Small Cationic Antimicrobial Peptides

• US 20110236429A1
• Filed: 08/21/2007
• Published: 09/29/2011
• Est. Priority Date: 08/21/2006
• Status: Active Grant

• Current Assignee: University of British Columbia
• Original Assignee: University of British Columbia
• Inventors: Hilpert, Kai, Fjell, Christopher, Hancock, Robert E. W., Cherkasov, Artem
• Granted Patent: US 8,343,475 B2
• Time in Patent Office: Days
• US Class Current: 424/278.1
• CPC Class Codes: A01N 37/46 N-acyl derivatives
• 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 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/0005 Vertebrate antigens from snakes A61K39/38
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 14/4723 Cationic antimicrobial peptides, e.g. defensins
• 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: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates generally to peptides and more specifically to antimicrobial and immunomodulatory host defense peptides.

Claims

1-146. -146. (canceled)

147. An isolated immunomodulatory peptide comprising an amino acid sequence of SEQ ID NO:

2 or a related peptide comprising an amino acid sequence of SEQ ID NO;

1213, 1214, 1222, 1224, 1230, 1232, 12, or 1238, or an amino acid sequence having 90% identity thereto.

148. An isolated polynucleotide that encodes a peptide of claim 147.

149. A pharmaceutical composition comprising an isolated immunomodulatory peptide of claim 147.

150. A method for suppressing a pro-inflammatory response comprising contacting a cell that expresses at least one pro-inflammatory cytokine, mediator or protein in response to a pro-inflammatory stimulus with an effective amount of a composition comprising a peptide of claim 147, wherein contacting the cell with the composition inhibits the expression of the at least one pro-inflammatory cytokine, mediator, or protein.

151. The method of claim 150, wherein the composition inhibits the inflammatory or septic response.

152. The method of claim 150, wherein the composition inhibits the expression of a pro-inflammatory gene or molecule.

153. The method of claim 150, wherein the composition inhibits the expression of TNF-α

.

154. The method of claim 150, wherein the inflammatory response is induced by a microbe or a microbial ligand acting on a Toll-like receptor.

155. The method of claim 154, wherein the microbial ligand is a bacterial endotoxin or lipopolysaccharide.

156. A method for enhancing innate immunity comprising contacting a cell that expresses at least one polypeptide involved in innate immunity with an effective amount of a composition comprising a peptide of claim 147, wherein contacting the cell with the composition modulates the expression of the at least one polypeptide involved in innate immunity.

157. The method of claim 156, wherein the expression of at least one polypeptide involved in innate immunity is inhibited.

158. The method of claim 156, wherein the polypeptide involved in innate immunity is a chemokine or cytokine.

159. The method of claim 156, wherein the polypeptide involved in innate immunity is encoded by the gene MCP-1, MCP-3, IL-8, or Gro-α

.

160. A method for inhibiting an inflammatory or septic response in a subject comprising administering to the subject a composition comprising a pharmaceutically acceptable carrier and an immunomodulatory peptide of claim 147 in an amount effective to inhibit an inflammatory or septic response in the subject.

161. The method of claim 160, further comprising administering at least one antibiotic or lysozyme.

162. The method of claim 161, wherein the antibiotic is selected from the group consisting of amikacin, gentamicin, kanamycin, netilmicin, tobramycin, streptomycin, azithromycin, clarithromycin, erythromycin, erythromycin estolate/ethyl-succinate/gluceptate/lactobionate/stearate, penicillin G, penicillin V, methicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, ampicillin, amoxicillin, ticarcillin, carbenicillin, mezlocillin, azlocillin, piperacillin, cephalothin, cefazolin, cefaclor, cefamandole, cefoxitin, cefuroxime, cefonicid, cefmetazole, cefotetan, cefprozil, loracarbef, cefetamet, cefoperazone, cefotaxime, ceftizoxime, ceftriaxone, ceftazidime, cefepime, cefixime, cefpodoxime, cefsulodin, imipenem, aztreonam, fleroxacin, nalidixic acid, norfloxacin, ciprofloxacin, ofloxacin, enoxacin, lomefloxacin, cinoxacin, doxycycline, minocycline, tetracycline, vancomycin, chloramphenicol, clindamycin, trimethoprim, sulfamethoxazole, nitrofurantoin, rifampin and mupirocin and teicoplanin.

163. The method of claim 160, wherein the peptide is bound to a solid support.

164. The method of claim 163, wherein the solid support is a medical device.