Immunoregulatory peptides and methods of use

• US 9,974,853 B2
• Filed: 10/06/2015
• Issued: 05/22/2018
• Est. Priority Date: 06/05/2009
• Status: Active Grant

• Current Assignee: 13therapeutics, Inc.
• Original Assignee: 13therapeutics, Inc.
• Inventors: McCoy, Sharon L., Hefeneider, Steven H.
• Primary Examiner(s): GUDIBANDE, SATYANARAYAN R
• Application Number:
  US14/876,298
• Publication Number:
  US 20160250320A1
• Time in Patent Office: 959 Days
• Field of Search: None
• 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. A pharmaceutical peptide composition comprising:

a peptide-transducing sequence conjugate, wherein the peptide comprises SEQ ID NO.;

327, SEQ ID NO.;

368, SEQ ID NO.;

352, SEQ ID NO.;

367, or SEQ ID NO.;

353; and

wherein the peptide is conjugated to a transducing sequence at the peptide C-terminus; and

a pharmaceutically-acceptable excipient, wherein the pharmaceutical composition is in a unit dosage form.

2. The pharmaceutical peptide composition of claim 1, wherein the transducing sequence is a poly-arginine sequence.

3. The pharmaceutical peptide composition of claim 1, wherein the transducing sequence comprises nine consecutive arginine residues (SEQ ID NO:

379).

4. The pharmaceutical peptide composition of claim 1, wherein the transducing sequence consists of nine consecutive arginine residues (SEQ ID NO:

379).

5. The pharmaceutical peptide composition of claim 1, wherein at least one amino acid residue of the transducing sequence is a D-amino acid residue.

6. The pharmaceutical peptide composition of claim 1, wherein all the amino acid residues of the transducing sequence are D-amino acid residues.

7. The pharmaceutical peptide composition of claim 1, wherein the peptide is SEQ ID NO.:

327.

8. The pharmaceutical peptide composition of claim 1, wherein the peptide is SEQ ID NO.:

368.

9. The pharmaceutical peptide composition of claim 1, wherein the peptide is SEQ ID NO.:

352.

10. The pharmaceutical peptide composition of claim 1, wherein the peptide is SEQ ID NO.:

367.

11. The pharmaceutical peptide composition of claim 1, wherein the peptide is SEQ ID NO.:

353.

12. The pharmaceutical peptide composition of claim 1, wherein the peptide-transducing sequence conjugate is SEQ ID NO.:

141.

13. The pharmaceutical peptide composition of claim 1, wherein the peptide-transducing sequence conjugate is SEQ ID NO.:

182.

14. The pharmaceutical peptide composition of claim 1, wherein the peptide-transducing sequence conjugate is SEQ ID NO.:

166.

15. The pharmaceutical peptide composition of claim 1, wherein the peptide-transducing sequence conjugate is SEQ ID NO.:

181.

16. The pharmaceutical peptide composition of claim 1, wherein the peptide-transducing sequence conjugate is SEQ ID NO.:

167.

17. The pharmaceutical peptide composition of claim 1, wherein the pharmaceutical peptide composition is in the form of a drop.

18. A method of treating inflammation in an animal in need thereof, the method comprising:

administering to the animal in need thereof a therapeutically-effective amount of a peptide-transducing sequence conjugate, wherein the peptide comprises SEQ ID NO.;

327, SEQ ID NO.;

368, SEQ ID NO.;

352, SEQ ID NO.;

367, or SEQ ID NO.;

353; and

wherein the peptide is conjugated to a transducing sequence at the peptide C-terminus, wherein the pharmaceutical composition is in a unit dosage form.

19. A method of treating hearing impairment, the method comprising:

administering a therapeutically-effective amount of a peptide-transducing sequence conjugate, wherein the peptide comprises SEQ ID NO.;

327, SEQ ID NO.;

368, SEQ ID NO.;

352, SEQ ID NO.;

367, or SEQ ID NO.;

353; and

wherein the peptide is conjugated to a transducing sequence at the peptide C-terminus, to an animal having middle and/or inner ear inflammation and reduced hearing.