Combination PDGF, KGF, IGF, and IGFBP for wound healing

Abstract

The invention provides a therapeutic composition for epithelial wound repair that is a combination of PDGF and KGF. Further, the invention provides a composition for epithelial wound repair that is a therapeutic combination of PDGF, KGF, and IGF. Additionally, the invention provides a therapeutic composition of PDGF, KGF, IGF and IGFBP for epithelial wound repair.

1 . A pharmaceutical composition for repair of epithelial tissues comprising a first polypeptide having the biological activity of a platelet derived growth factor (PDGF) and a second polypeptide having the biological activity of keratinocyte growth factor (KGF).  
   
   
       2 . The pharmaceutical composition of  claim 1 , wherein the first polypeptide comprises a full-length PDGF polypeptide.  
   
   
       3 . The pharmaceutical composition of  claim 1 , wherein the first polypeptide comprises a biologically active fragment of a full-length PDGF polypeptide.  
   
   
       4 . The pharmaceutical composition of  claim 1 , wherein the first polypeptide comprises one selected from the group consisting of PDGF A chain and PDGF B chain.  
   
   
       5 . The pharmaceutical composition of  claim 1 , wherein the first polypeptide is produced by expression of a DNA molecule that encodes PDGF in a host cell, wherein the host cell comprises one selected from the group consisting of a bacterial cell, a yeast cell, a mammalian cell, and an insect cell.  
   
   
       6 . The pharmaceutical composition of  claim 1 , wherein the second polypeptide compriese a full-length KGF.  
   
   
       7 . The pharmaceutical composition of  claim 1 , wherein the second polypeptide comprises a biologically active fragment of a full-length KGF polypeptide.  
   
   
       8 . The pharmaceutical composition of  claim 1 , wherein the second polypeptide is produced by expression of a DNA molecule that encodes KGF in a host cell, wherein the host cell comprises one selected from the group consisting of a bacterial cell, a yeast cell, a mammalian cell, and an insect cell.  
   
   
       9 . The pharmaceutical composition of  claim 1 , further comprising a pharmaceutically acceptable carrier.  
   
   
       10 . A method of repairing epithelial tissues comprising applying to the tissue to be repaired the pharmaceutical composition of  claim 1 .  
   
   
       11 . The method of  claim 10 , wherein the epithelial tissue is selected from the group consisting of skin, gastric lining, and intestinal lining.  
   
   
       12 . The method of  claim 10 , wherein the pharmaceutical composition is applied in the manner selected from the group consisting of locally, orally, intradermally, subcutaneously, intraluminally, intragastrically, and intraperitoneally.  
   
   
       13 . A method of repairing or preventing epithelial cell damage comprising applying to the cells to be protected or repaired a pharmaceutical composition comprising PDGF and a composition comprising KGF.  
   
   
       14 . The method of  claim 13 , wherein the pharmaceutical composition comprising PDGF and the pharmaceutical composition KGF are the same pharmaceutical composition.  
   
   
       15 . The method of  claim 13 , wherein application of PDGF and KGF is contemporaneous.  
   
   
       16 - 24 . (canceled)  
   
   
       25 . The pharmaceutical composition of  claim 1 , also comprising a third polynucleotide having the biological activity of insulin-like growth factor (IGF).  
   
   
       26 . The pharmaceutical composition of  claim 25 , wherein IGF comprises one selected from the group consisting of IGF-1 and IGF-2.  
   
   
       27 . The pharmaceutical composition of  claim 25 , also comprising a fourth polynucleotide having the biological activity of insulin-like growth factor binding protein (IGFBP).  
   
   
       28 . The pharmaceutical composition of  claim 27 , wherein the IGFBP comprises one selected from the group consisting of IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-5, and IGFBP-6.  
   
   
       29 . The pharmaceutical composition of  claim 25  wherein the third polypeptide comprises full-length IGF.  
   
   
       30 . The pharmaceutical composition of  claim 25  wherein the third polypeptide comprises a biologically active fragment of IGF.  
   
   
       31 . The pharmaceutical composition of  claim 27  wherein the fourth polypeptide comprises a full-length IGFBP.  
   
   
       32 . The pharmaceutical composition of  claim 27  wherein the fourth polypeptide comprises a biologically active fragment of an IGFBP.  
   
   
       33 . The pharmaceutical composition of  claim 25  wherein the third polypeptide is produced by expression of a DNA molecule that encodes IGF in a host cell, wherein the host cell comprises one selected from the group consisting of a bacterial cell, a yeast cell, a mammalian cell, and an insect cell.  
   
   
       34 . The pharmaceutical composition of  claim 27  wherein the fourth polypeptide is produced by expression of a DNA molecule that encodes an IGFBP in a host cell, wherein the host cell comprises one selected from the group consisting of a bacterial cell, a yeast cell, a mammalian cell, and an insect cell.  
   
   
       35 . The pharmaceutical composition of  claim 25  further comprising a pharmaceutically acceptable carrier.  
   
   
       36 . The pharmaceutical composition of  claim 27  further comprising a pharmaceutically acceptable carrier.  
   
   
       37 . A method of repairing epithelial tissues comprising applying to the tissue to be repaired the pharmaceutical composition of  claim 25 .  
   
   
       38 . A method of repairing epithelial tissues comprising applying to the tissue to be repaired the pharmaceutical composition of  claim 27 .  
   
   
       39 . The method of  claim 38 , wherein the epithelial tissue comprises one selected from the group consisting of skin, gastric lining, and intestinal lining.  
   
   
       40 . The method of  claim 38 , wherein the epithelial tissue comprises one selected from the group consisting of skin, gastric lining, and intestinal lining.  
   
   
       41 . The method of  claim 39 , wherein the pharmaceutical composition is applied in a manner selected from the group consisting of locally, orally, intradermally, subcutaneously, intraluminally, intragastrically, and intraperitoneally.  
   
   
       42 . The method of  claim 40 , wherein the pharmaceutical composition is applied in a manner selected from the group consisting of locally, orally, intradermally, subcutaneously, intraluminally, intragastrically, and intraperitoneally.  
   
   
       43 . A method of repairing or preventing epithelial cell damage comprising applying to the cells to be protected or repaired the pharmaceutical composition of  claim 13  and further comprising a composition comprising IGF.  
   
   
       44 . A method of repairing or preventing epithelial cell damage comprising applying to the cells to be protected or repaired the pharmaceutical composition of  claim 43  and further comprising a composition comprising an IGFBP.  
   
   
       45 - 48 . (canceled)  
   
   
       49 . The pharmaceutical composition of  claim 1 , comprising one selected from the group consisting of a cream, a foam, an injectable solution, a spray, a gel matrix, a sponge, drops, and a wash.  
   
   
       50 . The pharmaceutical composition of  claim 25 , comprising one selected from the group consisting of a cream, a foam, an injectable solution, a spray, a gel matrix, a sponge, drops, and a wash.  
   
   
       51 . The pharmaceutical composition of  claim 27 , comprising one selected from the group consisting of a cream, a foam, an injectable solution, a spray, a gel matrix, a sponge, drops, and a wash.