Polypeptides and methods of use

Abstract

Described herein are fragments of fibronectin and vitronectin and variants thereof that have certain activities, including growth factor-binding activity. Also described are fragments of growth factors that bind to fibronectin and inhibit binding of full-length growth factors to fibronectin. Compositions containing such fragments are useful in cosmetic treatments (e.g., the treatment of wrinkles or UV photodamage of skin), and the treatment of wounds and cancer.

1 .- 81 . (canceled) 
     
     
         82 . A pharmaceutical composition comprising an isolated polypeptide consisting of an amino acid sequence conforming to the formula 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 56) 
                 
                     
                   Xaa 1 (Xaa 2 ) m -Xaa 3 -Xaa 4 -Xaa 5 -Xaa 6 -Xaa 7  (Formula IV) 
                 
             
                
                
               
            
           
         
         wherein the formula optionally includes, at an N-terminus, C-terminus, or both N- and C-termini of the polypeptide, 1-4 cysteine residues; 
         wherein Xaa 1  is Pro, Xaa 2  is any amino acid residue, m is the integer 8, Xaa 3  is Lys or Arg, Xaa 4  is any amino acid residue, Xaa 5  is Lys or Arg, and Xaa 6  is any amino acid residue; and 
         wherein the composition is formulated for intravenous administration. 
       
     
     
         83 . The pharmaceutical composition of  claim 82 , further comprising a sterile diluent, an antibacterial agent, an antioxidant, or a chelating agent. 
     
     
         84 . The pharmaceutical composition of  claim 83 , wherein the sterile diluent comprises water, a saline solution, a fixed oil, polyethylene glycol, glycerine, propylene glycol, or a synthetic solvent; the antibacterial agent is benzyl alcohol or methylparaben; the antioxidant is ascorbic acid or sodium bisulfite; and the chelating agent is ethylenediaminetetraacetic acid. 
     
     
         85 . The pharmaceutical composition of  claim 83 , wherein the composition is packaged in an ampule, a disposable syringe, or a single or multiple dose vial. 
     
     
         86 . The pharmaceutical composition of  claim 83 , wherein the composition is packaged with instructions for use. 
     
     
         87 . The pharmaceutical composition of  claim 83 , wherein the polypeptide is cyclic. 
     
     
         88 . The pharmaceutical composition of  claim 83 , wherein the polypeptide consists of the sequence PSHISKYILRWRPK (SEQ ID NO:9), PSLAKKQRFRHRNR (SEQ ID NO:10), CPSHISKYILRWRPKC (SEQ ID NO:82), or CPSLAKKQRFRHRNRC (SEQ ID NO:83). 
     
     
         89 . A method of improving the appearance of the skin, the method comprising administering to a subject an effective amount of a composition comprising an isolated polypeptide consisting of an amino acid sequence conforming to the formula 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 56) 
                 
                     
                   Xaa 1 (Xaa 2 ) m -Xaa 3 -Xaa 4 -Xaa 5 -Xaa 6 -Xaa 7  (Formula IV) 
                 
             
                
                
               
            
           
         
         wherein the formula optionally includes, at an N-terminus, C-terminus, or both N- and C-termini of the polypeptide, 1-4 cysteine residues; 
         wherein Xaa 1  is Pro, Xaa 2  is any amino acid residue, m is an integer between 0 and 8, Xaa 3  is Lys or Arg, Xaa 4  is any amino acid residue, Xaa 5  is Lys or Arg, and Xaa 6  is any amino acid residue; and 
         wherein the composition is formulated for topical administration. 
       
     
     
         90 . The method of  claim 89 , further comprising a step of identifying a subject in need of treatment. 
     
     
         91 . The method of  claim 90 , wherein the subject exhibits a visible sign of aging. 
     
     
         92 . The method of  claim 91 , wherein the visible sign of aging is a wrinkle, a dullness of the skin, a sagging appearance to the skin, or a creped appearance to the skin. 
     
     
         93 . The method of  claim 89 , wherein the composition is formulated as a cosmetic, moisturizer, sunscreen, soap, foaming cleanser, gel or cream. 
     
     
         94 . The method of  claim 89 , wherein the polypeptide is carried by a cosmetic vector selected from the group consisting of a macrocapsule, a microcapsule, a nanocapsule, a liposome, a chylomicron, a macroparticule, a microparticle, a nanoparticle, or a microsponge or adsorbed on a powdered organic polymer, talc, or bentonite. 
     
     
         95 . The method of  claim 89 , wherein the polypeptide is cyclic. 
     
     
         96 . The method of  claim 89 , wherein the polypeptide consists of the sequence PSHISKYILRWRPK (SEQ ID NO:9), PSLAKKQRFRHRNR (SEQ ID NO:10), CPSHISKYILRWRPKC (SEQ ID NO:82), or CPSLAKKQRFRHRNRC (SEQ ID NO:83).