Kim-1 antibodies for treatment of th2-mediated conditions

Abstract

Compositions and methods for treating Th2- and Th1-mediated disease are provided.

1 . A method of treating a Th2-mediated disorder in a mammal, the method comprising administering to the mammal an antibody, or antigen-binding fragment thereof, that binds the stalk region of KIM-1. 
     
     
         2 . The method of  claim 1 , wherein the mammal is a human. 
     
     
         3 . The method of  claim 1 , wherein the disorder is atopy. 
     
     
         4 . The method of  claim 1 , wherein the disorder is asthma. 
     
     
         5 . The method of  claim 1 , wherein the antibody binds an epitope at least partially contained in the peptide DGNDTVTESSDGLWNNNQTQLFLEHSLLTANTTK (amino acids 236-269 of SEQ ID NO:1). 
     
     
         6 . The method of  claim 1 , wherein the antibody is a humanized or fully human monospecific antibody. 
     
     
         7 . The method of  claim 1 , wherein the antibody is a humanized or fully human monospecific antibody and wherein the antibody binds an epitope at least partially contained in the peptide DGNDTVTESSDGLWNNNQTQLFLEHSLLTANTTK (amino acids 236-269 of SEQ ID NO:1) 
     
     
         8 . The method of  claim 1 , wherein a full-length antibody is administered. 
     
     
         9 . The method of  claim 1 , wherein a full length antibody is administered and wherein the antibody binds an epitope at least partially contained in the peptide DGNDTVTESSDGLWNNNQTQLFLEHSLLTANTTK (amino acids 236-269 of SEQ ID NO:1) 
     
     
         10 . The method of  claim 1 , wherein an antigen-binding fragment of an antibody is administered. 
     
     
         11 . The method of  claim 1 , wherein an antigen-binding fragment of an antibody is administered and wherein the antibody binds an epitope at least partially contained in the peptide DGNDTVTESSDGLWNNNQTQLFLEHSLLTANTTK (amino acids 236-269 of SEQ ID NO:1). 
     
     
         12 - 13 . (canceled) 
     
     
         14 . The method of  claim 1 , wherein the antibody or antigen-binding fragment thereof is administered in combination with a second therapeutic agent for the disorder. 
     
     
         15 - 17 . (canceled) 
     
     
         18 . An isolated antibody, or antigen binding fragment thereof, that specifically binds the stalk region of KIM-1, wherein the antibody does not inhibit shedding of KIM-1 from E293 cells in culture. 
     
     
         19 . The method of  claim 1 , wherein the antibody binds to a peptide having a sequence selected from the group consisting of:
 (a) amino acids 262-270 of SEQ ID NO:1,   (b) amino acids 260-269 of SEQ ID NO:1,   (c) amino acids 257-270 of SEQ ID NO:1,   (d) amino acids 252-270 of SEQ ID NO:1,   (e) amino acids 236-250 of SEQ ID NO:1, and   (f) amino acids 236-258 of SEQ ID NO:1.   
     
     
         20 - 24 . (canceled) 
     
     
         25 . A method of treating a Th1-mediated disorder or reducing a pathogenic Th1 response in a mammal, the method comprising administering to the mammal an antibody, or antigen-binding fragment thereof, that binds the sequence VATSPSSPQPAETHPTTLQGAIRREPTSSPLYSYTT of human KIM-1 (amino acids 200-235 of SEQ ID NO:1) or an epitope overlapping said sequence. 
     
     
         26 - 31 . (canceled) 
     
     
         32 . A method of treating a Th2-mediated disorder in a mammal, the method comprising administering to the mammal an antibody, or antigen-binding fragment thereof, that binds the sialic acid binding motif of KIM-1. 
     
     
         33 . The method of  claim 32 , wherein the antibody binds at least partly to an epitope contained within or overlapping a peptide having the sequence GVYCCRVEHRGWFNDMKITVSLEIVPP (amino acids 81-107 of SEQ ID NO:1) or RGSCSLFTCQNGIV (amino acids 29-42 of SEQ ID NO:1). 
     
     
         34 . The method of  claim 32 , wherein the antibody binds a linear epitope of contiguous amino acid residues of GVYCCRVEHRGWFNDMKITVSLEIVPP (amino acids 81-107 of SEQ ID NO:1) or RGSCSLFTCQNGIV (amino acids 29-42 of SEQ ID NO:1). 
     
     
         35 . The method of  claim 32 , wherein the antibody binds a structural epitope to which one or both of the sequences GVYCCRVEHRGWFNDMKITVSLEIVPP (amino acids 81-107 of SEQ ID NO:1) and RGSCSLFTCQNGIV (amino acids 29-42 of SEQ ID NO:1) contribute. 
     
     
         36 . The method of  claim 32 , wherein the antibody protects amino acids 81-107 of SEQ ID NO:1. 
     
     
         37 - 46 . (canceled)