Uses of keratinocyte growth factor-2

Abstract

The present invention concerns variants and chemical derivatives of keratinocyte growth factor-2 (KGF-2) protein. Also disclosed are nucleic acid molecules encoding such a variants, as well as methods for using such variants and chemical derivatives to stimulate epithelial cell proliferation.

What is claimed is:  
     
         1 . A keratinocyte growth factor-2 (KGF-2) protein consisting of: 
 (a) residues 69 through 208 of the amino acid sequence set forth in SEQ ID NO: 2; or    (b) residues 69 through 208 of the amino sequence set forth in SEQ ID NO: 2 and an N-terminal methionine.    
     
     
         2 . The KGF-2 protein of  claim 1 , wherein the amino acid sequence is nonglycosylated.  
     
     
         3 . The KGF-2 protein of  claim 1 , wherein the amino acid sequence is glycosylated.  
     
     
         4 . A chemical derivative comprising a water-soluble polymer conjugated to the KGF-2 protein of  claim 1 .  
     
     
         5 . A polynucleotide encoding the KGF-2 protein of  claim 1 .  
     
     
         6 . A vector comprising a polynucleotide of  claim 5 , operatively linked to an expression control sequence  
     
     
         7 . A prokaryotic or eukaryotic host cell comprising the polynucleotide of  claim 5 .  
     
     
         8 . A method comprising culturing the host cell of  claim 7  in a suitable nutrient medium.  
     
     
         9 . The method of  claim 8 , wherein the host cell is an  E. coli  cell.  
     
     
         10 . The method of  claim 8 , wherein the host cell is a baculovirus cell, COS cell, or Chinese hamster ovary cell.  
     
     
         11 . A method comprising isolating a keratinocyte growth factor-2 (KGF-2) protein from a host cell comprising the polynucleotide of  claim 5 , cultured under conditions allowing the expression of the KGF-2 protein by the host cell.  
     
     
         12 . The method of  claim 11 , further comprising modifying the isolated KGF-2 protein to generate a compound capable of stimulating the production of epithelial cells.  
     
     
         13 . A method comprising: 
 (a) culturing a prokaryotic or eukaryotic host cell comprising the polynucleotide of  claim 5;  and    (b) maintaining the host cell under conditions allowing the expression of a keratinocyte growth factor-2 (KGF-2) protein by the host cell.    
     
     
         14 . The method of  claim 13 , further comprising after step (b) the following step (c): 
 (c) isolating the KGF-2 protein expressed by the host cell.    
     
     
         15 . A pharmaceutical composition comprising a keratinocyte growth factor-2 (KGF-2) protein isolated in accordance with the method of  claim 14 , in association with a pharmaceutically acceptable vehicle.  
     
     
         16 . The KGF-2 protein of  claim 1  that is the recombinant expression product of a prokaryotic or eukaryotic host cell comprising an exogenous polynucleotide of  claim 5 .  
     
     
         17 . A pharmaceutical composition comprising the KGF-2 protein of  claim 1  in association with a pharmaceutically acceptable vehicle.  
     
     
         18 . The method of claims  8 ,  9 , or  10 , further comprising isolating a keratinocyte growth factor-2 (KGF-2) protein from the cultured cells or nutrient medium.  
     
     
         19 . A pharmaceutical composition comprising a keratinocyte growth factor-2 (KGF-2) protein isolated in accordance with the method of  claim 18 , in association with a pharmaceutically acceptable vehicle.  
     
     
         20 . The KGF-2 protein of  claim 1 , wherein at least one domain of the constant region of the heavy chain of human immunoglobulin is fused to the C-terminal end of the KGF-2 protein.