Aptamer-modified polymeric materials for the binding of factors in a wound environment

Patent metadata

Field	Value
Publication number	US-9382290-B2
Application number	US-201213458071-A
Country	US
Kind code	B2
Filing date	Apr 27, 2012
Priority date	Apr 29, 2011
Publication date	Jul 5, 2016
Grant date	Jul 5, 2016

Abstract

The present invention provides aptamer-modified polymers and materials thereof, which may be used for the binding of factors in a wound bed. For example, the aptamer-modified materials can be polypeptides conjugated to polymer foam materials. Such materials may be used, for example, for dressings, wound inserts, or pads.

First claim

What is claimed is:

1. A wound dressing comprising a polyurethane foam substrate, wherein the polyurethane foam substrate comprises a co-polymer, and wherein the co-polymer comprises:
a polymer polymerized with an amino sugar, or
a polymer polymerized with an aminoglycoside,
wherein an aptamer is covalently attached directly or via one or more linkers to a repeat unit of the co-polymer, and wherein the aptamer is a polypeptide having a sequence at least 90% identical to SEQ ID NO:1 or at least 90% identical to SEQ ID NO:2.

2. The wound dressing of claim 1 , wherein the amino sugar is chitosan or glucosamine.

3. The wound dressing of claim 1 , wherein the aminoglycoside is selected from the group consisting of neomycin, dibekacin, kanamycin, tobramycin, streptomycin, and gentamicin.

4. The wound dressing of claim 1 , wherein the polymer foam substrate is a reticulated open-celled foam.

5. The wound dressing of claim 1 , wherein the polymer foam substrate further comprises a substituted silyl-derived linker.

6. The wound dressing of claim 1 , wherein the polypeptide is modified with an amino or carboxyl terminal Cys (Cysteine) residue.

7. The wound dressing of claim 1 , wherein the polypeptide is modified with the linker AEEAc-Cys-NH 2 at the amino or carboxyl terminus, wherein AEEAc is [2-(2-aminoethoxy)ethoxy]acetic acid.

8. The wound dressing of claim 1 , wherein the amino or carboxyl terminus of the polypeptide is modified with a polyethylene glycol (PEG) spacer-cysteine residue.

9. The wound dressing of claim 1 , wherein the aptamer is covalently attached to the polymer foam substrate through one or more linkers.

10. The wound dressing of claim 9 , wherein the aptamer is covalently attached to the one or more linkers through a thioether linkage.

11. The wound dressing of claim 9 , wherein the linker is an N-(e-Maleimidocaproyloxy) sulfosuccinimide ester-derived linker (EMCS-derived linker) or a sulfo-EMCS-derived linker.

12. The wound dressing of claim 9 , wherein the linker is a substituted silyl-derived linker.

13. The wound dressing of claim 12 , wherein the substituted silyl-derived linker is derived from aminoundecyltriethoxysilane or aminopropyldiisopropylethoxysilane.

14. The wound dressing of claim 1 , wherein the aptamer is a polypeptide having a sequence at least 90% identical to SEQ ID NO: 1.

15. The wound dressing of claim 14 , wherein the polypeptide is modified with an amino or carboxyl terminal Cys residue.

16. The wound dressing of claim 14 , wherein the polypeptide is modified with the linker AEEAc-Cys-NH 2 at the amino or carboxyl terminus.

17. The wound dressing of claim 14 , wherein the amino or carboxyl terminus of the polypeptide is modified with a polyethylene glycol (PEG) spacer-cysteine residue.

18. The wound dressing of claim 14 , wherein the polypeptide is covalently attached to the polymer foam substrate through one or more linkers.

19. The wound dressing of claim 18 , wherein the polypeptide is covalently attached to the one or more linkers through a thioether linkage.

20. The wound dressing of claim 18 , wherein the linker is an N-(e-Maleimidocaproyloxy) sulfosuccinimide ester-derived linker (EMCS-derived linker) or a sulfo-EMCS-derived linker.

21. The wound dressing of claim 18 , wherein the linker is a substituted silyl-derived linker.

22. The wound dressing of claim 21 , wherein the substituted silyl-derived linker is derived from aminoundecyltriethoxysilane or aminopropyldiisopropylethoxysilane.

23. The wound dressing of claim 14 , wherein the wound dressing further comprises a granulocyte macrophage colony stimulating factor (GM-CSF).

24. The wound dressing of claim 1 , wherein the polypeptide comprises a sequence at least 90% identical to SEQ ID NO: 2.

25. The wound dressing of claim 24 , wherein the polypeptide is modified with an amino or carboxyl terminal Cys residue.

26. The wound dressing of claim 24 , wherein the polypeptide is modified with the sequence AEEAc-Cys-NH 2 at the amino or carboxyl terminus.

27. The wound dressing of claim 24 , wherein the amino or carboxyl terminus of the polypeptide is modified with a polyethylene glycol (PEG) spacer-cysteine residue.

28. The wound dressing of claim 24 , wherein the polypeptide is covalently attached to the polymer foam substrate through one or more linkers.

29. The wound dressing of claim 28 , wherein the polypeptide is covalently attached to the one or more linkers through a thioether linkage.

30. The wound dressing of claim 28 , wherein the linker is an N-(e-Maleimidocaproyloxy) sulfosuccinimide ester-derived linker (EMCS-derived linker) or a sulfo-EMCS-derived linker.

31. The wound dressing of claim 28 , wherein the linker is a substituted silyl-derived linker.

32. The wound dressing of claim 31 , wherein the substituted silyl-derived linker is derived from aminoundecyltriethoxysilane or aminopropyldiisopropylethoxysilane.

33. The wound dressing of claim 24 , wherein the wound dressing further comprises a vascular endothelial growth factor (VEGF).

34. The wound dressing of claim 1 , wherein the aptamer is P16.

35. The wound dressing of claim 1 , wherein the aptamer is P22.

36. The wound dressing of claim 1 , wherein the polypeptide has the sequence of SEQ ID NO: 2.

37. A method for treating a wound comprising contacting a wound site with a wound dressing of claim 1 .

38. The method of claim 37 , wherein the method further comprises applying negative pressure to the wound site.

39. The method of claim 38 , wherein the method further comprises applying wound instillation solution to the wound site.

40. A method for binding a growth factor, chemokine or cytokine comprising contacting a fluid comprising the growth factor, chemokine, or cytokine with a wound dressing of claim 1 , thereby binding the growth factor, chemokine, or cytokine to the wound dressing.

41. The method of claim 40 , further comprising contacting the wound dressing with at least a second fluid, wherein some or all of the growth factor, chemokine, or cytokine bound to the wound dressing is eluted into the second fluid.

Assignees

• Courage James
• Allen Diwi
• Mcnulty Amy
• Rycerz Anthony
• Carroll Christopher
• HANSON Douglas
• Fruchterman Todd
• Kci Licensing Inc

Inventors

• Courage James
• Allen Diwi
• Mcnulty Amy
• Rycerz Anthony
• Carroll Christopher
• HANSON Douglas
• Fruchterman Todd

Classifications

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title

• A61L15/44 Primary

  Medicaments · CPC title

• C07K14/78

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] · CPC title

• A61L2430/34

  for soft tissue reconstruction · CPC title

• A61L15/26

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof {(A61L15/225 takes precedence)} · CPC title