KGF polypeptide compositions

Abstract

Compositions comprising keratinocyte growth factor (KGF) polypeptides and methods of using the same are described. The KGF polypeptides of the present invention display enhanced bioactivity relative to full-length KGF 163 . Accordingly, the KGF polypeptides of the present invention may be used in compositions in lesser amounts than would be necessary using KGF 163 .

1 . A composition comprising:
 (a) a therapeutically effective amount of a KGF polypeptide, wherein said KGF polypeptide is selected from the group consisting of:
 (i) KGF des1-22  consisting of the contiguous amino acid sequence depicted at amino acid residues 23-163, inclusive, of SEQ ID NO:26; 
 (ii) a biologically active analog of (i), wherein said biologically active analog consists of the contiguous amino acid sequence depicted at amino acid residues 23-163, inclusive, of SEQ ID NO:26 with up to 7 amino acid substitutions; and 
 (iii) the polypeptide of (i) or (ii), consisting of the amino acid sequence of (i) or (ii), respectively, and an additional N-terminal methionine, 
   wherein said KGF polypeptide exhibits an increase in bioactivity relative to mature, full-length, KGF (KGF 163 ) as determined by the Balb/MK bioactivity assay and specifically stimulates epithelial cell proliferation, and further wherein the therapeutically effective amount is 75% or less of the amount on a per molecule basis of KGF 163  needed to elicit an equivalent therapeutic response; and   (b) a pharmaceutically acceptable excipient.   
     
     
         2 . The composition of  claim 1 , wherein said KGF polypeptide is KGF des1-22  consisting of the contiguous amino acid sequence depicted at amino acid residues 23-163, inclusive, of SEQ ID NO:26. 
     
     
         3 . The composition of  claim 1 , wherein the therapeutically effective amount is 10% to 50% of the amount on a per molecule basis of the amount of KGF 163  needed to elicit an equivalent therapeutic response. 
     
     
         4 . The composition of  claim 1 , wherein the therapeutically effective amount is 10% to 25% of the amount on a per molecule basis of the amount of KGF 163  needed to elicit an equivalent therapeutic response. 
     
     
         5 . The composition of  claim 1 , wherein the therapeutically effective amount is 10% to 20% of the amount on a per molecule basis of the amount of KGF 163  needed to elicit an equivalent therapeutic response. 
     
     
         6 . A method of stimulating epithelial cell proliferation comprising contacting epithelial cells with a composition according to  claim 1 . 
     
     
         7 . The method of  claim 6 , wherein said biologically active analog consists of the contiguous amino acid sequence depicted at amino acid residues 23-163, inclusive, of SEQ ID NO:26 with the N-terminal arginine residue substituted with an alanine residue. 
     
     
         8 . The method of  claim 6 , wherein said KGF polypeptide is KGF des1-22  consisting of the contiguous amino acid sequence depicted at amino acid residues 23-163, inclusive, of SEQ ID NO:26. 
     
     
         9 . The method of  claim 6 , wherein the therapeutically effective amount is 10% to 50% of the amount on a per molecule basis of the amount of KGF 163  needed to elicit an equivalent therapeutic response. 
     
     
         10 . The method of  claim 6 , wherein the therapeutically effective amount is 10% to 25% of the amount on a per molecule basis of the amount of KGF 163  needed to elicit an equivalent therapeutic response. 
     
     
         11 . The method of  claim 6 , wherein the therapeutically effective amount is 10% to 20% of the amount on a per molecule basis of the amount of KGF 163  needed to elicit an equivalent therapeutic response. 
     
     
         12 . The method of  claim 6 , wherein said contacting is done in vitro. 
     
     
         13 . The method of  claim 6 , wherein said contacting is done in vivo. 
     
     
         14 . A method of treating wounds comprising applying a KGF polypeptide composition according to  claim 1  to an area of a wound to be treated and allowing the wound to heal. 
     
     
         15 . The method of  claim 14 , wherein said KGF polypeptide is KGF des1-22  consisting of the contiguous amino acid sequence depicted at amino acid residues 23-163, inclusive, of SEQ ID NO:26. 
     
     
         16 . The method of  claim 14 , wherein the therapeutically effective amount is 10% to 50% of the amount on a per molecule basis of the amount of KGF 163  needed to elicit an equivalent therapeutic response. 
     
     
         17 . The method of  claim 14 , wherein the therapeutically effective amount is 10% to 25% of the amount on a per molecule basis of the amount of KGF 163  needed to elicit an equivalent therapeutic response. 
     
     
         18 . The method of  claim 14 , wherein the therapeutically effective amount is 10% to 20% of the amount on a per molecule basis of the amount of KGF 163  needed to elicit an equivalent therapeutic response. 
     
     
         19 . The method of  claim 14 , wherein said contacting is done in vitro. 
     
     
         20 . The method of  claim 14 , wherein said contacting is done in vivo.