Novel proteins, gene encoding the same and method of utilization thereof

Abstract

The present invention provides, as a gene encoding an antigen recognized by G-CSF-inducing antibodies, a gene encoding: (a) a protein having the amino acid sequence listed as SEQ ID NO:2 of the Sequence Listing; (b) a protein having the amino acid sequence listed as SEQ ID NO:2 of the Sequence Listing with one or more amino acid deletions, substitutions, additions or insertions and also binding to an antibody or its fragment that is active to induce granulocyte colony-stimulating factor; or (c) a protein having at least 50% homology with the amino acid sequence listed as SEQ ID NO:2 and also binding to an antibody or its fragment that is active to induce granulocyte colony-stimulating factor.

1 . A gene encoding: 
 (a) a protein having the amino acid sequence listed as SEQ ID NO:4 of the Sequence Listing;    (b) a protein having the amino acid sequence listed as SEQ ID NO:4 of the Sequence Listing with one or more amino acid deletions, substitutions, additions or insertions and also binding to an antibody or its fragment that is active to induce granulocyte colony-stimulating factor; or    (c) a protein having at least 50% homology with the amino acid sequence listed as SEQ ID NO:4 and also binding to an antibody or its fragment that is active to induce granulocyte colony-stimulating factor.    
     
     
         2 . A gene having: 
 (a) the nucleotide sequence listed as SEQ ID NO:3 of the Sequence Listing;    (b) a nucleotide sequence which is the nucleotide sequence listed as SEQ ID NO:3 of the Sequence Listing with one or more nucleotide deletions, substitutions, additions or insertions and which encodes a protein that can bind to an antibody or its fragment that is active to induce granulocyte colony-stimulating factor; or    (c) a nucleotide sequence which hybridizes with DNA having the nucleotide sequence listed as SEQ ID NO:3 of the Sequence Listing under stringent conditions and encodes a protein that can bind to an antibody or its fragment that is active to induce granulocyte colony-stimulating factor.    
     
     
         3 . A DNA fragment containing: 
 (1) the nucleotide sequence from position 519 to position 736, the nucleotide sequence from position 666 to position 689, the nucleotide sequence from position 381 to position 403 or the nucleotide sequence from position 709 to position 727 of the nucleotide sequence listed as SEQ ID NO:1 of the Sequence Listing;    (2) a nucleotide sequence which is any of the nucleotide sequences of (1) with one or more nucleotide deletions, substitutions, additions or insertions; or    (3) a nucleotide sequence which has at least 80% homology with any of the nucleotide sequences of (1).    
     
     
         4 . A gene containing: 
 (1) the nucleotide sequence from position 519 to position 736, the nucleotide sequence from position 666 to position 689, the nucleotide sequence from position 381 to position 403 or the nucleotide sequence from position 709 to position 727 of the nucleotide sequence listed as SEQ ID NO:1 of the Sequence Listing;    (2) a nucleotide sequence which is any of the nucleotide sequences of (1) with one or more nucleotide deletions, substitutions, additions or insertions; or    (3) a nucleotide sequence which has at least 80% homology with any of the nucleotide sequences of (1),    and encoding a protein that can bind to an antibody or its fragment that is active to induce granulocyte colony-stimulating factor.    
     
     
         5 . Any of the following proteins: 
 (a) a protein having the amino acid sequence listed as SEQ ID NO:4 of the Sequence Listing;    (b) a protein having the amino acid sequence listed as SEQ ID NO:4 of the Sequence Listing with one or more amino acid deletions, substitutions, additions or insertions and also binding to an antibody or its fragment that is active to induce granulocyte colony-stimulating factor;    (c) a protein having at least 50% homology with the amino acid sequence listed as SEQ ID NO:4 and also binding to an antibody or its fragment that is active to induce granulocyte colony-stimulating factor; or    (d) a protein that is encoded by the DNA which hybridizes with DNA having the nucleotide sequence listed as SEQ ID NO:3 of the Sequence Listing under stringent conditions and that binds to an antibody or its fragment that is active to induce granulocyte colony-stimulating factor.    
     
     
         6 . A protein comprising any of the followings: 
 (1) the amino acid sequence from residues 1 to 91, the amino acid sequence from residues 50 to 146, the amino acid sequence from residues 1 to 78, the amino acid sequence from residues 200 to 241, the amino acid sequence from residues 172 to 241, the amino acid sequence from residues 103 to 150 or the amino acid sequence from residues 169 to 241 of the amino acid sequence listed as SEQ ID NO:2 of the Sequence Listing;    (2) an amino acid sequence which is any of the amino acid sequences of (1) with one or more amino acid deletions, substitutions, additions or insertions; or    (3) an amino acid sequence having at least 70% homology with any of the amino acid sequences of (1).    
     
     
         7 . A protein comprising any of the followings: 
 (1) the amino acid sequence from residues 1 to 91, the amino acid sequence from residues 50 to 146, the amino acid sequence from residues 1 to 78, the amino acid sequence from residues 200 to 241, the amino acid sequence from residues 172 to 241, the amino acid sequence from residues 103 to 150 or the amino acid sequence from residues 169 to 241 of the amino acid sequence listed as SEQ ID NO:2 of the Sequence Listing;    (2) an amino acid sequence which is any of the amino acid sequences of (1) with one or more amino acid deletions, substitutions, additions or insertions; or    (3) an amino acid sequence having at least 70% homology with any of the amino acid sequences of (1), and also binding to an antibody or its fragment that is active to induce granulocyte colony-stimulating factor.    
     
     
         8 . An antibody against a protein according to  claim 5 , or a fragment thereof.  
     
     
         9 . An antibody or fragment thereof according to  claim 8 , which is a monoclonal antibody.  
     
     
         10 . An antibody or fragment thereof according to  claim 9 , which is a human-type monoclonal antibody or human monoclonal antibody.  
     
     
         11 . Any of the following substances obtained by a screening method, which is characterized by measurement of binding between a substance and a protein according to  claim 5:   (a) a substance which can bind to a protein according to  claim 5 , and as a result of its binding to the protein, it can cause a change in the protein structure, transmit signals into the cell via the protein, and induce production of granulocyte colony-stimulating factor;    (b) a substance which can bind to a protein according to  claim 5 , and as a result of its binding to the protein, it can inhibit the binding of the protein to the substances that can induce production of granulocyte colony-stimulating factor, but it in itself does not induce production of granulocyte colony-stimulating factor; or    (c) a substance which can bind to a protein according to  claim 5 , and as a result of its binding to the protein, it can inhibit the binding of the protein to the substances that can induce production of granulocyte colony-stimulating factor, but it in itself blocks production of granulocyte colony-stimulating factor.    
     
     
         12 . Any of the following substances that can bind to a protein according to  claim 5:   (a) a substance which, as a result of its binding to the protein, it can cause a change in the protein structure, transmit signals into the cell via the protein, and induce production of granulocyte colony-stimulating factor;    (b) a substance which, as a result of its binding to the protein, it can inhibit the binding of the protein to the substances that can induce production of granulocyte colony-stimulating factor, but it in itself does not induce production of granulocyte colony-stimulating factor; or    (c) a substance which, as a result of its binding to the protein, it can inhibit the binding of the protein to the substances that can induce production of granulocyte colony-stimulating factor, but it in itself blocks production of granulocyte colony-stimulating factor.    
     
     
         13 . A pharmaceutical composition comprising a gene of  claim 1  or  2 , a DNA fragment of  claim 3 , or a protein of  claim 5 , which is used for diagnosis, prevention or treatment of a disease or condition related to G-CSF, such as infection or neutropenia.  
     
     
         14 . A method of diagnosis, prevention or treatment of a disease or a condition related to G-CSF, such as infection or neutropenia, which employs a gene or DNA fragment according to any one of  claims 1  to  4 , a protein according to any one of  claims 5  to  8 , or an antibody or its fragment according to any one of  claims 9  to  10 .