Cytostatin I

Abstract

A human cytostatin I polypeptide and DNA encoding such polypeptide and a procedure for producing such polypeptide by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptide for the treatment of cancers, particularly breast cancer, leukemias, and other matastases.

What is claimed is:  
     
         1 . An isolated antibody or portion thereof that specifically binds to a protein whose sequence consists of amino acid residues +1 to +107 of SEQ ID NO:2.  
     
     
         2 . The antibody or portion thereof of  claim 1  wherein said protein specifically bound by said antibody or portion thereof is glycosylated.  
     
     
         3 . The antibody or portion thereof of  claim 1  which is a monoclonal antibody.  
     
     
         4 . The antibody or portion thereof of  claim 1  which is a polyclonal antibody.  
     
     
         5 . The antibody or portion thereof of  claim 1  which is a chimeric antibody.  
     
     
         6 . The antibody or portion thereof of  claim 1  which is a single chain antibody.  
     
     
         7 . The antibody or portion thereof of  claim 1  which is a Fab fragment.  
     
     
         8 . The antibody or portion thereof of  claim 1  which is labeled.  
     
     
         9 . The antibody of  claim 8  wherein the label is selected from the group consisting of: 
 (a) an enzyme label;  
 (b) a radioisotope; and  
 (c) a fluorescent label.  
 
     
     
         10 . A composition comprising the antibody or portion thereof of  claim 1  and a carrier.  
     
     
         11 . The composition of  claim 10 , wherein the antibody or portion thereof is a monoclonal antibody.  
     
     
         12 . The composition of  claim 10 , wherein the antibody or portion thereof is a polyclonal antibody.  
     
     
         13 . The composition of  claim 10 , wherein the antibody or portion thereof is a chimeric antibody.  
     
     
         14 . The composition of  claim 10 , wherein the antibody or portion thereof is a single chain antibody.  
     
     
         15 . The composition of  claim 10 , wherein the antibody or portion thereof is a Fab fragment.  
     
     
         16 . The composition of  claim 10 , wherein the antibody or portion thereof is labeled.  
     
     
         17 . The composition of  claim 16  wherein the label is selected from the group consisting of: 
 (a) an enzyme label;  
 (b) a radioisotope; and  
 (c) a fluorescent label.  
 
     
     
         18 . An isolated cell that produces the antibody of  claim 1 .  
     
     
         19 . A hybridoma that produces the antibody of  claim 1 .  
     
     
         20 . A hybridoma that produces the antibody of  claim 3 .  
     
     
         21 . A method of detecting Cytostatin I protein in a biological sample comprising: 
 (a) contacting the biological sample with the antibody or portion thereof of  claim 1;  and    (b) detecting the Cytostatin I protein in the biological sample.    
     
     
         22 . The method of  claim 21  wherein the antibody is a monoclonal antibody.  
     
     
         23 . The method of  claim 21  wherein the antibody is a polyclonal antibody.  
     
     
         24 . The method of  claim 21  wherein the antibody is a chimeric antibody.  
     
     
         25 . The method of  claim 21  wherein the antibody is a single chain antibody.  
     
     
         26 . The method of  claim 21  wherein the antibody is a Fab fragment.  
     
     
         27 . The method of  claim 21  wherein the antibody is a labeled antibody.  
     
     
         28 . The method of  claim 27  wherein the label is selected from the group consisting of: 
 (a) an enzyme label;  
 (b) a radioisotope; and  
 (c) a fluorescent label.  
 
     
     
         29 . An isolated antibody or portion thereof produced by immunizing an animal with a protein whose sequence comprises amino acid residues +1 to +107 of SEQ ID NO:2; wherein said antibody or portion thereof specifically binds to the amino acid sequence of SEQ ID NO:2.  
     
     
         30 . An isolated antibody or portion thereof that specifically binds to a protein selected from the group consisting of: 
 (a) a protein whose sequence consists of amino acid residues +39 to +107 of SEQ ID NO:2;    (b) a protein whose sequence consists of amino acid residues +22 to +107 of SEQ ID NO:2;    (c) a protein whose sequence consists of 30 contiguous amino acid residues of SEQ ID NO:2; and    (d) a protein whose sequence consists of 50 contiguous amino acid residues of SEQ ID NO:2.    
     
     
         31 . The isolated antibody or portion thereof of  claim 30 , that specifically binds protein (a).  
     
     
         32 . The isolated antibody or portion thereof of  claim 30 , that specifically binds protein (b).  
     
     
         33 . The isolated antibody or portion thereof of  claim 30 , that specifically binds protein (c).  
     
     
         34 . The isolated antibody or portion thereof of  claim 30 , that specifically binds protein (d).  
     
     
         35 . The isolated antibody or portion thereof of  claim 30 , wherein said protein specifically bound by said isolated antibody or portion thereof is glycosylated.  
     
     
         36 . The isolated antibody or portion thereof of  claim 30  which is a monoclonal antibody.  
     
     
         37 . The isolated antibody or portion thereof of  claim 30  which is a polyclonal antibody.  
     
     
         38 . The isolated antibody or portion thereof of  claim 30 , which is a chimeric antibody.  
     
     
         39 . The isolated antibody or portion thereof of  claim 30  which is a single chain antibody.  
     
     
         40 . The isolated antibody or portion thereof of  claim 30  which is a Fab fragment.  
     
     
         41 . The antibody or portion thereof of  claim 30  which is labeled.  
     
     
         42 . The antibody of  claim 41  wherein the label is selected from the group consisting of: 
 (a) an enzyme label;  
 (b) a radioisotope; and  
 (c) a fluorescent label.  
 
     
     
         43 . A composition comprising the isolated antibody or portion thereof of  claim 30  and a carrier.  
     
     
         44 . The composition of  claim 43 , wherein the isolated antibody or portion thereof is a monoclonal antibody.  
     
     
         45 . The composition of  claim 43 , wherein the isolated antibody or portion thereof is a polyclonal antibody.  
     
     
         46 . The composition of  claim 43 , wherein the isolated antibody or portion thereof is a chimeric antibody.  
     
     
         47 . The composition of  claim 43 , wherein the isolated antibody or portion thereof is a single chain antibody.  
     
     
         48 . The composition of  claim 43 , wherein the isolated antibody or portion thereof is a Fab fragment.  
     
     
         49 . The composition of  claim 43 , wherein the antibody or portion thereof is labeled.  
     
     
         50 . The composition of  claim 49  wherein the label is selected from the group consisting of: 
 (a) an enzyme label;  
 (b) a radioisotope; and  
 (c) a fluorescent label.  
 
     
     
         51 . An isolated cell that produces the antibody or portion thereof of  claim 30 .  
     
     
         52 . A hybridoma that produces the monoclonal antibody of  claim 30 .  
     
     
         53 . A hybridoma that produces the monoclonal antibody of  claim 36 .  
     
     
         54 . A method of assaying Cytostatin I protein in a biological sample comprising: 
 (a) contacting the biological sample with the isolated antibody or portion thereof of claim  30 ; and    (b) detecting Cytostatin I protein in the biological sample.    
     
     
         55 . The method of  claim 54  wherein the isolated antibody or portion thereof is a monoclonal antibody.  
     
     
         56 . The method of  claim 54  wherein the isolated antibody or portion thereof is a polyclonal antibody.  
     
     
         57 . The method of  claim 54  wherein the isolated antibody or portion thereof is a chimeric antibody.  
     
     
         58 . The method of  claim 54  wherein the isolated antibody or portion thereof is a single chain antibody.  
     
     
         59 . The method of  claim 54  wherein the isolated antibody or portion thereof is a Fab fragment.  
     
     
         60 . The method of  claim 54  wherein the isolated antibody or portion thereof is a labeled antibody.  
     
     
         61 . The method of  claim 60  wherein the label is selected from the group consisting of: 
 (a) an enzyme label;  
 (b) a radioisotope; and  
 (c) a fluorescent label.  
 
     
     
         62 . An antibody or portion thereof produced by immunizing an animal with a protein selected from the group consisting of: 
 (a) a protein whose sequence comprises amino acid residues +39 to +107 of SEQ ID NO:2;    (b) a protein whose sequence comprises amino acid residues +22 to +107 of SEQ ID NO:2;    (c) a protein whose sequence comprises 30 contiguous amino acid residues of SEQ ID NO:2; and    (d) a protein whose sequence comprises 50 contiguous amino acid residues of SEQ ID NO:2; 
 wherein said antibody or portion thereof specifically binds to the amino acid sequence of SEQ ID NO:2.  
   
     
     
         63 . The antibody or portion thereof of  claim 62  produced by immunizing an animal with protein (a).  
     
     
         64 . The antibody or portion thereof of  claim 62  produced by immunizing an animal with protein (b).  
     
     
         65 . The antibody or portion thereof of  claim 62  produced by immunizing an animal with protein (c).  
     
     
         66 . The antibody or portion thereof of  claim 62  produced by immunizing an animal with protein (d).  
     
     
         67 . An isolated antibody or portion thereof that specifically binds to a protein whose sequence consists of the amino acid sequence of the polypeptide encoded by the cDNA contained in ATCC®) Deposit No. 97103.  
     
     
         68 . The antibody or portion thereof of  claim 67  wherein said protein specifically bound by said antibody or portion thereof is glycosylated.  
     
     
         69 . The antibody or portion thereof of  claim 67  which is a monoclonal antibody.  
     
     
         70 . The antibody or portion thereof of  claim 67  which is a polyclonal antibody.  
     
     
         71 . The antibody or portion thereof of  claim 67  which is a chimeric antibody.  
     
     
         72 . The antibody or portion thereof of  claim 67  which is a single chain antibody.  
     
     
         73 . The antibody or portion thereof of  claim 67  which is a Fab fragment.  
     
     
         74 . The antibody or portion thereof of  claim 67  which is labeled.  
     
     
         75 . The antibody of  claim 74  wherein t he label is selected from the group consisting of: 
 (a) an enzyme label;  
 (b) a radioisotope; and  
 (c) a fluorescent label.  
 
     
     
         76 . A composition comprising the antibody or portion thereof of  claim 67  and a carrier.  
     
     
         77 . The composition of  claim 76 , wherein the antibody or portion thereof is a monoclonal antibody.  
     
     
         78 . The composition of  claim 76 , wherein the antibody or portion thereof is a polyclonal antibody.  
     
     
         79 . The composition of  claim 76 , wherein the antibody or portion thereof is a chimeric antibody.  
     
     
         80 . The composition of  claim 76 , wherein the antibody or portion thereof is a single chain antibody.  
     
     
         81 . The composition of  claim 76 , wherein the antibody or portion thereof is a Fab fragment.  
     
     
         82 . The composition of  claim 76 , wherein the antibody or portion thereof is labeled.  
     
     
         83 . The composition of  claim 82  wherein the label is selected from the group consisting of: 
 (a) an enzyme label;  
 (b) a radioisotope; and  
 (c) a fluorescent label.  
 
     
     
         84 . An isolated cell that produces the antibody of  claim 67 .  
     
     
         85 . A hybridoma that produces the antibody of  claim 67 .  
     
     
         86 . A hybridoma that produces the antibody of  claim 69 .  
     
     
         87 . A method of detecting Cytostatin I protein in a biological sample comprising: 
 (a) contacting the biological sample with the antibody or portion thereof of claim  67 ; and    (b) detecting the Cytostatin I protein in the biological sample.    
     
     
         88 . The method of  claim 87  wherein the antibody is a monoclonal antibody.  
     
     
         89 . The method of  claim 87  wherein the antibody is a polyclonal antibody.  
     
     
         90 . The method of  claim 87  wherein the antibody is a chimeric antibody.  
     
     
         91 . The method of  claim 87  wherein the antibody is a single chain antibody.  
     
     
         92 . The method of  claim 87  wherein the antibody is a Fab fragment.  
     
     
         93 . The method of  claim 87  wherein the antibody is a labeled antibody.  
     
     
         94 . The method of  claim 93  wherein the label is selected from the group consisting of: 
 (a) an enzyme label;  
 (b) a radioisotope; and  
 (c) a fluorescent label.  
 
     
     
         95 . An antibody or portion thereof produced by immunizing an animal with a protein whose sequence comprises the amino acid sequence of the polypeptide encoded by the cDNA contained in ATCC® Deposit No. 97103; wherein said antibody or portion thereof specifically binds to the amino acid sequence of the polypeptide encoded by the cDNA contained in ATCC® Deposit No. 97103.  
     
     
         96 . An isolated antibody or portion thereof that specifically binds to a protein selected from the group consisting of: 
 (a) a protein whose sequence consists of the amino acid sequence of the mature form of the polypeptide encoded by the cDNA contained in ATCC® Deposit No. 97103;    (b) a protein whose sequence consists of at least 30 contiguous amino acid residues of a polypeptide encoded by the cDNA contained in ATCC®) Deposit No. 97103; and    (c) a protein whose sequence consists of at least 50 contiguous amino acid residues of a polypeptide encoded by the cDNA contained in ATCC® Deposit No. 97103.    
     
     
         97 . The isolated antibody or portion thereof of  claim 96  that specifically binds protein (a).  
     
     
         98 . The isolated antibody or portion thereof of  claim 96  that specifically binds protein (b).  
     
     
         99 . The isolated antibody or portion thereof of  claim 96  that specifically binds protein (c).  
     
     
         100 . The isolated antibody or portion thereof of  claim 96 , wherein said protein specifically bound by said antibody or portion thereof is glycosylated.  
     
     
         101 . The isolated antibody or portion thereof of  claim 96 , which is a monoclonal antibody.  
     
     
         102 . The isolated antibody or portion thereof of  claim 96 , which is a polyclonal antibody.  
     
     
         103 . The isolated antibody or portion thereof of  claim 96 , which is a chimeric antibody.  
     
     
         104 . The isolated antibody or portion thereof of  claim 96  which is a single chain antibody.  
     
     
         105 . The isolated antibody or portion thereof of  claim 96  which is a Fab fragment.  
     
     
         106 . The isolated antibody or portion thereof of  claim 96  which is labeled.  
     
     
         107 . The isolated antibody or portion thereof of  claim 106  wherein the label is selected from the group consisting of: 
 (a) an enzyme label;  
 (b) a radioisotope; and  
 (c) a fluorescent label.  
 
     
     
         108 . A composition comprising the isolated antibody or portion thereof of  claim 96  and a carrier.  
     
     
         109 . The composition of  claim 108 , wherein the antibody or portion thereof is a monoclonal antibody.  
     
     
         110 . The composition of  claim 108 , wherein the antibody or portion thereof is a polyclonal antibody.  
     
     
         111 . The composition of  claim 108 , wherein the antibody or portion thereof is a chimeric antibody.  
     
     
         112 . The composition of  claim 108 , wherein the antibody or portion thereof is a single chain antibody.  
     
     
         113 . The composition of  claim 108 , wherein the antibody or portion thereof is a Fab fragment.  
     
     
         114 . An isolated cell that produces the antibody or portion thereof of  claim 96 .  
     
     
         115 . A hybridoma that produces the monoclonal antibody of  claim 96 .  
     
     
         116 . A hybridoma that produces the monoclonal antibody of  claim 101 .  
     
     
         117 . A method of assaying Cytostatin I protein in a biological sample comprising: 
 (a) contacting the biological sample from a test subject with the isolated antibody or portion thereof of claim  96 ; and    (b) detecting Cytostatin I protein in the biological sample.    
     
     
         118 . The method of  claim 117 , wherein the antibody or portion thereof is a monoclonal antibody.  
     
     
         119 . The method of  claim 117 , wherein the antibody or portion thereof is a polyclonal antibody.  
     
     
         120 . The method of  claim 117 , wherein the antibody or portion thereof is a chimeric antibody.  
     
     
         121 . The method of  claim 117 , wherein the antibody or portion thereof is a single chain antibody.  
     
     
         122 . The method of  claim 117 , wherein the antibody or portion thereof is a Fab fragment.  
     
     
         123 . An antibody or portion thereof produced by immunizing an animal with a protein selected from the group consisting of: 
 (a) a protein whose sequence comprises the amino acid sequence of the mature form of the polypeptide encoded by the cDNA contained in ATCC® Deposit Number 97103;    (b) a protein whose sequence comprises at least 30 contiguous amino acid residues of a polypeptide encoded by the cDNA contained in ATCC® Deposit No. 97103; and    (c) a protein whose sequence comprises at least 50 contiguous amino acid residues of a polypeptide encoded by the cDNA contained in ATCC® Deposit No. 97103; 
 wherein said antibody or portion thereof specifically binds to the polypeptide encoded by the cDNA contained in ATCC® Deposit No. 97103.  
   
     
     
         124 . (New) The antibody or portion thereof of  claim 123  produced by immunizing an animal with protein (a).  
     
     
         125 . (New) The antibody or portion thereof of  claim 123  produced by immunizing an animal with protein (b).  
     
     
         126 . (New) The antibody or portion thereof of  claim 123  produced by immunizing an animal with protein (c).  
     
     
         127 . A method of treating a patient having need of Cytostatin I protein.  
     
     
         128 . A method of treating a patient having need of a reduced level of Cytostatin I protein, comprising administering to said patient the antibody or portion thereof of  claim 1 .  
     
     
         129 . A method of treating a patient having need of a reduced level of Cytostatin I protein, comprising administering to said patient the antibody or portion thereof of  claim 30 .  
     
     
         130 . A method of treating a patient having need of a reduced level of Cytostatin I protein, comprising administering to said patient the antibody or portion thereof of  claim 67 .  
     
     
         131 . A method of treating a patient having need of a reduced level of Cytostatin I protein, comprising administering to said patient the antibody or portion thereof of claim  96 .