K D  of about 5×10 −12  M or less. 
     
     
         34 . The antibody or antigen-binding fragment thereof of  claim 33 , wherein the antibody binds Macaca fascicularis (cyno) CCL17 with a K D  of about 1×10 −8  M or less, when the K D  is measured using solution equilibrium affinity in tris-based saline buffer containing 0.05% Tween-20 after co-incubation of the antibody and cyno CCL17 for 48 hours at 4° C. 
     
     
         35 . The antibody or antigen-binding fragment thereof of  claim 32 , wherein the amino acid sequence of the VH is at least 95% identical to SEQ ID NO: 46. 
     
     
         36 . The antibody or antigen-binding fragment thereof of  claim 32 , wherein the amino acid sequence of the VL is at least 95% identical to SEQ ID NO: 62. 
     
     
         37 . The antibody or antigen-binding fragment thereof of  claim 32 , wherein the amino acid sequence of the VH is at least 98% identical to SEQ ID NO: 46. 
     
     
         38 . The antibody or antigen-binding fragment thereof of  claim 32 , wherein the amino acid sequence of the VL is at least 98% identical to SEQ ID NO: 62. 
     
     
         39 . The antibody or antigen-binding fragment thereof of  claim 32 , wherein the antibody or antigen-binding fragment thereof is of an IgG1, IgG2, IgG3, or IgG4 isotype. 
     
     
         40 . The antibody or antigen-binding fragment thereof of  claim 32 , wherein the antibody comprises a substitution in an Fc region. 
     
     
         41 . The antibody or antigen-binding fragment thereof of  claim 32 , wherein the substitution comprises a V234A, G237A, P238S, H268A, V309L, A330S, or P331S substitution on IgG2, or a S228P, L234A, or L235A substitution on IgG4, wherein residue numbering is according to the EU Index. 
     
     
         42 . The antibody or antigen-binding fragment thereof of  claim 32 , wherein the substitution comprises a V234A/G237A/P238S/H268A/V309L/A330S/P331S substitution on IgG2 or a S228P/L234A/L235A substitution on IgG4, wherein residue numbering is according to the EU Index. 
     
     
         43 . A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of  claim 32  and a pharmaceutically accepted carrier. 
     
     
         44 . One or more isolated polynucleotide(s) encoding the VH and the VL of the antibody or antigen-binding fragment thereof of  claim 32 . 
     
     
         45 . A vector comprising the polynucleotide of  claim 44 . 
     
     
         46 . A host cell for producing an isolated antibody or antigen-binding fragment thereof comprising the vector of  claim 45 . 
     
     
         47 . A method of producing an antibody or antigen-binding fragment thereof, comprising culturing the host cell of  claim 46  under conditions such that the antibody or antigen-binding fragment thereof is produced.