US2007110698A1PendingUtilityA1

Regulation of epithelial tissue by hedgehog-like polypeptides, and formulations and uses related thereto

58
Individually held — no corporate assignee on recordPriority: Oct 20, 1997Filed: Jul 15, 2005Published: May 17, 2007
Est. expiryOct 20, 2017(expired)· nominal 20-yr term from priority
Inventors:Elizabeth A. Wang
A61P 35/00A61P 17/02A61P 1/02A61P 17/14A61P 17/00C07K 14/465A61K 38/1709C07K 14/43581C12N 5/0629A61K 31/496C07K 14/461A61Q 7/00A61Q 7/02A61Q 19/08A61K 8/606A61K 35/12A61Q 19/00C12N 5/0627C12N 2501/41C12N 2501/70A61K 8/64A61K 38/1703C07K 14/4702A61K 31/47A61K 48/00A61K 38/17
58
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Claims

Abstract

One aspect of the present application relates to a method for modulating the growth state of an epithelial cell by ectopically contacting the epithelial cell, in vitro or in vivo, with a hedgehog therapeutic or ptc therapeutic in an amount effective to alter the rate (promote or inhibit) of proliferation of the epithelial cell, e.g., relative to the absence of administeration of the hedgehog therapeutic or ptc therapeutic. The subject method can be used, for example, to modulate the growth state of an epithelial tissue, such as for inducing the formation of skin or other cutaneous tissue, or for inducing growth of hair.

Claims

exact text as granted — not AI-modified
1 - 68 . (canceled)  
     
     
         69 . A method for promoting wound healing, comprising administering to a mammal in need thereof an amount of an agent effective to promote wound healing of said mammal in need thereof, wherein the agent is a  hedgehog  agonist or a patched antagonist that promotes  hedgehog  signal transduction, and wherein the  hedgehog  agonist or patched antagonist promotes  hedgehog  signal transduction by a mechanism selected from 
 (i) binding to patched;    (ii) altering binding or enzymatic activity of a protein involved in  hedgehog  signal transduction; or    (iii) altering expression of a  hedgehog  protein, a patched protein, or a protein involved in  hedgehog  signal transduction.    
     
     
         70 . The method of  claim 69 , wherein the agent is a  hedgehog  agonist.  
     
     
         71 . The method of  claim 69 , wherein the agent is a patched antagonist.  
     
     
         72 . The method of  claim 69 , wherein the  hedgehog  agonist is a peptidomimetic of a  hedgehog  polypeptide sequence.  
     
     
         73 . The method of  claim 69 , wherein the  hedgehog  agonist is a polypeptide including a  hedgehog  polypeptide sequence of at least a bioactive extracellular portion of a  hedgehog  protein.  
     
     
         74 . The method of  claim 73 , wherein the polypeptide includes at least 50 contiguous amino acids residues of an N-terminal half of the  hedgehog  protein.  
     
     
         75 . The method of  claim 73 , wherein the polypeptide includes at least 100 contiguous amino acids of an extracellular domain of the  hedgehog  protein.  
     
     
         76 . The method of  claim 73 , wherein the polypeptide includes at least a 19 kd fragment of an extracellular domain of the  hedgehog  protein.  
     
     
         77 . The method of  claim 73 , wherein the  hedgehog  protein is modified with one or more lipophilic or hydrophobic moieties.  
     
     
         78 . The method of  claim 73 , wherein the  hedgehog  polypeptide is modified with one or more sterol moieties.  
     
     
         79 . The method of  claim 78 , wherein the sterol moiety is cholesterol.  
     
     
         80 . The method of  claim 77 , wherein the one or more lipophilic moieties are one or more fatty acid moieties.  
     
     
         81 . The method of  claim 80 , wherein each fatty acid moiety is independently selected from myristoyl, palmitoyl, stearoyl, or arachidoyl.  
     
     
         82 . The method of  claim 80 , wherein the  hedgehog  polypeptide is modified with one or more aromatic hydrocarbons.  
     
     
         83 . The method of  claim 69 , wherein the method promotes healing of a wound resulting from surgery, burn, inflammation, or irritation.  
     
     
         84 . The method of  claim 83 , wherein the surgery is cosmetic surgery.  
     
     
         85 . The method of  claim 69 , wherein the agent is administered as a pharmaceutical composition.  
     
     
         86 . The method of  claim 69 , wherein administering comprises contacting skin of the mammal in need thereof with a topical formulation comprising the composition.  
     
     
         87 . The method of  claim 86 , wherein the composition is formulated for topical application on a sponge, bandage, dressing, or film.  
     
     
         88 . A method for promoting wound healing, comprising contacting skin of a mammal in need thereof with a composition comprising an amount of an agent effective to promote wound healing of said mammal in need thereof, wherein the agent is a  hedgehog  agonist or a patched antagonist that promotes  hedgehog  signal transduction, and wherein the  hedgehog  agonist or patched antagonist promotes  hedgehog  signal transduction by a mechanism selected from 
 (i) binding to patched;    (ii) altering binding or enzymatic activity of a protein involved in  hedgehog  signal transduction; or    (iii) altering expression of a  hedgehog  protein, a patched protein or a protein involved in  hedgehog  signal transduction.    
     
     
         89 . The method of  claim 88 , wherein the composition is a pharmaceutical composition.  
     
     
         90 . The method of  claim 88 , wherein the composition is formulated for topical application.  
     
     
         91 . The method of  claim 90 , wherein the composition is formulated for topical application on a sponge, bandage, dressing, or film.  
     
     
         92 . The method of  claim 88 , wherein the agent is a  hedgehog  agonist.  
     
     
         93 . The method of  claim 88 , wherein the agent is a patched antagonist.  
     
     
         94 . The method of  claim 88 , wherein the  hedgehog  agonist is a peptidomimetic of a  hedgehog  polypeptide sequence.  
     
     
         95 . The method of  claim 88 , wherein the  hedgehog  agonist is a polypeptide including a  hedgehog  polypeptide sequence of at least a bioactive extracellular portion of a  hedgehog  protein.  
     
     
         96 . The method of  claim 95 , wherein the polypeptide includes at least 50 contiguous amino acids residues of an N-terminal half of the  hedgehog  protein.  
     
     
         97 . The method of  claim 95 , wherein the polypeptide includes at least 100 contiguous amino acids of an extracellular domain of the  hedgehog  protein.  
     
     
         98 . The method of  claim 95 , wherein the polypeptide includes at least a 19 kd fragment of an extracellular domain of the  hedgehog  protein.  
     
     
         99 . The method of  claim 95 , wherein the  hedgehog  protein is modified with one or more lipophilic or hydrophobic moieties.  
     
     
         100 . The method of  claim 95 , wherein the  hedgehog  polypeptide is modified with one or more sterol moieties.  
     
     
         101 . The method of  claim 100 , wherein the sterol moiety is cholesterol.  
     
     
         102 . The method of  claim 99 , wherein the one or more lipophilic moieties are one or more fatty acid moieties.  
     
     
         103 . The method of  claim 102 , wherein each fatty acid moiety is independently selected from myristoyl, palmitoyl, stearoyl, or arachidoyl.  
     
     
         104 . The method of  claim 102 , wherein the  hedgehog  polypeptide is modified with one or more aromatic hydrocarbons.  
     
     
         105 . The method of  claim 88 , wherein the method promotes healing of a wound resulting from surgery, burn, inflammation, or irritation.  
     
     
         106 . The method of  claim 105 , wherein the surgery is cosmetic surgery.  
     
     
         107 . The method of  claim 69 , wherein the method promotes wound healing with less scarring.  
     
     
         108 . The method of  claim 88 , wherein the method promotes wound healing with less scarring.  
     
     
         109 . The method of  claim 69 , wherein the method is used in conjunction with a skin graft.  
     
     
         110 . The method of  claim 88 , wherein the method is used in conjunction with a skin graft.

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