Cytostatin II

Abstract

The invention relates to cytostatin II growth modulatory polypeptides, polynucleotides encoding the polypeptides, methods for producing the polypeptides, in particular by expressing the polynucleotides, and agonists and antagonists of the polypeptides. The invention further relates to methods for utilizing such polynucleotides, polypeptides, agonists and antagonists for applications, which relate, in part, to research, diagnostic and clinical arts.

1 . An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of: 
 (a) a nucleotide sequence encoding the cytostatin II polypeptide consisting of amino acid residues 1 to 132 of SEQ ID NO:2;    (b) a nucleotide sequence encoding the cytostatin II polypeptide consisting of a fragment of SEQ ID NO:2, wherein said fragment comprises at least 30 contiguous amino acid residues of SEQ ID NO:2;    (c) a nucleotide sequence encoding the cytostatin II polypeptide consisting of a fragment of SEQ ID NO:2, wherein said fragment comprises at least 50 contiguous amino acid residues of SEQ ID NO:2;    (d) a nucleotide sequence encoding the cytostatin II polypeptide consisting of the full-length polypeptide encoded by the cDNA contained in ATCC™ Deposit Number 97287;    (e) a nucleotide sequence encoding the cytostatin II polypeptide consisting of the mature form of the polypeptide encoded by the cDNA contained in ATCC™ Deposit Number 97287;    (f) a nucleotide sequence encoding the cytostatin II polypeptide consisting of a fragment of the polypeptide encoded by the cDNA contained in ATCC™ Deposit Number 97287, wherein said fragment comprises at least 30 contiguous amino acid residues of the polypeptide encoded by the cDNA contained in ATCC™ Deposit Number 97287; and    (g) a nucleotide sequence encoding the cytostatin II polypeptide consisting of a fragment of the polypeptide encoded by the cDNA contained in ATCC™ Deposit Number 97287, wherein said fragment comprises at least 50 contiguous amino acid residues of the polypeptide encoded by the cDNA contained in ATCC™ Deposit Number 97287.    
     
     
         2 . A method for making a recombinant vector comprising inserting an isolated nucleic acid molecule of  claim 1  into a vector.  
     
     
         3 . A recombinant vector produced by the method of  claim 2 .  
     
     
         4 . A method of making a recombinant host cell comprising introducing the recombinant vector of  claim 3  into a host cell.  
     
     
         5 . A recombinant host cell produced by the method of  claim 4 .  
     
     
         6 . A recombinant method of producing a cytostatin II polypeptide, comprising culturing the recombinant host cell of  claim 5  under conditions such that said polypeptide is expressed and recovering said polypeptide.  
     
     
         7 . An isolated cytostatin II polypeptide comprising an amino acid sequence at least 95% identical to a sequence selected from the group consisting of: 
 (a) the amino acid sequence of the cytostatin II polypeptide consisting of amino acid residues 1 to 132 of SEQ ID NO:2;    (b) the amino acid sequence of the cytostatin II polypeptide consisting of a fragment of SEQ ID NO:2, wherein said fragment comprises at least 30 contiguous amino acid residues of SEQ ID NO:2;    (c) the amino acid sequence of the cytostatin II polypeptide consisting of a fragment of SEQ ID NO:2, wherein said fragment comprises at least 50 contiguous amino acid residues of SEQ ID NO:2;    (d) the amino acid sequence of the cytostatin II polypeptide consisting of the full-length polypeptide encoded by the cDNA contained in ATCC™ Deposit Number 97287;    (e) the amino acid sequence of the cytostatin II polypeptide consisting of the mature form of the polypeptide encoded by the cDNA contained in ATCC™ Deposit Number 97287;    (f) the amino acid sequence of the cytostatin II polypeptide consisting of a fragment of the polypeptide encoded by the cDNA contained in ATCC™ Deposit Number 97287, wherein said fragment comprises at least 30 contiguous amino acid residues of the polypeptide encoded by the cDNA contained in ATCC™ Deposit Number 97287; and    (g) the amino acid sequence of the cytostatin II polypeptide consisting of a fragment of the polypeptide encoded by the cDNA contained in ATCC™ Deposit Number 97287, wherein said fragment comprises at least 50 contiguous amino acid residues of the polypeptide encoded by the cDNA contained in ATCC™ Deposit Number 97287.    
     
     
         8 . The polypeptide of  claim 7 , wherein said polypeptide comprises a heterologous polypeptide.  
     
     
         9 . The polypeptide of  claim 7 , wherein said polypeptide is glycosylated.  
     
     
         10 . A composition comprising the polypeptide of  claim 7  and a pharmaceutically acceptable carrier.  
     
     
         11 . An isolated polypeptide produced by the method comprising: 
 (a) expressing the polypeptide of  claim 7  in a recombinant host cell comprising a nucleic acid molecule encoding said polypeptide; and    (b) recovering said polypeptide.    
     
     
         12 . An isolated antibody or fragment thereof that specifically binds to a cytostatin II polypeptide of  claim 7 .  
     
     
         13 . The antibody or fragment thereof of  claim 12  wherein said polypeptide bound by said antibody or fragment thereof is glycosylated.  
     
     
         14 . The antibody or fragment thereof of  claim 12  wherein said antibody or fragment thereof is human.  
     
     
         15 . The antibody or fragment thereof of  claim 12  wherein said antibody or fragment thereof is polyclonal.  
     
     
         16 . The antibody or fragment thereof of  claim 12  wherein said antibody or fragment thereof is monoclonal.  
     
     
         17 . The antibody or fragment thereof of  claim 12  which is selected from the group consisting of: 
 (a) a chimeric antibody or fragment thereof;    (b) a humanized antibody or fragment thereof;    (c) a single chain antibody; and    (d) a Fab fragment.    
     
     
         18 . The antibody or fragment thereof of  claim 12  wherein said antibody or fragment thereof binds to a cytostatin II polypeptide in a Western blot or an ELISA.  
     
     
         19 . A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject comprising: 
 (a) determining the presence or amount of expression of the cytostatin II polypeptide using the antibody or fragment thereof of  claim 12;  and    (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or amount of expression of the cytostatin II polypeptide.    
     
     
         20 . A method of inhibiting tumor growth in a subject having a tumor susceptible to growth inhibition by cytostatin II, said method comprising administering to said subject an amount of cytostatin II polypeptide of  claim 7  sufficient to inhibit growth of said tumor.