IP Library Granted Patent US 9,566,347
Granted Patent B2
US 9,566,347 · App. 13/976,319 · Granted Feb 14, 2017

Peptides and methods using same

Inventors: Dennis E. Discher (Philadelphia, PA); Pia L. Rodriguez Nunez (Philadelphia, PA); Diego A. Pantano (Philadelphia, PA)
Assignee: The Trustees of the University of Pennsylvania
A61K47/48246A61K38/177A61K47/48853C07K7/06C07K7/08C07K14/001C07K14/70596A61K38/00
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Quick Facts
Patent No.
US 9,566,347
App. No.
13/976,319
Granted
Feb 14, 2017
Kind
B2
Abstract

The present invention includes a method of modulating the phagocytic activity of at least one phagocyte in a subject. The present invention also includes a method of providing a composition resistant to phagocytosis to a subject. The present invention further includes a method of treating, ameliorating or preventing an inflammatory disease in a subject.

Claims (67)

1. A peptide of SEQ ID NO:2, or a salt thereof, wherein:

(i) Xaa 1 is Thr; and Xaa 12 is selected from the group consisting of Thr and null, or

(ii) Xaa 1 is selected from the group consisting of Cys, Thr and null; and Xaa 12 is Cys.

2. The peptide of claim 1 , or a salt thereof, wherein Xaa 1 is Thr and Xaa 12 is Cys.

3. The peptide of claim 1 , or a salt thereof, wherein Xaa 1 is null and Xaa 12 is Cys.

4. The peptide of claim 1 , which consists of SEQ ID NO:4, or a salt thereof.

5. The peptide of claim 1 , or a salt thereof, wherein Xaa 1 is Thr and Xaa 12 is Thr.

6. The peptide of claim 1 , or a salt thereof, wherein Xaa 1 is Thr and Xaa 12 is null.

7. A composition comprising:

compound (II) or a salt thereof:

compound (III) or a salt thereof:

compound (IV) or a salt thereof:

or

compound (V) or a salt thereof:

wherein:

P 1 comprises a peptide having at least 85% homology with the peptide of SEQ ID NO:2, and

P 1 is covalently bound through its N-amino terminus via an amide bond to the carbonyl group (1′).

8. The composition of claim 7 , wherein said P 1 comprises a peptide having at least 85% homology with the peptide of SEQ ID NO:3.

9. The composition of claim 7 , wherein said P 1 comprises a peptide having at least 85% homology with the peptide of SEQ ID NO:4.

10. The composition of claim 7 , wherein said P 1 comprises a peptide having at least 85% homology with the peptide of SEQ ID NO:1.

11. A composition comprising a chemical agent comprising a compound selected from the group consisting of compounds (II)-(V), wherein said chemical agent is attached to the surface of a solid particle.

12. The composition of claim 11 , wherein said solid particle is selected from the group consisting of a nanoparticle, vesicle, dendrimer, engineered cell, tissue fragment, implant, and combinations thereof.

13. The composition of claim 11 , further comprising an additional agent selected from the group consisting of a therapeutic agent, imaging agent, radioactive agent, salt, protein, nucleic acid, gas, and combinations thereof, wherein said additional agent is attached to or contained within said solid particle.

14. The composition of claim 11 , wherein said chemical agent moiety is attached to said surface of said solid particle by a covalent or non-covalent bond.

15. A method of inhibiting phagocytic activity of at least one phagocyte in a subject, said method comprising administering to said subject a pharmaceutical composition comprising a pharmaceutically effective amount of a peptide-containing moiety or a salt thereof,

wherein said peptide-containing moiety comprises a compound selected from the group consisting of:

a peptide of SEQ ID NO:2, wherein: (i) Xaa 1 is Thr; and Xaa 12 is selected from the group consisting of Thr and null, or (ii) Xaa 1 is selected from the group consisting of Cys, Thr and null; and Xaa 12 is Cys;

compound (II):

compound (III):

compound (IV):

or

compound (V):

wherein in (II)-(V) P 1 comprises a peptide having at least 85% homology with the peptide of SEQ ID NO:2, and is covalently bound through its N-amino terminus via an amide bond to the carbonyl group (1′);

whereby administering said composition to said subject inhibits phagocytic activity of said at least one phagocyte in said subject.

16. The method of claim 15 , wherein said composition further comprises a solid particle, wherein said peptide-containing moiety is attached to said surface of said solid particle.

17. The method of claim 16 , wherein said solid particle is selected from the group consisting of a nanoparticle, vesicle, dendrimer, engineered cell, tissue fragment, implant, and combinations thereof.

18. The method of claim 16 , wherein said composition further comprises an agent selected from the group consisting of a therapeutic agent, imaging agent, radioactive agent, salt, protein, nucleic acid, gas, and combinations thereof, wherein said agent is attached to or contained within said solid particle.

19. The method of claim 15 , wherein said composition further comprises a conjugated compound covalently linked to said peptide-containing moiety.

20. The method of claim 19 , wherein said conjugated compound is selected from the group consisting of a peptide, protein, nucleic acid, lipid, biologically active molecule, and combinations thereof.

21. A method of inhibiting phagocytosis in a subject, said method comprising administering to or introducing into said subject a pharmaceutical composition comprising a peptide-containing moiety or a salt thereof, wherein said peptide-containing moiety comprises a compound selected from the group consisting of:

a peptide of SEQ ID NO:2, wherein: (i) Xaa 1 is Thr; and Xaa 12 is selected from the group consisting of Thr and null, or (ii) Xaa 1 is selected from the group consisting of Cys, Thr and null; and Xaa 12 is Cys;

compound (II):

compound (III):

compound (IV):

or

compound (V):

wherein in (II)-(V) P 1 comprises a peptide having at least 85% homology with the peptide of SEQ ID NO:2, and is covalently bound through its N-amino terminus via an amide bond to the carbonyl group (1′);

whereby said peptide-containing moiety is resistant to phagocytosis in said subject.

22. The method of claim 21 , wherein said composition further comprises a solid particle, wherein said peptide-containing moiety is attached to said surface of said solid particle.

23. The method of claim 22 , wherein said solid particle is selected from the group consisting of a nanoparticle, vesicle, dendrimer, engineered cell, tissue fragment, implant, and combinations thereof.

24. The method of claim 22 , wherein said composition further comprises an agent selected from the group consisting of a therapeutic agent, imaging agent, radioactive agent, salt, protein, nucleic acid, gas and combinations thereof, wherein said agent is attached to or contained within said solid particle.

25. The method of claim 21 , wherein said composition further comprises a conjugated compound covalently linked to said peptide-containing moiety.

26. The method of claim 25 , wherein said conjugated compound is selected from the group consisting of a peptide, protein, nucleic acid, lipid, biologically active molecule, and combinations thereof.

27. A method of treating or ameliorating an inflammatory disease in a subject, comprising administering to said subject a pharmaceutical composition comprising a pharmaceutically effective amount of a peptide-containing moiety or a salt thereof, wherein said peptide-containing moiety comprises a compound selected from the group consisting of:

a peptide of SEQ ID NO:2, wherein: (i) Xaa 1 is Thr; and Xaa 12 is selected from the group consisting of Thr and null, or (ii) Xaa 1 is selected from the group consisting of Cys, Thr and null; and Xaa 12 is Cys;

compound (II):

compound (III):

compound (IV):

or

compound (V):

wherein in (II)-(V) P 1 comprises a peptide having at least 85% homology with the peptide of SEQ ID NO:2, and is covalently bound through its N-amino terminus via an amide bond to the carbonyl group (1′);

whereby administering said composition to said subject treats or ameliorates said inflammatory disease in said subject.

28. The method of claim 27 , wherein said composition further comprises a solid particle, wherein said peptide-containing moiety is attached to said surface of said solid particle.

29. The method of claim 28 , wherein said solid particle is selected from the group consisting of a nanoparticle, vesicle, dendrimer, engineered cell, tissue fragment, implant, and combinations thereof.

30. The method of claim 28 , wherein said composition further comprises an agent selected from the group consisting of a therapeutic agent, imaging agent, radioactive agent, salt, protein, nucleic acid, gas, and combinations thereof, wherein said agent is attached to or contained within said solid particle.

31. The method of claim 27 , wherein said composition further comprises a conjugated compound covalently linked to said peptide-containing moiety.

32. The method of claim 31 , wherein said conjugated compound is selected from the group consisting of a peptide, protein, nucleic acid, lipid, biologically active molecule, and combinations thereof.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 31, 2013
From: DISCHER, DENNIS E.
To: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Reel/Frame 031861/0283 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 31, 2013
From: RODRIGUEZ NUNEZ, PIA L.; PANTANO, DIEGO A.
To: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Reel/Frame 031861/0289 →
CONFIRMATORY LICENSE Recorded Dec 17, 2013
From: UNIVERSITY OF PENNSYLVANIA
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 031830/0617 →
Continuity (2)
Provisional Application 61440175 · Feb 7, 2011
Related Publication 20140140926A1 · May 22, 2014