Human FGF-21 gene and gene expression products

Abstract

This invention relates to human fibroblast growth factor (hFGF-21), and to variants thereof and to polynucleotides encoding FGF-2 1. The invention also relates to diagnostic and therapeutic agents related to the polynucleotides and proteins, including probes and antibodies, and to methods of treating liver disease such as cirrhosis and cancer, methods of treating conditions related to thymic function, and methods of treating conditions of the testis. The invention also relates to mouse fibroblast growth factor (mFGF-21), and to variants thereof and polynucleotides encoding mFGF-21.

1 - 11 . (canceled)  
     
     
         12 . An isolated polypeptide comprising amino acids at least 95% identical to amino acids selected from the group consisting of: 
 (a) amino acids from about 1 to about 209 of SEQ ID NO:4;    (b) amino acids from about 2 to about 209 of SEQ ID NO:4;    (c) amino acids from about 1 to about 177 of SEQ ID NO:4;    (d) amino acids from about 40 to about 209 of SEQ ID NO:4; and    (e) amino acids from about 40 to about 177 of SEQ ID NO:4.    
     
     
         13 . The isolated polypeptide of  claim 12  wherein, except for at least one conservative amino acid substitution, said polypeptide has an amino acid sequence selected from the group consisting of: 
 (a) amino acids from about 1 to about 209 of SEQ ID NO:4;    (b) amino acids from about 2 to about 209 of SEQ ID NO:4;    (c) amino acids from about 1 to about 177 of SEQ ID NO:4;    (d) amino acids from about 40 to about 209 of SEQ ID NO:4; and    (e) amino acids from about 40 to about 177 of SEQ ID NO:4.    
     
     
         14 . The isolated polypeptide of  claim 12  comprising amino acids selected from the group consisting of: 
 (a) amino acids from about 1 to about 209 of SEQ ID NO:4;    (b) amino acids from about 2 to about 209 of SEQ ID NO:4;    (c) amino acids from about 1 to about 177 of SEQ ID NO:4;    (d) amino acids from about 40 to about 209 of SEQ ID NO:4; and    (e) amino acids from about 40 to about 177 of SEQ ID NO:4.    
     
     
         15 - 18 . (canceled)  
     
     
         19 . An isolated antibody that binds specifically to the polypeptide of  claim 12 .  
     
     
         20 . An isolated antibody that binds specifically to the polypeptide of  claim 13 .  
     
     
         21 . An isolated antibody that binds specifically to the plypeptide of  claim 14 .  
     
     
         22 . A pharmaceutical composition comprising the polypeptide of  claim 12 , in combination with a pharmaceutically acceptable carrier.  
     
     
         23 . A method for providing trophic support for cells in a patient in need thereof, the method comprising administering to the patient a composition comprising a polynucleotide encoding the polypeptide of  claim 12 .  
     
     
         24 . The method of  claim 23  wherein said polynucleotide is administered by implanting cells which express said polynucleotide into the patient, wherein said cells express FGF-21 polypeptide in the patient.  
     
     
         25 - 31 . (canceled)  
     
     
         32 . A method for providing trophic support for cells in a patient in need thereof, the method comprising administering to the patient a composition comprising a polypeptide of  claim 12 .  
     
     
         33 - 34 . (canceled)  
     
     
         35 . A method of alleviating a disease condition in the liver of a human patient wherein said disease condition is alleviated by at least one method selected from the group consisting of slowing degeneration of, restoring function of, and increasing the number of, functional hepatic cells in said human patient, said method comprising administering to said patient a pharmaceutically effective composition comprising a polypeptide having the amino acid sequence of  claim 12 .  
     
     
         36 . A method of alleviating a disease condition in the thymus of a human patient wherein said disease condition is alleviated by at least one method selected from the group consisting of preventing degeneration of, slowing degeneration of, increasing the number of, functional thymic cells in said human patient, said method comprising administering to said patient a pharmaceutically effective composition a polypeptide having the amino acid sequence of  claim 12 .  
     
     
         37 . A method of alleviating a disease condition in the testis of a human patient wherein said disease condition is alleviated by at least one method selected from the group consisting of preventing degeneration of, slowing degeneration of, and increasing the number of, functional testicular cells in said human patient, said method comprising administering to said patient a pharmaceutically effective composition comprising a polypeptide having the amino acid sequence of  claim 12 .  
     
     
         38 - 39 . (canceled)  
     
     
         40 . A kit for detecting the presence of FGF-21 polypeptide in a sample from a patient, said kit comprising an antibody according to  claim 19 , packaged in a container.  
     
     
         41 - 51 . (canceled)  
     
     
         52 . An isolated polypeptide comprising amino acids at least 95% identical to amino acids selected from the group consisting of: 
 (a) amino acids from about 1 to about 210 of SEQ ID NO:2;    (b) amino acids from about 2 to about 210 of SEQ ID NO:2;    (c) amino acids from about 1 to about 177 of SEQ ID NO:2;    (d) amino acids from about 40 to about 210 of SEQ ID NO:2; and    (e) amino acids from about 40 to about 177 of SEQ ID NO:2.    
     
     
         53 . The isolated polypeptide of  claim 52  wherein, except for at least one conservative amino acid substitution, said polypeptide has an amino acid sequence selected from the group consisting of: 
 (a) amino acids from about 1 to about 210 of SEQ ID NO:2;    (b) amino acids from about 2 to about 210 of SEQ ID NO:2;    (c) amino acids from about 1 to about 177 of SEQ ID NO:2;    (d) amino acids from about 40 to about 210 of SEQ ID NO:2; and    (e) amino acids from about 40 to about 177 of SEQ ID NO:2.    
     
     
         54 . The isolated polypeptide of  claim 52  comprising amino acids selected from the group consisting of: 
 (a) amino acids from about 1 to about 210 of SEQ ID NO:2;    (b) amino acids from about 2 to about 210 of SEQ ID NO:2;    (c) amino acids from about 1 to about 177 of SEQ ID NO:2;    (d) amino acids from about 40 to about 210 of SEQ ID NO:2; and    (e) amino acids from about 40 to about 177 of SEQ ID NO:2.    
     
     
         55 . An epitope-bearing portion of the polypeptide of SEQ ID NO:2.  
     
     
         56 . The epitope-bearing portion of  claim 55 , which comprises between 10 and 50 contiguous amino acids of SEQ ID NO:2.  
     
     
         57 . An isolated antibody that binds specifically to the polypeptide of  claim 52 .  
     
     
         58 . An isolated antibody that binds specifically to the polypeptide of  claim 53 .  
     
     
         59 . An isolated antibody that binds specifically to the polypeptide of  claim 54.