US2015250699A1PendingUtilityA1

Trpv3 agonists for the treatment of skin conditions

Individually held — no corporate assignee on recordPriority: Sep 14, 2012Filed: Sep 16, 2013Published: Sep 10, 2015
Est. expirySep 14, 2032(~6.1 yrs left)· nominal 20-yr term from priority
Inventors:John M. Stewart
A61P 17/00A61P 17/02C07K 14/47A61K 38/1709A61K 8/64A61Q 19/00A61K 38/17A61K 38/10C07K 14/4747A61Q 19/08A61K 38/08C07K 7/06
57
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Claims

Abstract

Described are methods and uses of TRPV3 agonists for the treatment of conditions associated with TRPV3 pathophysiology such as acne, psoriasis, dermatitis, would healing, the inhibition of hair growth, anxiety or depression. Peptides comprising all or part of the C-terminal portion of soricidin are shown to activate TRPV3 cation channel activity and/or promote wound healing in keratinocytes.

Claims

exact text as granted — not AI-modified
1 . Use of a peptide comprising between 5 and 27 contiguous amino acid residues of the amino acid sequence EGKLSSNDTEGGLCKEFLHPSKVDLPR (SEQ ID NO:1) to promote tissue repair in a subject in need thereof. 
     
     
         2 . The use of  claim 1 , wherein the tissue is skin tissue. 
     
     
         3 . The use of  claim 1 , wherein the tissue is nerve tissue. 
     
     
         4 . The use of any one of  claims 1  to  3 , for treating a wound in the subject. 
     
     
         5 . The use of  claim 4 , wherein the wound is a cut, abrasion, laceration, fissure, puncture wound, or contusion. 
     
     
         6 . The use of  claim 4 , wherein the wound is a surgical wound. 
     
     
         7 . The use of  claim 4 , wherein the wound is a thermal wound. 
     
     
         8 . The use of  claim 4 , wherein the wound is a chemical wound. 
     
     
         9 . The use of any one of  claims 1  to  3 , for the treatment of a skin disease in the subject. 
     
     
         10 . The use of  claim 9 , wherein the skin disease comprises acne, psoriasis, dermatitis, hirsutism or a condition associated with low levels or activity of TRPV3 in the subject. 
     
     
         11 . The use of  claim 1  or  2 , for exfoliating, removing the presence of dead skin and/or increasing the rate of new skin formation. 
     
     
         12 . The use of  claim 1  or  2 , for reducing the signs of skin aging in the subject. 
     
     
         13 . The use of  claim 1  or  2 , for improving the look and/or feel of skin tissue in the subject. 
     
     
         14 . The use of any one of  claims 1  to  13 , wherein the peptide is a TRPV3 agonist. 
     
     
         15 . The use of any one of  claims 1  to  14 , wherein the peptide promotes the migration and/or proliferation of keratinocytes. 
     
     
         16 . The use of any one of  claims 1  to  15 , wherein the peptide comprises an amino acid sequence with at least 80% sequence identity to an amino acid sequence selected from EGKLSSNDTEGGLCKEFLHPSKVDLPR (SEQ ID NO:1), KEFLHPSKVDLPR (SEQ ID NO: 2), FLHPSKVDLPR (SEQ ID NO: 3), HPSKVDLPR (SEQ ID NO: 4), SKVDLPR (SEQ ID NO: 5), KVDLPR (SEQ ID NO: 6), VDLPR (SEQ ID NO: 7), FLHPSKVDL (SEQ ID NO: 8), FLHPSKV (SEQ ID NO: 9) and FLHPS (SEQ ID NO: 10). 
     
     
         17 . The use of  claim 16 , wherein the peptide comprises an amino acid sequence with at least 90% sequence identity to an amino acid sequence selected from EGKLSSNDTEGGLCKEFLHPSKVDLPR (SEQ ID NO:1), KEFLHPSKVDLPR (SEQ ID NO: 2), FLHPSKVDLPR (SEQ ID NO: 3), HPSKVDLPR (SEQ ID NO: 4), SKVDLPR (SEQ ID NO: 5), KVDLPR (SEQ ID NO: 6), VDLPR (SEQ ID NO: 7), FLHPSKVDL (SEQ ID NO: 8), FLHPSKV (SEQ ID NO: 9) and FLHPS (SEQ ID NO: 10). 
     
     
         18 . The use of  claim 17 , wherein the peptide comprises an amino acid sequence selected from EGKLSSNDTEGGLCKEFLHPSKVDLPR (SEQ ID NO:1), KEFLHPSKVDLPR (SEQ ID NO: 2), FLHPSKVDLPR (SEQ ID NO: 3), HPSKVDLPR (SEQ ID NO: 4), SKVDLPR (SEQ ID NO: 5), KVDLPR (SEQ ID NO: 6), VDLPR (SEQ ID NO: 7), FLHPSKVDL (SEQ ID NO: 8), FLHPSKV (SEQ ID NO: 9) and FLHPS (SEQ ID NO: 10). 
     
     
         19 . The use of  claim 18 , wherein the peptide consists of an amino acid sequence selected from EGKLSSNDTEGGLCKEFLHPSKVDLPR (SEQ ID NO:1), KEFLHPSKVDLPR (SEQ ID NO: 2), FLHPSKVDLPR (SEQ ID NO: 3), HPSKVDLPR (SEQ ID NO: 4), SKVDLPR (SEQ ID NO: 5), KVDLPR (SEQ ID NO: 6), VDLPR (SEQ ID NO: 7), FLHPSKVDL (SEQ ID NO: 8), FLHPSKV (SEQ ID NO: 9) and FLHPS (SEQ ID NO: 10). 
     
     
         20 . The use of any one of  claims 1  to  19 , wherein the peptide comprises between 5 and 11 contiguous amino acids of KEFLHPSKVDLPR (SEQ ID NO: 2). 
     
     
         21 . The use of  claim 20 , wherein the peptide consists of between 5 and 11 contiguous amino acids of KEFLHPSKVDLPR (SEQ ID NO: 2). 
     
     
         22 . The use of any one of  claims 1  to  22 , wherein the peptide consists of 30 or fewer, 27 or fewer, 25 or fewer, 20 or fewer, 15 or fewer, 13 or fewer, 11 or fewer, 9 or fewer, or 7 or fewer amino acids. 
     
     
         23 . The use of any one of  claims 1  to  23 , wherein the peptide does not have paralytic activity. 
     
     
         24 . The use of any one of  claims 1  to  23 , wherein the peptide is formulated for topical use. 
     
     
         25 . The use of any one of  claims 1  to  24 , wherein the peptide consists of between 5 and 9 contiguous amino acids of HPSKVDLPR (SEQ ID NO: 4). 
     
     
         26 . A method for activating TRPV3 cation channel activity in a cell comprising contacting the cell with a peptide comprising between 5 and 27 contiguous amino acids of the amino acid sequence EGKLSSNDTEGGLCKEFLHPSKVDLPR (SEQ ID NO:1). 
     
     
         27 . The method of  claim 26 , wherein the cell is a keratinocyte. 
     
     
         28 . The method of  claim 26 , wherein the cell is a neuron. 
     
     
         29 . The method of any one of  claims 26  to  28 , wherein the cell is in vitro, in vivo or ex vivo. 
     
     
         30 . The method of any one of  claims 26  to  29 , wherein activating TRPV3 cation channel activity in the cell promotes migration and/or proliferation of the cell. 
     
     
         31 . The method of any one of  claims 26  to  29 , wherein activating TRPV3 cation channel activity in the cell causes death of the cell. 
     
     
         32 . The method of any one of  claims 26  to  31 , wherein the peptide comprises an amino acid sequence with at least 80% sequence identity to an amino acid sequence selected from EGKLSSNDTEGGLCKEFLHPSKVDLPR (SEQ ID NO:1), KEFLHPSKVDLPR (SEQ ID NO: 2), FLHPSKVDLPR (SEQ ID NO: 3), HPSKVDLPR (SEQ ID NO: 4), SKVDLPR (SEQ ID NO: 5), KVDLPR (SEQ ID NO: 6), VDLPR (SEQ ID NO: 7), FLHPSKVDL (SEQ ID NO: 8), FLHPSKV (SEQ ID NO: 9) and FLHPS (SEQ ID NO: 10). 
     
     
         33 . The method of  claim 32 , wherein the peptide comprises an amino acid sequence with at least 90% sequence identity to an amino acid sequence selected from EGKLSSNDTEGGLCKEFLHPSKVDLPR (SEQ ID NO:1), KEFLHPSKVDLPR (SEQ ID NO: 2), FLHPSKVDLPR (SEQ ID NO: 3), HPSKVDLPR (SEQ ID NO: 4), SKVDLPR (SEQ ID NO: 5), KVDLPR (SEQ ID NO: 6), VDLPR (SEQ ID NO: 7), FLHPSKVDL (SEQ ID NO: 8), FLHPSKV (SEQ ID NO: 9) and FLHPS (SEQ ID NO: 10). 
     
     
         34 . The method of  claim 33 , wherein the peptide comprises an amino acid sequence selected from EGKLSSNDTEGGLCKEFLHPSKVDLPR (SEQ ID NO:1), KEFLHPSKVDLPR (SEQ ID NO: 2), FLHPSKVDLPR (SEQ ID NO: 3), HPSKVDLPR (SEQ ID NO: 4), SKVDLPR (SEQ ID NO: 5), KVDLPR (SEQ ID NO: 6), VDLPR (SEQ ID NO: 7), FLHPSKVDL (SEQ ID NO: 8), FLHPSKV (SEQ ID NO: 9) and FLHPS (SEQ ID NO: 10). 
     
     
         35 . The method of  claim 34 , wherein the peptide consists of an amino acid sequence selected from EGKLSSNDTEGGLCKEFLHPSKVDLPR (SEQ ID NO:1), KEFLHPSKVDLPR (SEQ ID NO: 2), FLHPSKVDLPR (SEQ ID NO: 3 HPSKVDLPR (SEQ ID NO: 4), SKVDLPR (SEQ ID NO: 5), KVDLPR (SEQ ID NO: 6), VDLPR (SEQ ID NO: 7), FLHPSKVDL (SEQ ID NO: 8), FLHPSKV (SEQ ID NO: 9) and FLHPS (SEQ ID NO: 10). 
     
     
         36 . The method of any one of  claims 26  to  35 , wherein the peptide comprises between 5 and 11 contiguous amino acids of KEFLHPSKVDLPR (SEQ ID NO: 2). 
     
     
         37 . The method of  claim 36 , wherein the peptide consists of between 5 and 11 contiguous amino acids of KEFLHPSKVDLPR (SEQ ID NO: 2). 
     
     
         38 . The method of any one of  claims 26  to  37 , wherein the peptide consists of 30 or fewer, 27 or fewer, 25 or fewer, 20 or fewer, 15 or fewer, 13 or fewer, 11 or fewer, 9 or fewer, or 7 or fewer amino acids. 
     
     
         39 . The method of any one of  claims 26  to  38 , wherein the peptide does not have paralytic activity. 
     
     
         40 . The method of any one of  claims 26  to  38 , wherein the peptide consists of between 5 and 9 contiguous amino acids of HPSKVDLPR (SEQ ID NO: 4). 
     
     
         41 . A method of treating a subject to promote tissue repair comprising administering to the subject a peptide comprising between 5 and 27 contiguous amino acid residues of the amino acid sequence EGKLSSNDTEGGLCKEFLHPSKVDLPR (SEQ ID NO:1). 
     
     
         42 . The method of  claim 1 , wherein the tissue is skin tissue. 
     
     
         43 . The method of  claim 1 , wherein the tissue is nerve tissue. 
     
     
         44 . The method of any one of  claims 41  to  43 , for treating a wound in the subject. 
     
     
         45 . The method of  claim 44 , wherein the wound is a cut, abrasion, laceration, fissure, puncture wound or contusion. 
     
     
         46 . The method of  claim 44 , wherein the wound is a surgical wound. 
     
     
         47 . The method of  claim 44 , wherein the wound is a thermal wound. 
     
     
         48 . The method of  claim 44 , wherein the wound is a chemical wound. 
     
     
         49 . The method of any one of  claims 41  to  43 , for the treatment of a skin disease in the subject. 
     
     
         50 . The method of  claim 49 , wherein the skin disease comprises acne, psoriasis, dermatitis, hirsutism or a condition associated with low levels or activity of TRPV3 in the subject. 
     
     
         51 . The method of  claim 41  or  42 , for exfoliating, removing the presence of dead skin and/or increasing the rate of new skin formation. 
     
     
         52 . The method of  claim 41  or  42 , for reducing the signs of skin aging in the subject. 
     
     
         53 . The method of  claim 41  or  42 , for improving the look and/or feel of skin tissue in the subject. 
     
     
         54 . The method of any one of  claims 41  to  53 , wherein the peptide is a TRPV3 agonist. 
     
     
         55 . The method of any one of  claims 41  to  54 , wherein the peptide promotes the migration and/or proliferation of keratinocytes. 
     
     
         56 . The method of any one of  claims 41  to  55 , wherein the peptide comprises an amino acid sequence with at least 80% sequence identity to an amino acid sequence selected from EGKLSSNDTEGGLCKEFLHPSKVDLPR (SEQ ID NO:1), KEFLHPSKVDLPR (SEQ ID NO: 2), FLHPSKVDLPR (SEQ ID NO: 3), HPSKVDLPR (SEQ ID NO: 4), SKVDLPR (SEQ ID NO: 5), KVDLPR (SEQ ID NO: 6), VDLPR (SEQ ID NO: 7), FLHPSKVDL (SEQ ID NO: 8), FLHPSKV (SEQ ID NO: 9) and FLHPS (SEQ ID NO: 10). 
     
     
         57 . The method of  claim 56 , wherein the peptide comprises an amino acid sequence with at least 90% sequence identity to an amino acid sequence selected from EGKLSSNDTEGGLCKEFLHPSKVDLPR (SEQ ID NO:1), KEFLHPSKVDLPR (SEQ ID NO: 2), FLHPSKVDLPR (SEQ ID NO: 3), HPSKVDLPR (SEQ ID NO: 4), SKVDLPR (SEQ ID NO: 5), KVDLPR (SEQ ID NO: 6), VDLPR (SEQ ID NO: 7), FLHPSKVDL (SEQ ID NO: 8), FLHPSKV (SEQ ID NO: 9) and FLHPS (SEQ ID NO: 10). 
     
     
         58 . The method of  claim 57 , wherein the peptide comprises an amino acid sequence selected from EGKLSSNDTEGGLCKEFLHPSKVDLPR (SEQ ID NO:1), KEFLHPSKVDLPR (SEQ ID NO: 2), FLHPSKVDLPR (SEQ ID NO: 3), HPSKVDLPR (SEQ ID NO: 4), SKVDLPR (SEQ ID NO: 5), KVDLPR (SEQ ID NO: 6), VDLPR (SEQ ID NO: 7), FLHPSKVDL (SEQ ID NO: 8), FLHPSKV (SEQ ID NO: 9) and FLHPS (SEQ ID NO: 10). 
     
     
         59 . The method of  claim 58 , wherein the peptide consists of an amino acid sequence selected from EGKLSSNDTEGGLCKEFLHPSKVDLPR (SEQ ID NO:1), KEFLHPSKVDLPR (SEQ ID NO: 2), FLHPSKVDLPR (SEQ ID NO: 3 HPSKVDLPR (SEQ ID NO: 4), SKVDLPR (SEQ ID NO: 5), KVDLPR (SEQ ID NO: 6), VDLPR (SEQ ID NO: 7), FLHPSKVDL (SEQ ID NO: 8), FLHPSKV (SEQ ID NO: 9) and FLHPS (SEQ ID NO: 10). 
     
     
         60 . The method of any one of  claims 41  to  59 , wherein the peptide comprises between 5 and 11 contiguous amino acids of KEFLHPSKVDLPR (SEQ ID NO: 2). 
     
     
         61 . The method of  claim 60 , wherein the peptide consists of between 5 and 11 contiguous amino acids of KEFLHPSKVDLPR (SEQ ID NO: 2). 
     
     
         62 . The method any one of  claims 41  to  61 , wherein the peptide consists of fewer than 30, fewer than 25, fewer than 20, fewer than 15, fewer than 13, fewer than 11, fewer than 9 amino acids or fewer than 7 amino acids. 
     
     
         63 . The method of any one of  claims 41  to  62 , wherein the peptide does not have paralytic activity. 
     
     
         64 . The method of any one of  claims 41  to  63 , wherein the peptide is administered as a topical formulation. 
     
     
         65 . The method of any one of  claims 41  to  64 , wherein the peptide consists of between 5 and 9 contiguous amino acids of HPSKVDLPR (SEQ ID NO: 4). 
     
     
         66 . A peptide comprising an amino acid sequence consisting of between 5 and 11 contiguous amino acids of SEQ ID NO: 2. 
     
     
         67 . The peptide of  claim 66 , wherein the peptide comprises a sequence with at least 80% sequence identity to an amino acid sequence selected from FLHPSKVDLPR (SEQ ID NO: 3), HPSKVDLPR (SEQ ID NO: 4), SKVDLPR (SEQ ID NO: 5), KVDLPR (SEQ ID NO: 6), VDLPR (SEQ ID NO: 7), FLHPSKVDL (SEQ ID NO: 8), FLHPSKV (SEQ ID NO: 9) and FLHPS (SEQ ID NO: 10). 
     
     
         68 . The peptide of  claim 67 , wherein the peptide comprises an amino acid sequence selected from FLHPSKVDLPR (SEQ ID NO: 3), HPSKVDLPR (SEQ ID NO: 4), SKVDLPR (SEQ ID NO: 5), KVDLPR (SEQ ID NO: 6), VDLPR (SEQ ID NO: 7), FLHPSKVDL (SEQ ID NO: 8), FLHPSKV (SEQ ID NO: 9) and FLHPS (SEQ ID NO: 10). 
     
     
         69 . The peptide of any one of  claims 66  to  68 , wherein the peptide consists of between 5 and 11 contiguous amino acids of SEQ ID NO: 2. 
     
     
         70 . The peptide of any one of  claims 66  to  68 , wherein the peptide consists of 9 or fewer amino acids. 
     
     
         71 . The peptide of any one  claims 66  to  68 , wherein the peptide consists of 7 or fewer amino acids. 
     
     
         72 . The peptide of any one of  claims 66  to  68 , wherein the peptide consists of a sequence selected from FLHPSKVDLPR (SEQ ID NO: 3) HPSKVDLPR (SEQ ID NO: 4), SKVDLPR (SEQ ID NO: 5), KVDLPR (SEQ ID NO: 6), VDLPR (SEQ ID NO: 7), FLHPSKVDL (SEQ ID NO: 8), FLHPSKV (SEQ ID NO: 9) and FLHPS (SEQ ID NO: 10). 
     
     
         73 . The peptide of any one of  claims 66  to  72 , wherein the peptide is a TRPV3 agonist. 
     
     
         74 . The peptide of any one of  claims 66  to  73 , wherein the peptide promotes the migration and/or proliferation of keratinocytes. 
     
     
         75 . The peptide of  claim 66 , wherein the peptide comprises at least 7 contiguous amino acids of the amino acid sequence HPSKVDLPR (SEQ ID NO: 4). 
     
     
         76 . The peptide of  claim 75 , wherein the peptide consists of at least 7 contiguous amino acids of HPSKVDLPR (SEQ ID NO: 4). 
     
     
         77 . The peptide of  claim 75  or  76 , wherein the peptide causes cell death. 
     
     
         78 . The peptide of  claim 66 , wherein the peptide comprises at least 5 contiguous amino acids of FLHPSKVDL (SEQ ID NO: 8). 
     
     
         79 . The peptide of  claim 78 , wherein the peptide consists of at least 5 contiguous amino acids of FLHPSKVDL (SEQ ID NO: 8). 
     
     
         80 . The peptide of  claim 66 , wherein the peptide comprises the amino acid sequence KVDLPR (SEQ ID NO: 6) or VDLPR (SEQ ID NO: 7). 
     
     
         81 . The peptide of  claim 80 , wherein the peptide consists of the amino acid sequence KVDLPR (SEQ ID NO: 6) or VDLPR (SEQ ID NO: 7). 
     
     
         82 . The peptide of any one of  claims 78  to  81 , wherein the peptide promotes the migration and/or proliferation of keratinocytes. 
     
     
         83 . The peptide of any one of  claims 66  to  82 , for use in the treatment of a skin condition. 
     
     
         84 . The peptide of any one of  claims 66  to  82 , for use in promoting tissue repair in a subject in need thereof. 
     
     
         85 . The peptide of  claim 84  for treating a wound or a skin disease in the subject. 
     
     
         86 . A composition comprising the peptide of any one of  claims 66  to  85  and a pharmaceutically or cosmetically acceptable carrier. 
     
     
         87 . The composition of  claim 86 , wherein the composition is formulated for topical use.

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