Methods and compositions for treating allergic diseases

Abstract

Disclosed in the present invention are antibodies that specifically recognize and antagonize human TSLP receptor, and methods of employing these antibodies to treat or ameliorate diseases or disorder mediated by TSLP signaling.

1 . An isolated polynucleotide encoding a polypeptide comprising the variable region of the heavy chain or the variable region of the light chain of an antibody or antigen binding portion thereof, wherein said antibody or antigen binding portion thereof comprises heavy chain CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9, respectively; and light chain CDR1, CDR2 and CDR3 sequences comprising the sequences of SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12, respectively; wherein the isolated antibody or antigen binding portion thereof binds specifically to human thymic stromal lymphopoietin receptor. 
     
     
         2 . The isolated polynucleotide of  claim 1 , wherein said polynucleotide encoding a polypeptide comprising a heavy chain variable region of an antibody comprising the sequence of amino acids 10 to 134 of SEQ ID NO: 5. 
     
     
         3 . The isolated polynucleotide of  claim 1 , wherein said polynucleotide encoding a polypeptide comprising a light chain variable region comprising the sequence of amino acids 21 to 128 of SEQ ID NO: 6. 
     
     
         4 . The isolated polynucleotide of  claim 1 , wherein said antibody is a mouse antibody. 
     
     
         5 . The isolated polynucleotide of  claim 1 , wherein said antibody is a chimeric antibody. 
     
     
         6 . The isolated polynucleotide of  claim 1 , wherein said antibody comprises a human heavy chain constant region and a human light chain constant region. 
     
     
         7 . The isolated polynucleotide of  claim 1 , wherein said antibody is a humanized antibody. 
     
     
         8 . The isolated polynucleotide of  claim 1 , wherein said antibody is a single chain antibody. 
     
     
         9 . The isolated polynucleotide of  claim 1 , wherein said antibody is a Fab fragment. 
     
     
         10 . The isolated polynucleotide of  claim 1 , wherein said antibody is of the IgG1 or IgG4 isotype. 
     
     
         11 . The isolated polynucleotide of  claim 1 , wherein said antibody is a monoclonal antibody. 
     
     
         12 . The isolated polynucleotide of  claim 1 , wherein said polynucleotide is a DNA. 
     
     
         13 . An isolated host cell comprising the polynucleotide of  claim 1 . 
     
     
         14 . An isolated host cell comprising (1) a recombinant DNA segment encoding a heavy chain of an antibody; and (2) a second recombinant DNA segment encoding a light chain of said antibody; wherein said DNA segments are respectively operably linked to a first and a second promoter, and are capable of being expressed in said host cell; and wherein said antibody comprises heavy chain CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising the sequences of SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12, respectively. 
     
     
         15 . The host cell of  claim 14 , wherein said antibody is a monoclonal humanized antibody. 
     
     
         16 . The host cell of  claim 14 , wherein said host cell is a non-human mammalian cell line. 
     
     
         17 . A method of treating an inflammatory disorder in a subject, the method comprises administering to the subject a pharmaceutical composition comprising an effective amount of an antibody or antigen binding portion thereof, wherein said antibody or antigen binding portion thereof comprises heavy chain CDR 1, CDR2 and CDR3 sequences of SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9, respectively, and light chain CDR1, CDR2 and CDR3 sequences comprising the sequences of SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12, respectively, wherein the isolated antibody or antigen binding portion thereof binds specifically to human thymic stromal lymphopoietin receptor. 
     
     
         18 . The method of  claim 17 , wherein said antibody is a humanized antibody. 
     
     
         19 . The method of  claim 17 , wherein said antibody comprising a heavy chain variable region of an antibody comprising the sequence of amino acids 10 to 134 of SEQ ID NO: 5, and a light chain variable region comprising the sequence of amino acids 10 to 128 of SEQ ID NO: 6. 
     
     
         20 . The method of  claim 17 , wherein the subject is human.