DcR3 polypeptide, a TNFR homolog

Abstract

A TNFR homolog, identified as DcR3, is provided. Nucleic acid molecules encoding DcR3, chimeric molecules and antibodies to DcR3 are also provided.

What is claimed is:  
     
         1 . An isolated DcR3 polypeptide having at least about 80% amino acid sequence identity with native sequence DcR3 polypeptide comprising amino acid residues 1 to 300 of FIG. 1 (SEQ ID NO:1).  
     
     
         2 . The DcR3 polypeptide of  claim 1  wherein said DcR3 polypeptide has at least about 90% amino acid sequence identity.  
     
     
         3 . The DcR3 polypeptide of  claim 2  wherein said DcR3 polypeptide has at least about 95% amino acid sequence identity.  
     
     
         4 . The DcR3 polypeptide of  claim 1  wherein said DcR3 polypeptide binds to Fas ligand.  
     
     
         5 . An isolated native sequence DcR3 polypeptide comprising amino acid residues 1 to 300 of FIG. 1 (SEQ ID NO:1).  
     
     
         6 . An isolated DcR3 polypeptide comprising amino acid residues 1 to 215 of FIG. 1 (SEQ ID NO:1).  
     
     
         7 . An isolated DcR3 polypeptide comprising amino acid residues 1 to X, wherein X is any one of amino acid residues 215 to 300 of FIG. 1 (SEQ ID NO:1).  
     
     
         8 . An isolated TNFR homolog comprising a polypeptide which includes one or more cysteine rich domains, wherein said one or more cysteine rich domains comprises the amino acid sequence of CRD1, CRD2, CDR3 or CRD4 shown in FIG. 6.  
     
     
         9 . A chimeric molecule comprising the DcR3 polypeptide of  claim 1  or the sequence of  claim 7  fused to a heterologous amino acid sequence.  
     
     
         10 . The chimeric molecule of  claim 9  wherein said heterologous amino acid sequence is an epitope tag sequence.  
     
     
         11 . The chimeric molecule of  claim 9  wherein said heterologous amino acid sequence is an immunoglobulin sequence.  
     
     
         12 . The chimeric molecule of  claim 11  wherein said immunoglobulin sequence is an IgG Fc domain.  
     
     
         13 . The chimeric molecule of  claim 11  wherein said sequence comprises amino acid residues 1 to 215 of FIG. 1 (SEQ ID NO:1).  
     
     
         14 . An antibody which binds to the DcR3 polypeptide of  claim 1  or the sequence of  claim 7 .  
     
     
         15 . The antibody of  claim 14  wherein said antibody is a monoclonal antibody.  
     
     
         16 . The antibody of  claim 14  which comprises a blocking antibody.  
     
     
         17 . The antibody of  claim 14  which comprises a chimeric antibody.  
     
     
         18 . The antibody of  claim 14  which comprises a human antibody.  
     
     
         19 . The antibody of  claim 15  having the biological characteristics of the 4C4.1.4 monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number ______.  
     
     
         20 . The antibody of  claim 15  having the biological characteristics of the 5C4.14.7 monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number ______.  
     
     
         21 . The antibody of  claim 15  having the biological characteristics of the 11C5.2.8 monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number ______.  
     
     
         22 . The antibody of  claim 15  having the biological characteristics of the 8D3.1.5 monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number ______.  
     
     
         23 . The antibody of  claim 15  having the biological characteristics of the 4B7.1.1 monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number ______.  
     
     
         24 . The antibody of  claim 15  wherein the antibody binds to the same epitope as the epitope to which the 4C4.1.4 monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number ______ binds.  
     
     
         25 . The antibody of  claim 15  wherein the antibody binds to the same epitope as the epitope to which the 5C4.14.7 monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number ______ binds.  
     
     
         26 . The antibody of  claim 15  wherein the antibody binds to the same epitope as the epitope to which the 11C5.2.8 monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number ______ binds.  
     
     
         27 . The antibody of claim is wherein the antibody binds to the same epitope as the epitope to which the 8D3.1.5 monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number ______ binds.  
     
     
         28 . The antibody of  claim 15  wherein the antibody binds to the same epitope as the epitope to which the 4B7.1.1 monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number ______ binds.  
     
     
         29 . A hybridoma cell line which produces the antibody of  claim 15 .  
     
     
         30 . The hybridoma cell line 4C4.1.4 deposited as ATCC accession number ______.  
     
     
         31 . The hybridoma cell line 5C4.14.7 deposited as ATCC accession number ______.  
     
     
         32 . The hybridoma cell line 11C5.2.8 deposited as ATCC accession number ______.  
     
     
         33 . The hybridoma cell line 8D3.1.5 deposited as ATCC accession number ______.  
     
     
         34 . The hybridoma cell line 4B7.1.1 deposited as ATCC accession number ______.  
     
     
         35 . The 4C4.1.4 monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number ______.  
     
     
         36 . The 5C4.14.7 monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number ______.  
     
     
         37 . The 11C5.2.8 monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number ______.  
     
     
         38 . The 8D3.1.5 monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number ______.  
     
     
         39 . The 4B7.1.1 monoclonal antibody produced by the hybridoma cell line deposited as ATCC accession number ______.  
     
     
         40 . Isolated nucleic acid comprising a nucleotide sequence encoding the DcR3 polypeptide of  claim 1  or the sequence of  claim 7 .  
     
     
         41 . The nucleic acid of  claim 40  wherein said nucleotide sequence encodes native sequence DcR3 polypeptide comprising amino acid residues 1 to 300 of FIG. 1 (SEQ ID NO:1).  
     
     
         42 . A vector comprising the nucleic acid of  claim 40 .  
     
     
         43 . The vector of  claim 42  operably linked to control sequences recognized by a host cell transformed with the vector.  
     
     
         44 . A host cell comprising the vector of  claim 42 .  
     
     
         45 . The host cell of  claim 44  which comprises a CHO cell.  
     
     
         46 . The host cell of  claim 44  which comprises a yeast cell.  
     
     
         47 . The host cell of  claim 44  which comprises an  E. coli.    
     
     
         48 . A process of using a nucleic acid molecule encoding DcR3 polypeptide to effect production of DcR3 polypeptide comprising culturing the host cell of  claim 44 .  
     
     
         49 . A non-human, transgenic animal which contains cells that express nucleic acid encoding DcR3 polypeptide.  
     
     
         50 . The animal of  claim 49  which is a mouse or rat.  
     
     
         51 . A non-human, knockout animal which contains cells having an altered gene encoding DcR3 polypeptide.  
     
     
         52 . The animal of  claim 51  which is a mouse or rat.  
     
     
         53 . A composition comprising the DcR3 of  claim 1  or  claim 7  and a carrier.  
     
     
         54 . A composition comprising the DcR3 antibody of  claim 14  and a carrier.  
     
     
         55 . An article of manufacture, comprising a container and a composition contained within said container, wherein the composition includes DcR3 polypeptide or DcR3 antibodies.  
     
     
         56 . The article of manufacture of  claim 55  further comprising instructions for using the DcR3 polypeptide or DcR3 antibodies in vivo or ex vivo.  
     
     
         57 . A method of modulating apoptosis in mammalian cells comprising exposing said cells to DcR3 polypeptide or a chimeric molecule comprising DcR3 polypeptide.  
     
     
         58 . A method of inhibiting Fas ligand induced apoptosis in mammalian cells comprising exposing said cells to DcR3 polypeptide or a chimeric molecule comprising DcR3 polypeptide.  
     
     
         59 . A method of inhibiting Fas ligand induced activity in mammalian cells comprising exposing said cells to DcR3 polypeptide or a chimeric molecule comprising DcR3 polypeptide.  
     
     
         60 . A method of treating mammalian cancer comprising exposing mammalian cancer cells to DcR3 antibodies.  
     
     
         61 . The method of  claim 60  wherein a DcR3 gene is amplified in said cancer cells.  
     
     
         62 . The method of  claim 60  wherein said mammalian cancer cells are lung cancer cells or colon cancer cells.  
     
     
         63 . The method of  claim 61  wherein said mammalian cancer cells are also exposed to chemotherapy or radiation therapy.  
     
     
         64 . A method of detecting or diagnosing cancer in a mammal comprising analyzing mammalian cells for amplification of a DcR3 gene.  
     
     
         65 . A method of inhibiting a T-cell mediated immune response in a mammal, comprising exposing mammalian cells to DcR3 polypeptide or a chimeric molecule comprising DcR3 polypeptide.  
     
     
         66 . An isolated nucleic acid comprising the nucleotide sequence of SEQ ID NO:3 or its complement.