Peptides for the treatment of hearing
First Claim
Patent Images
1. A method of treating noise-induced hearing loss, the method comprising administering to a subject in need or want of relief thereof a therapeutically-effective amount of a peptide that is:
- a peptide of Formula (I) or Formula (II),
(capN)(capN)N-tranN-pepN-(X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12)x-pepC-tranC-C(O)-capC
Formula (I),
(capN)(capN)N-tranN-pepN-(X12-X11-X10-X9-X8-X7-X6-X5-X4-X3-X2-X1)x-pepC-tranC-C(O)-capC
Formula (II), whereineach capN is independently H, alkyl, aryl, aralkyl, an acyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, or an aminocarbonyl group, or both capN groups together with N form a heterocycle;
tranN and tranC are each independently a transducing sequence or absent;
pepN and pepC are each independently an amino acid sequence or absent;
X1 is A, K, an acidic amino acid residue, or is absent;
X2 is A, I, L, or V;
X3 is A, D, I, L, P, or V;
X4 is A, E, I, Y, or a basic amino acid residue;
X5 is A, I, L, or V;
X6 is A, G, S, T, or Y;
X7 is A, E, I, L, or V;
X8 is A, P, S, T, or an aromatic amino acid residue;
X9 is A, K, or an acidic amino acid residue;
X10 is A, C, M, S, α
-aminobutyric acid, or norvaline;
X11 is A, I, L, V, or is absent;
X12 is G or is absent;
x is 1, 2, or 3;
capC is OH, alkoxy, aryloxy, arylalkoxy, amino, alkylamino, dialkylamino, or a heterocycle; and
each amino acid residue side chain is independently uncapped or capped with a capping group, or a stereoisomer or pharmaceutically-acceptable salt of any of the foregoing peptides, wherein the amino acid sequence of the peptide is not SEQ ID NO;
183, SEQ ID NO;
184, SEQ ID NO;
185, SEQ ID NO;
186, SEQ ID NO;
369, or SEQ ID NO;
378.
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Accused Products
Abstract
Peptides for the treatment of inflammation, and therapeutic uses and methods of using the same are disclosed. Peptides including a transducing sequence are effective for inhibiting cytokine activity and TNF-α secretion through interaction with toll-like receptor signaling pathways. Experiments are described illustrating the efficacy of the compounds in treating otitis media, noise-induced hearing loss, age-related hearing loss, and improvement of ordinary hearing.
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Citations
102 Claims
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1. A method of treating noise-induced hearing loss, the method comprising administering to a subject in need or want of relief thereof a therapeutically-effective amount of a peptide that is:
a peptide of Formula (I) or Formula (II),
(capN)(capN)N-tranN-pepN-(X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12)x-pepC-tranC-C(O)-capC
Formula (I),
(capN)(capN)N-tranN-pepN-(X12-X11-X10-X9-X8-X7-X6-X5-X4-X3-X2-X1)x-pepC-tranC-C(O)-capC
Formula (II), whereineach capN is independently H, alkyl, aryl, aralkyl, an acyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, or an aminocarbonyl group, or both capN groups together with N form a heterocycle; tranN and tranC are each independently a transducing sequence or absent; pepN and pepC are each independently an amino acid sequence or absent; X1 is A, K, an acidic amino acid residue, or is absent; X2 is A, I, L, or V; X3 is A, D, I, L, P, or V; X4 is A, E, I, Y, or a basic amino acid residue; X5 is A, I, L, or V; X6 is A, G, S, T, or Y; X7 is A, E, I, L, or V; X8 is A, P, S, T, or an aromatic amino acid residue; X9 is A, K, or an acidic amino acid residue; X10 is A, C, M, S, α
-aminobutyric acid, or norvaline;X11 is A, I, L, V, or is absent; X12 is G or is absent; x is 1, 2, or 3; capC is OH, alkoxy, aryloxy, arylalkoxy, amino, alkylamino, dialkylamino, or a heterocycle; and
each amino acid residue side chain is independently uncapped or capped with a capping group, or a stereoisomer or pharmaceutically-acceptable salt of any of the foregoing peptides, wherein the amino acid sequence of the peptide is not SEQ ID NO;
183, SEQ ID NO;
184, SEQ ID NO;
185, SEQ ID NO;
186, SEQ ID NO;
369, or SEQ ID NO;
378.- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 97, 98)
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33. A method of treating age-related hearing loss, the method comprising administering to a subject in need or want of relief thereof a therapeutically-effective amount of a peptide that is:
- a peptide of Formula (I) or Formula (II),
(capN)(capN)N-tranN-pepN-(X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12)x-pepC-tranC-C(O)-capC
Formula (I),
(capN)(capN)N-tranN-pepN-(X12-X11-X10-X9-X8-X7-X6-X5-X4-X3-X2-X1)x-pepC-tranC-C(O)-capC
Formula (II), whereineach capN is independently H, alkyl, aryl, aralkyl, an acyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, or an aminocarbonyl group, or both capN groups together with N form a heterocycle; tranN and tranC are each independently a transducing sequence or absent; pepN and pepC are each independently an amino acid sequence or absent; X1 is A, K, an acidic amino acid residue, or is absent; X2 is A, I, L, or V; X3 is A, D, I, L, P, or V; X4 is A, E, I, Y, or a basic amino acid residue; X5 is A, I, L, or V; X6 is A, G, S, T, or Y; X7 is A, E, I, L, or V; X8 is A, P, S, T, or an aromatic amino acid residue; X9 is A, K, or an acidic amino acid residue; X10 is A, C, M, S, α
-aminobutyric acid, or norvaline;X11 is A, I, L, V, or is absent; X12 is G or is absent; x is 1, 2, or 3; capC is OH, alkoxy, aryloxy, arylalkoxy, amino, alkylamino, dialkylamino, or a heterocycle; and each amino acid residue side chain is independently uncapped or capped with a capping group, or a stereoisomer or pharmaceutically-acceptable salt of any of the foregoing peptides, wherein the amino acid sequence of the peptide is not SEQ ID NO;
183, SEQ ID NO;
184, SEQ ID NO;
185, SEQ ID NO;
186, SEQ ID NO;
369, or SEQ ID NO;
378.- View Dependent Claims (34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 99, 100)
- a peptide of Formula (I) or Formula (II),
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65. A method of improving hearing, the method comprising administering to a subject in need or want thereof a therapeutically-effective amount of a peptide that is:
- a peptide of Formula (I) or Formula (II),
(capN)(capN)N-tranN-pepN-(X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12)x-pepC-tranC-C(O)-capC
Formula (I),
(capN)(capN)N-tranN-pepN-(X12-X11-X10-X9-X8-X7-X6-X5-X4-X3-X2-X1)x-pepC-tranC-C(O)-capC
Formula (II), whereineach capN is independently H, alkyl, aryl, aralkyl, an acyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, or an aminocarbonyl group, or both capN groups together with N form a heterocycle; tranN and tranC are each independently a transducing sequence or absent; pepN and pepC are each independently an amino acid sequence or absent; X1 is A, K, an acidic amino acid residue, or is absent; X2 is A, I, L, or V; X3 is A, D, I, L, P, or V; X4 is A, E, I, Y, or a basic amino acid residue; X5 is A, I, L, or V; X6 is A, G, S, T, or Y; X7 is A, E, I, L, or V; X8 is A, P, S, T, or an aromatic amino acid residue; X9 is A, K, or an acidic amino acid residue; X10 is A, C, M, S, α
-aminobutyric acid, or norvaline;X11 is A, I, L, V, or is absent; X12 is G or is absent; x is 1, 2, or 3; capC is OH, alkoxy, aryloxy, arylalkoxy, amino, alkylamino, dialkylamino, or a heterocycle; and each amino acid residue side chain is independently uncapped or capped with a capping group, or a stereoisomer or pharmaceutically-acceptable salt of any of the foregoing peptides, wherein the amino acid sequence of the peptide is not SEQ ID NO;
183, SEQ ID NO;
184, SEQ ID NO;
185, SEQ ID NO;
186, SEQ ID NO;
369, or SEQ ID NO;
378.- View Dependent Claims (66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 101, 102)
- a peptide of Formula (I) or Formula (II),
Specification