IMMUNOREGULATORY PEPTIDES AND METHODS OF USE

• US 20130203683A1
• Filed: 01/29/2013
• Published: 08/08/2013
• Est. Priority Date: 06/05/2009
• Status: Active Grant

• Current Assignee: 13therapeutics, Inc.
• Original Assignee: 13 Therapeutics Incorporated
• Inventors: McCoy, Sharon L., Hefeneider, Steven H.
• Granted Patent: US 9,187,530 B2
• Time in Patent Office: Days
• US Class Current: 514/21.3
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/285 Vaccinia virus or variola virus
• CPC Class Codes: A61P 1/10 Laxatives
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 14/07 Vaccinia virus; Variola virus
• CPC Class Codes: C07K 14/47 : from mammals
• CPC Class Codes: C07K 2319/10 : containing a tag for extracellular membrane crossing, e.g. TAT or VP22
• CPC Class Codes: C07K 7/06 : having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 : having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: C12N 2710/24122 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

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 receptors. Experiments are described illustrating the efficacy of the compounds in treating otitis media

Claims

1-44. -44. (canceled)

45. A method of transporting a compound across a tympanic membrane in an animal in need or want thereof, the method comprising topically administering the compound to the tympanic membrane, whereupon the compound crosses the tympanic membrane, wherein the compound comprises a transducing sequence.

46. The method of claim 45, wherein the administering the compound to the tympanic membrane comprises administering the compound to an external tympanic membrane.

47. The method of claim 45, wherein the compound is administered in a unit dosage form comprising a pharmaceutically-acceptable excipient.

48. The method of claim 47, wherein the unit dosage form is an ointment, cream, liquid, gel, or salve.

49. The method of claim 47, wherein the unit dosage form is a drop.

50. The method of claim 47, wherein the unit dosage form is in the form of an aerosol, vapor, spray, or mist.

51. The method of claim 45, further comprising wherein the compound is taken up into an immune system cell after crossing the tympanic membrane.

52. The method of claim 45, wherein an amount of the compound that is therapeutically-effective for treatment of an inflammation crosses the tympanic membrane within 10 minutes of administration.

53. The method of claim 52, wherein the amount is therapeutically-effective to treat hearing impairment.

54. The method of claim 53, wherein the inflammation is associated with hearing impairment.

55. The method of claim 52, wherein the inflammation is middle ear inflammation.

56. The method of claim 52, wherein the inflammation is inner ear inflammation.

57. The method of claim 52, wherein the inflammation is otitis media.

58. The method of claim 52, wherein the therapeutically-effective amount is in a range of about 100 ng per kg to about 10 mg per kg of the animal.

59. The method of claim 45, wherein the transducing sequence is a polyarginine sequence.

60. The method of claim 45, wherein the transducing sequence comprises nine consecutive arginine residues.

61. The method of claim 45, wherein the transducing sequence consists of nine consecutive arginine residues.

62. The method of claim 45, wherein the compound is a peptide.

63. The method of claim 62, wherein the transducing sequence is at the C-terminus of the peptide.

64. The method of claim 62, wherein the peptide has at least one D-amino acid residue.

65. The method of claim 62, wherein the peptide is any one of SEQ ID NOs:

187-369 conjugated to the transducing sequence at the C-terminus of the peptide.

66. The method of claim 62, wherein the peptide is any one of SEQ ID NOs:

317-369 conjugated to the transducing sequence at the C-terminus of the peptide.

67. The method of claim 62, wherein the peptide is SEQ ID NO:

319 conjugated to the transducing sequence at the C-terminus of the peptide.

68. The method of claim 62, wherein the peptide is SEQ ID NO:

327 conjugated to the transducing sequence at the C-terminus of the peptide.

69. The method of claim 62, wherein the peptide is SEQ ID NO:

337 conjugated to the transducing sequence at the C-terminus of the peptide.

70. The method of claim 62, wherein the peptide is SEQ ID NO:

352 conjugated to the transducing sequence at the C-terminus of the peptide.

71. The method of claim 62, wherein the peptide is SEQ ID NO:

353 conjugated to the transducing sequence at the C-terminus of the peptide.

72. The method of claim 62, wherein the peptide is SEQ ID NO:

367 conjugated to the transducing sequence at the C-terminus of the peptide.

73. The method of claim 62, wherein the peptide is SEQ ID NO:

368 conjugated to the transducing sequence at the C-terminus of the peptide.

74. The method of claim 62, wherein the peptide is SEQ ID NO:

369 conjugated to the transducing sequence at the C-terminus of the peptide.

75. The method of claim 62, wherein the peptide is any one of SEQ ID NOs:

1-186 and 378.

76. The method of claim 62, wherein the peptide is any one of SEQ ID NOs:

131-186 and 378.

77. The method of claim 62, wherein the peptide is SEQ ID NO:

133.

78. The method of claim 62, wherein the peptide is SEQ ID NO:

378.

79. The method of claim 62, wherein the peptide is SEQ ID NO:

141.

80. The method of claim 62, wherein the peptide is SEQ ID NO:

151.

81. The method of claim 62, wherein the peptide is SEQ ID NO:

166.

82. The method of claim 62, wherein the peptide is SEQ ID NO:

167.

83. The method of claim 62, wherein the peptide is SEQ ID NO:

181.

84. The method of claim 62, wherein the peptide is SEQ ID NO:

182.

85. The method of claim 45, wherein the animal is human.

86. A pharmaceutical composition comprising:

(a) a compound, wherein the compound comprises a transducing sequence; and

(b) a pharmaceutically-acceptable excipient,

wherein the pharmaceutical composition is provided in a unit dosage form suitable for application directly to a tympanic membrane in an animal, and wherein the pharmaceutical composition is formulated to allow passage of the compound through the tympanic membrane upon direct application of the unit dosage form to the tympanic membrane.

87. The pharmaceutical composition of claim 86, wherein the unit dosage form is in the form of a drop.

88. The pharmaceutical composition of claim 86, wherein the unit dosage form is an ointment, cream, liquid, gel, or salve.

89. The pharmaceutical composition of claim 86, wherein the unit dosage form is in the form of an aerosol, vapor, spray, or mist.

90. The pharmaceutical composition of claim 86, wherein the transducing sequence is a polyarginine sequence.

91. The pharmaceutical composition of claim 86, wherein the transducing sequence comprises nine consecutive arginine residues.

92. The pharmaceutical composition of claim 86, wherein the transducing sequence consists of nine consecutive arginine residues.

93. The pharmaceutical composition of claim 86, wherein the compound is a peptide.

94. The pharmaceutical composition of claim 93, wherein the peptide is any one of SEQ ID NOs:

187-369 conjugated to the transducing sequence at the C-terminus of the peptide.

95. The pharmaceutical composition of claim 93, wherein the peptide is any one of SEQ ID NOs:

317-369 conjugated to the transducing sequence at the C-terminus of the peptide.

96. The pharmaceutical composition of claim 93, wherein the peptide is SEQ ID NO:

319 conjugated to the transducing sequence at the C-terminus of the peptide.

97. The pharmaceutical composition of claim 93, wherein the peptide is SEQ ID NO:

327 conjugated to the transducing sequence at the C-terminus of the peptide.

98. The pharmaceutical composition of claim 93, wherein the peptide is SEQ ID NO:

337 conjugated to the transducing sequence at the C-terminus of the peptide.

99. The pharmaceutical composition of claim 93, wherein the peptide is SEQ ID NO:

352 conjugated to the transducing sequence at the C-terminus of the peptide.

100. The pharmaceutical composition of claim 93, wherein the peptide is SEQ ID NO:

353 conjugated to the transducing sequence at the C-terminus of the peptide.

101. The pharmaceutical composition of claim 93, wherein the peptide is SEQ ID NO:

367 conjugated to the transducing sequence at the C-terminus of the peptide.

102. The pharmaceutical composition of claim 93, wherein the peptide is SEQ ID NO:

368 conjugated to the transducing sequence at the C-terminus of the peptide.

103. The pharmaceutical composition of claim 93, wherein the peptide is SEQ ID NO:

369 conjugated to the transducing sequence at the C-terminus of the peptide.

104. The pharmaceutical composition of claim 93, wherein the peptide is any one of SEQ ID NOs:

1-186 and 378.

105. The pharmaceutical composition of claim 93, wherein the peptide is any one of SEQ ID NOs:

131-186 and 378.

106. The pharmaceutical composition of claim 93, wherein the peptide is SEQ ID NO:

133.

107. The pharmaceutical composition of claim 93, wherein the peptide is SEQ ID NO:

378.

108. The pharmaceutical composition of claim 93, wherein the peptide is SEQ ID NO:

141.

109. The pharmaceutical composition of claim 93, wherein the peptide is SEQ ID NO:

151.

110. The pharmaceutical composition of claim 93, wherein the peptide is SEQ ID NO:

166.

111. The pharmaceutical composition of claim 93, wherein the peptide is SEQ ID NO:

167.

112. The pharmaceutical composition of claim 93, wherein the peptide is SEQ ID NO:

181.

113. The pharmaceutical composition of claim 93, wherein the peptide is SEQ ID NO:

182.