Antibodies That Inhibit TSLP Activity

Abstract

The invention is directed to purified and isolated novel TSLP polypeptides, the nucleic acids encoding such polypeptides, processes for production of recombinant forms of such polypeptides, antibodies generated against these polypeptides, fragmented peptides derived from these polypeptides, and the uses of the above.

What is claimed is: 
     
         1 . An isolated nucleic acid molecule selected from the group consisting of:
 (a) the DNA sequence of SEQ ID NO: 1;   (b) an isolated nucleic acid molecule encoding an amino acid sequence comprising the sequence of SEQ ID NO:2;   (c) an isolated nucleic acid molecule that hybridizes to either strand of a denatured, double-stranded DNA comprising the nucleic acid sequence of (a) or (b) under condition of moderate stringency in 50% formamide and 6×SSC, at 42° C. with washing conditions of 60° C., 0.5×SSC, 0.1% SDS;   (d) an isolated nucleic acid molecule derived by in vitro mutagenesis from SEQ ID NO:1;   (e) an isolated nucleic acid molecule degenerate from SEQ ID NO:1 as a result of the genetic code; and   (f) an isolated nucleic acid molecule selected from the group consisting of human TSLP DNA, an allelic variant of human TSLP DNA, and a species homolog of TSLP DNA.   
     
     
         2 . The nucleic acid molecule of  claim 1  comprising the DNA sequence of SEQ ID NO:1. 
     
     
         3 . A recombinant vector that directs the expression of the nucleic acid molecule of  claim 1 . 
     
     
         4 . An isolated polypeptide encoded by the nucleic acid molecule of  claim 1 . 
     
     
         5 . An isolated polypeptide according to  claim 4  having a molecular weight of approximately 21,000 Daltons as determined by SDS-PAGE. 
     
     
         6 . An isolated polypeptide according to  claim 4  in non-glycosylated form. 
     
     
         7 . An isolated antibody that binds to a polypeptide of  claim 4 . 
     
     
         8 . An antibody to  claim 7 , wherein the antibody is a monoclonal antibody. 
     
     
         9 . A purified TSLP polypeptide selected from the group consisting of:
 a) the TSLP polypeptide of SEQ ID NO:2; and   b) a fragment of the polypeptide of (a), wherein said fragment is capable of binding TSLP receptors.   
     
     
         10 . An isolated TSLP polypeptide comprising an amino acid sequence that is at least 80% identical to the amino acid sequence presented in SEQ ID NO:2. 
     
     
         11 . A TSLP polypeptide of  claim 9 , wherein said polypeptide comprises the amino acid sequence of SEQ ID NO:2. 
     
     
         12 . A composition comprising a polypeptide of  claim 4 , and a physiologically acceptable diluent, excipient, or carrier. 
     
     
         13 . A host cell transfected or transduced with the vector of  claim 3 . 
     
     
         14 . A method for the production of TSLP polypeptide comprising culturing the host cell of  claim 13  under conditions promoting expression, and recovering the polypeptide from the culture medium. 
     
     
         15 . The method of  claim 14 , wherein the host cell is selected from the group consisting of bacterial cells, yeast cells, plant cells, and animal cells. 
     
     
         16 . A method of stimulating lymphocyte proliferation, comprising incubating lymphocytes with the polypeptide according to  claim 4 . 
     
     
         17 . The method of  claim 16 , further comprising incubating the lymphocytes with IL-7. 
     
     
         18 . The method of  claim 16 , further comprising incubating the lymphocytes with a cytokine selected from the group consisting of Steel Factor, Stem Cell Factor, Mast Growth Factor or flt3-Ligand. 
     
     
         19 . A method of stimulating lymphocyte development or lymphopoiesis comprising incubating progenitor cells with the polypeptide according to  claim 4 . 
     
     
         20 . The method of  claim 19 , wherein the progenitor cells are bone marrow-derived mononuclear cells. 
     
     
         21 . The method of  claim 20 , further comprising incubating the bone marrow derived mononuclear cells with IL-7. 
     
     
         22 . A method of stimulating lymphocyte proliferation, comprising incubating lymphocytes with the polypeptide according to  claim 4  and  1 L-7. 
     
     
         23 . A method of stimulating lymphocyte development or lymphopoiesis comprising incubating progenitor cells with the polypeptide according to  claim 4  and IL-7.