Immunoregulatory peptides and methods of use

• US 8,450,285 B2
• Filed: 06/04/2010
• Issued: 05/28/2013
• 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:
  US12/794,185
• Publication Number:
  US 20100317564A1
• Time in Patent Office: 1,089 Days
• Field of Search: None
• US Class Current: 514/21.6
• 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 SEQ ID NO:

319 conjugated to a transducing sequence at the 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 peptide composition of claim 1, wherein the peptide is SEQ ID NO:

133.

8. The pharmaceutical peptide composition of claim 1 or 2, wherein the pharmaceutical peptide composition is in the form of a drop.

9. The pharmaceutical peptide composition of claim 1 or 2, wherein the pharmaceutical peptide composition is in the form of an aerosol, vapor, spray, or mist.

10. A synthetic peptide of SEQ ID NO:

319 conjugated to a transducing sequence at the C-terminus, wherein at least one amino acid residue of the synthetic peptide is in the D-configuration.

11. A method of inhibiting cellular activity mediated by a toll-like receptor, the method comprising administering to an organism in need thereof an effective amount of a pharmaceutical peptide composition comprising SEQ ID NO:

319 conjugated to a transducing sequence at the C-terminus and a pharmaceutically-acceptable excipient, wherein the pharmaceutical composition is in a unit dosage form.

12. The method of claim 11, wherein the cellular activity mediated by a toll-like receptor is TNF-α

secretion.

13. The method of claim 11, wherein the inhibition of cellular activity mediated by the toll-like receptor results in an inhibition of cytokine secretion.

14. A method of treating inflammation in an animal, the method comprising administering to an animal in need thereof a therapeutically-effective amount of a pharmaceutical peptide composition comprising SEQ ID NO:

319 conjugated to a transducing sequence at the C-terminus and a pharmaceutically-acceptable excipient, wherein the pharmaceutical composition is in a unit dosage form.

15. The method of claim 14, wherein the inflammation is caused by a bacteria.

16. The method of claim 14, wherein the inflammation is ear inflammation.

17. The method of claim 14, wherein the inflammation is otitis media.

18. The method of claim 17, wherein treating the inflammation alleviates a symptom of otitis media.

19. The method of claim 18, wherein the symptom is pain.

20. The method of claim 14, wherein the inflammation is inflammation of the skin.

21. The method of claim 14, wherein the pharmaceutical peptide composition is administered via topical application.

22. The method of claim 21, wherein the topical application comprises application to the skin, hair, outer ear, tympanic membrane, buccal cavity, nasal cavity, or sublingual cavity.

23. The method of claim 22, wherein the topical application comprises application to the tympanic membrane.

24. The method of claim 22, wherein the application to the tympanic membrane comprises the application of drops to the tympanic membrane.

25. The method of claim 14, wherein the animal is a human.

26. A method of treating hearing impairment in an animal, the method comprising administering a therapeutically-effective amount of a peptide composition comprising SEQ ID NO:

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

27. A method of treating middle and/or inner ear inflammation, the method comprising administering a therapeutically-effective amount of a peptide composition comprising SEQ ID NO:

319 conjugated to a transducing sequence at the C-terminus to a tympanic membrane of an animal in need thereof.

28. A synthetic peptide SEQ ID NO:

319 conjugated to a transducing sequence at the C-terminus.

29. The synthetic peptide of claim 28, wherein the transducing sequence is a poly-arginine sequence.

30. The synthetic peptide of claim 28, wherein the transducing sequence comprises nine consecutive arginine residues (SEQ ID NO:

379).

31. The synthetic peptide of claim 28, wherein the transducing sequence consists of nine consecutive arginine residues (SEQ ID NO:

379).

32. The synthetic peptide of claim 28, wherein at least one amino acid residue of the transducing sequence is a D-amino acid residue.

33. The synthetic peptide of claim 28, wherein all the amino acid residues of the transducing sequence are D-amino acid residues.