IP Library › Granted Patent US 8,518,871
Granted Patent B2
US 8,518,871 · App. 13/253,796 · Granted Aug 27, 2013

Skin permeating and cell entering (SPACE) peptides and methods of use thereof

Inventors: Tracy Hsu (Newhall, CA); Samir M. Mitragotri (Santa Barbara, CA)
Assignee: The Regents of the University of California
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Quick Facts
Patent No.
US 8,518,871
App. No.
13/253,796
Granted
Aug 27, 2013
Kind
B2
Abstract

The present disclosure provides peptides and peptide compositions, which facilitate the delivery of an active agent or an active agent carrier wherein the compositions are capable of penetrating the stratum corneum (SC) and/or the cellular membranes of viable cells.

Claims (42)

1. A composition comprising a peptide comprising the amino acid sequence selected from the group consisting of CHSALTKHC (SEQ ID NO:8), CKTGSHNQC (SEQ ID NO:9), CMGPSSMLC (SEQ ID NO: 10), CTDPNQLQC (SEQ ID NO: 11), CSTHFIDTC (SEQ ID NO: 12), ACTGSTQHQCG (SEQ ID NO: 13), ACHSALTKHCG (SEQ ID NO: 14), ACKTGSHNQCG (SEQ ID NO: 15), ACMGPSSMLCG (SEQ ID NO: 16), ACTDPNQLQCG (SEQ ID NO: 17), and ACSTHFIDTCG (SEQ ID NO: 18), wherein the peptide is associated with or conjugated to an active agent or an active agent carrier comprising the active agent, and wherein the composition is capable of penetrating a stratum corneum (SC) layer when contacted therewith or penetrating a cell when contacted therewith.

2. The composition of claim 1 , wherein the composition is capable of penetrating the SC layer and penetrating the cell.

3. The composition of claim 1 , wherein the peptide is a cyclic peptide comprising a Cys-Cys disulfide bond.

4. The composition of claim 1 , wherein the composition is capable of penetrating the cellular membrane of a cell selected from the group consisting of a viable non-human animal cell, a viable human cell, a viable epidermal cell, a viable dermal cell, and a viable immunological cell.

5. The composition of claim 1 , wherein the active agent comprises a protein, a nucleic acid, a pharmaceutical compound, a detectable agent, a nanoparticle, or a low molecular weight compound.

6. The composition of claim 5 , wherein the active agent comprises a protein and the protein comprises an antibody or a fragment thereof comprising at least one paratope.

7. The composition of claim 5 , wherein the active agent comprises a nucleic acid and the nucleic acid is DNA.

8. The composition of claim 5 , wherein the active agent comprises a nucleic acid and the nucleic acid is RNA.

9. The composition of claim 8 , wherein the RNA is interfering RNA.

10. The composition of claim 9 , wherein the interfering RNA is an shRNA, an miRNA, or an siRNA.

11. The composition of claim 10 , wherein the interfering RNA is an siRNA and the siRNA is selected from the group consisting of an IL-10 siRNA, a CD86 siRNA, a KRT6a siRNA, a TNFR1 siRNA, and a TACE siRNA.

12. The composition of claim 10 , wherein the interfering RNA is an siRNA and the siRNA is a mutation-specific siRNA.

13. The composition of claim 5 , wherein the active agent comprises a detectable agent and the detectable agent comprises a fluorescent label or a radioactive label.

14. The composition of claim 1 , wherein the active agent is an inhibitor of IL-10 biological activity.

15. The composition of claim 14 , wherein the active agent is selected from an IL-10 siRNA and antibodies or fragments thereof that bind IL-10.

16. The composition of claim 1 , wherein the peptide is conjugated to the active agent carrier comprising the active agent and the active agent carrier is selected from the group consisting of a liposome, a nanoparticle, and a polymeric micelle.

17. The composition of claim 1 , wherein the peptide is associated with the active agent or the active agent carrier comprising the active agent, via hydrophobic, electrostatic or van der Walls interactions.

18. An isolated peptide comprising the amino acid sequence selected from one of the following sequences: CHSALTKHC (SEQ ID NO:8), CKTGSHNQC (SEQ ID NO:9), CMGPSSMLC (SEQ ID NO: 10), CTDPNQLQC (SEQ ID NO: 11), CSTHFIDTC (SEQ ID NO: 12), ACTGSTQHQCG (SEQ ID NO: 13), ACHSALTKHCG (SEQ ID NO: 14), ACKTGSHNQCG (SEQ ID NO: 15), ACMGPSSMLCG (SEQ ID NO: 16), ACTDPNQLQCG (SEQ ID NO: 17), and ACSTHFIDTCG (SEQ ID NO: 18), wherein the peptide is associated with or conjugated to an active agent or an active agent carrier comprising the active agent, and wherein the composition is capable of penetrating a stratum corneum (SC) layer when contacted therewith or penetrating a cell when contacted therewith.

19. The isolated peptide of claim 18 , wherein the peptide comprises repeat units of one or more of CHSALTKHC (SEQ ID NO:8), CKTGSHNQC (SEQ ID NO:9), CMGPSSMLC (SEQ ID NO:10), CTDPNQLQC (SEQ ID NO:11), CSTHFIDTC (SEQ ID NO:12), ACTGSTQHQCG (SEQ ID NO:13), ACHSALTKHCG (SEQ ID NO:14), ACKTGSHNQCG (SEQ ID NO:15), ACMGPSSMLCG (SEQ ID NO:16), ACTDPNQLQCG (SEQ ID NO:17), and ACSTHFIDTCG (SEQ ID NO:18).

20. The isolated peptide of claim 19 , wherein the unit is repeated 2 to 50 times.

21. The isolated peptide of claim 19 , wherein each unit is separated by an intervening peptide sequence.

22. The isolated peptide of claim 18 , wherein the peptide is a cyclic peptide comprising a Cys-Cys disulfide bond.

23. A composition comprising a peptide consisting of the amino acid sequence selected from one of the following sequences: CHSALTKHC (SEQ ID NO:8), CKTGSHNQC (SEQ ID NO:9), CMGPSSMLC (SEQ ID NO: 10), CTDPNQLQC (SEQ ID NO: 11), CSTHFIDTC (SEQ ID NO: 12), ACTGSTQHQCG (SEQ ID NO: 13), ACHSALTKHCG (SEQ ID NO: 14), ACKTGSHNQCG (SEQ ID NO: 15), ACMGPSSMLCG (SEQ ID NO: 16), ACTDPNQLQCG (SEQ ID NO: 17), and ACSTHFIDTCG (SEQ ID NO: 18), wherein the peptide is associated with or conjugated to an active agent or an active agent carrier comprising the active agent, and wherein the composition is capable of penetrating a stratum corneum (SC) layer when contacted therewith or penetrating a cell when contacted therewith.

24. The composition of claim 1 , wherein the peptide comprises SEQ ID NO. 13.

25. The composition of claim 1 , wherein the peptide comprises SEQ ID NO. 14.

26. The composition of claim 1 , wherein the peptide comprises SEQ ID NO. 15.

27. The composition of claim 1 , wherein the peptide comprises SEQ ID NO. 16.

28. The composition of claim 1 , wherein the peptide comprises SEQ ID NO. 17.

29. The composition of claim 3 , wherein the peptide comprises SEQ ID NO. 13.

30. The composition of claim 3 , wherein the peptide comprises SEQ ID NO. 14.

31. The composition of claim 3 , wherein the peptide comprises SEQ ID NO. 15.

32. The composition of claim 3 , wherein the peptide comprises SEQ ID NO. 16.

33. The composition of claim 3 , wherein the peptide comprises SEQ ID NO. 17.

34. The isolated peptide of claim 18 , wherein the peptide comprises SEQ ID NO. 13.

35. The isolated peptide of claim 18 , wherein the peptide comprises SEQ ID NO. 14.

36. The isolated peptide of claim 18 , wherein the peptide comprises SEQ ID NO. 15.

37. The isolated peptide of claim 18 , wherein the peptide comprises SEQ ID NO. 16.

38. The isolated peptide of claim 18 , wherein the peptide comprises SEQ ID NO. 17.

39. The composition of claim 23 , wherein the peptide is a cyclic peptide comprising a Cys-Cys disulfide bond.

40. The composition of claim 1 , wherein the peptide is from 9 to 11 amino acids in length.

41. The composition of claim 1 , wherein the peptide is from about 12-15 amino acids in length.

42. The composition of claim 1 , wherein the peptide is from about 16-19 amino acids in length.

Assignments (2)
CONFIRMATORY LICENSE Recorded Feb 9, 2012
From: UNIVERSITY OF CALIFORNIA SANTA BARBARA
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 027676/0502 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 27, 2012
From: HSU, TRACY; MITRAGOTRI, SAMIR M.
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 027608/0247 →
Continuity (4)
Provisional Application 61411884 · Nov 9, 2010
Provisional Application 61527574 · Aug 25, 2011
Provisional Application 61528036 · Aug 26, 2011
Related Publication 20120128756A1 · May 24, 2012