Antibodies to mica and micb proteins

Abstract

This present disclosure relates to binding agents, particularly antibodies, which bind to MICA and/or MICB; compositions comprising the binding agents; and use of the binding agents for diagnostics and in treatments of diseases characterized by elevated MICA and/MICB proteins.

1 .- 38 . (canceled) 
     
     
         39 . A method of preparing an antibody that binds specifically to soluble MICA (sMICA) and/or soluble MICB (sMICB) protein, the method comprising:
 determining binding of an antibody to sMICA and/or sMICB;   determining binding of the antibody to membrane-bound MICA and/or membrane-bound MICB; and   isolating the antibody that binds specifically to sMICA and/or sMICB but does not bind or binds nonspecifically to membrane-bound MICA and/or membrane-bound MICB.   
     
     
         40 . The method of  claim 39 , wherein the antibody binds to the alpha-3 domain of sMICA. 
     
     
         41 . The method of  claim 40 , wherein the antibody binds specifically to an epitope within amino acid residues 190 to 256 of the alpha-3 domain of MICA, wherein the amino acid position is based on unprocessed MICA*001 allele. 
     
     
         42 . The method of  claim 41 , wherein the antibody binds specifically to an epitope within amino acid residues 217 to 238 of MICA, wherein the amino acid positions are with respect to mature, processed MICA protein of the MICA*001 allele. 
     
     
         43 . The method of  claim 39 , wherein the antibody binds to the alpha-3 domain of sMICB. 
     
     
         44 . The method of  claim 43 , wherein the antibody binds specifically to an epitope within amino acid residues 190 to 256 of the alpha-3 domain of MICB, wherein the amino acid position is based on unprocessed MICB*001 allele. 
     
     
         45 . The method of  claim 44 , wherein the antibody binds specifically to an epitope within amino acid residues 217 to 238 of MICB, wherein the amino acid positions are with respect to mature, processed MICB protein of the MICB*001 allele. 
     
     
         46 . The method of  claim 39 , wherein the membrane bound MICA and/or membrane bound MICB protein is cell membrane bound MICA and cell membrane bound MICB, respectively. 
     
     
         47 . A method of screening an antibody that binds specifically to soluble MICA (sMICA) or soluble MICB (sMICB), comprising:
 (a) obtaining at least one antibody that bind to sMICA and/or sMICB;   (b) determining whether the one or more antibodies of (a) has the properties of
 (i) nonspecific or absence of binding to membrane-bound MICA and/or membrane-bound MICB protein; and 
 (ii) binding to alpha-3 domain of sMICA and/or sMICB; 
   (c) selecting the antibody that has properties of (i) and (ii); and   (d) isolating the antibody that binds specifically to sMICA and/or sMICB.   
     
     
         48 . The method of  claim 47 , wherein the antibody binds specifically to the alpha-3 domain of sMICA. 
     
     
         49 . The method of  claim 40 , wherein the antibody binds specifically to an epitope within amino acid residues 190 to 256 of the alpha-3 domain of MICA, wherein the amino acid positions are based on unprocessed MICA*001 allele. 
     
     
         50 . The method of  claim 49 , wherein the antibody binds specifically to an epitope within amino acid residues 217 to 238 of MICA, wherein the amino acid position are based on mature, processed MICA protein of the MICA* 001 allele. 
     
     
         51 . The method of  claim 47 , wherein the antibody binds specifically to the alpha-3 domain of sMICB. 
     
     
         52 . The method of  claim 51 , wherein the antibody binds specifically to an epitope within amino acid residues 190 to 256 of the alpha-3 domain of MICB, wherein the amino acid positions are based on unprocessed MICB*001 allele. 
     
     
         53 . The method of  claim 52 , wherein the antibody binds specifically to an epitope within amino acid residues 217 to 238 of MICB, wherein the amino acid positions are based on mature, processed MICB protein of the MICB*001 allele. 
     
     
         54 . The method of  claim 47 , wherein the membrane bound MICA and/or membrane bound MICB protein is cell membrane-bound MICA and cell membrane-bound MICB, respectively.