IMMUNOREGULATORY PEPTIDES AND METHODS OF USE

• US 20100317564A1
• Filed: 06/04/2010
• Published: 12/16/2010
• Est. Priority Date: 06/05/2009
• Status: Active Grant

• Current Assignee: 13therapeutics, Inc.
• Original Assignee: 13therapeutics, Inc.
• Inventors: Hefeneider, Steven H., McCoy, Sharon L.
• Granted Patent: US 8,450,285 B2
• Time in Patent Office: Days
• US Class Current: 514/1.4
• 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 composition comprising a peptide comprising:

a) a sequence of any one of SEQ ID NOS;

187-368;

or

b) a derivative of P13 comprising at least one D-amino acid residue.

2. The pharmaceutical composition of claim 1, wherein the peptide further comprises a transducing sequence at the C-terminus.

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

4. The pharmaceutical composition of claim 3, wherein the transducing sequence comprises nine consecutive arginine residues.

5. The pharmaceutical composition of claim 3, wherein the transducing sequence consists of nine consecutive arginine residues.

6. The pharmaceutical composition of claim 3, wherein the peptide comprises a derivative of P13 comprising at least one D-amino acid residue.

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

8. The pharmaceutical composition of claim 6, wherein all the amino acid residues that are not part of the transducing sequence are D-amino acid residues.

9. The pharmaceutical composition of claim 6, wherein at least one amino acid residue of the transducing sequence is a D-amino acid residue.

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

11. The pharmaceutical composition of claim 2, wherein the peptide is any one of SEQ ID NOS:

42-44, 68-77, 79-81, 83, 102-106, 133, 141, 151, 166, 167, 181, and 182.

12. The pharmaceutical composition of claim 1, wherein the peptide is any one of SEQ ID NOS:

228-230, 254-263, 265-267, 269, 288-292, 319, 327, 337, 352, 353, 367, and 368.

13. The pharmaceutical composition of claim 1 or 2, further comprising a pharmaceutically acceptable excipient.

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

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

16. A pharmaceutical composition comprising a peptide comprising a sequence of any one of

SEQ ID NOS:

1-186.

17. A peptide comprising the sequence of any one of SEQ ID NOS:

1-368.

18. The peptide of claim 17, comprising the sequence of any one of SEQ ID NOS:

42-44, 68-77, 79-81, 83, 102-106, 133, 141, 151, 166, 167, 181, 182, 228-230, 254-263, 265-267, 269, 288-292, 319, 327, 337, 352, 353, 367, and 368.

19. A derivative of a peptide comprising the sequence of any one of SEQ ID NOS:

1-369, wherein the derivative comprises at least one D-amino acid residue.

20. A method of regulating cellular activity, the method comprising administering to an organism in need or want thereof an effective amount of a pharmaceutical composition comprising a peptide comprising:

a) a sequence of any one of SEQ ID NOS;

187-368;

or

b) a derivative of P13 comprising at least one D-amino acid residue,

wherein the peptide optionally further comprises a transducing sequence at the C-terminus.

21. The method of claim 20, wherein the cellular activity is mediated by a toll-like receptor.

22. The method of claim 21, wherein the cellular activity mediated by a toll-like receptor is TNF-α

secretion.

23. The method of claim 20, providing 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80% or 90% inhibition of TNF-α

secretion following stimulation by LPS and/or CpG-ODN.

24. The method of claim 20, wherein the administering results in an inhibition of cytokine secretion.

25. A method of treating inflammation in an animal, the method comprising administering to an animal in need or want thereof a pharmaceutical composition comprising a peptide comprising:

a) a sequence of any one of SEQ ID NOS;

187-368;

or

b) a derivative of P13 comprising at least one D-amino acid residue,

wherein the peptide optionally further comprises a transducing sequence at the C-terminus.

26. The method of claim 25, wherein the inflammation is caused by a virus, bacteria, fungi, antigen, self-antigen, or a combination thereof.

27. The method of claim 25, wherein the inflammation is ear inflammation.

28. The method of claim 25, wherein the inflammation is otitis media.

29. The method of claim 28, wherein the administration reduces or eliminates a symptom of otitis media.

30. The method of claim 29, wherein the symptom is pain, otorrhea, fever, irritability, anorexia, vomiting or diarrhea.

31. The method of claim 29, wherein the symptom is pain.

32. The method of claim 25, wherein the inflammation is inflammation of the skin, joints, muscular tissue, brain, or connective tissue.

33. The method of claim 25, wherein the inflammation is arthritis, dermatitis, Lupus erythematosus, meningitis, or psoriasis.

34. The method of claim 33, wherein the arthritis is osteoarthritis, rheumatoid arthritis, septic arthritis, gout, pseudo-gout, juvenile idiopathic arthritis, Still'"'"'s disease, or ankylosing spondylitis.

35. The method of claim 33, wherein the dermatitis is spongiotic dermatitis, childhood eczema, allergic contact dermatitis, seborrhoeic dermatitis, dyshidrotic dermatitis, urticaria, vesicular or bullous dermatitis, or papular urticaria.

36. The method of claim 33, wherein the psoriasis is plaque psoriasis, flexural psoriasis, guttate psoriasis, pustular psoriasis, nail psoriasis, psoriatic arthritis, or erythrodermic psoriasis.

37. The method of claim 25, wherein the pharmaceutical composition is administered via topical application.

38. The method of claim 37, wherein the topical application comprises application to the skin, hair, outer ear, tympanic membrane, buccal cavity, nasal cavity, or sublingual cavity.

39. The method of claim 38, wherein the topical application comprises application to the tympanic membrane.

40. The method of claim 38, wherein the application to the tympanic membrane comprises the application of drops to the tympanic membrane.

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

42. A method of treating sinusitis, the method comprising administering an aerosol composition to an organism in need or want thereof, the aerosol composition comprising a therapeutically-effective amount of a peptide comprising:

a) a sequence of any one of SEQ ID NOS;

187-369;

or

b) a derivative of P13 comprising at least one D-amino acid residue,

wherein the peptide optionally further comprises a transducing sequence at the C-terminus.

43. A method of improving hearing in an animal, the method comprising administering to an animal having middle and/or inner ear inflammation and reduced hearing a therapeutically-effective amount of a peptide comprising:

a) a sequence of any one of SEQ ID NOS;

187-369;

or

b) a derivative of P13 comprising at least one D-amino acid residue,

wherein the peptide optionally further comprises a transducing sequence at the C-terminus, wherein the peptide is administered topically, wherein the hearing improves to a level no better than ordinary levels, and/or the hearing improves faster than the hearing would improve without administration of the peptide.

44. A method of treating middle and/or inner ear inflammation, the method comprising administering to a tympanic membrane of an animal in need or want thereof a therapeutically-effective amount of a peptide comprising:

a) a sequence of any one of SEQ ID NOS;

187-369;

or

b) a derivative of P13 comprising at least one D-amino acid residue,

wherein the peptide optionally further comprises a transducing sequence at the C-terminus.