MEDICAMENTS AND PROTEINS BASED ON TGF-BETA MONOMERS FOR THE TREATMENT OF WOUNDS

• US 20090137475A1
• Filed: 03/12/2007
• Published: 05/28/2009
• Est. Priority Date: 03/11/2006
• Status: Active Grant

• Current Assignee: Renovo Ltd. (Bentley Park Ltd.)
• Original Assignee: Renovo Ltd. (Bentley Park Ltd.)
• Inventors: Ferguson, Mark William James, Occleston, Nick, Atkinson, Emma, O'Kane, Sharon, Laverty, Hugh Gerard, Mellor, Phillip
• Granted Patent: US 7,902,150 B2
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 38/1841 Transforming growth factor [TGF]
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

There is provided the use of monomeric TGF-βs, or there fragments or derivatives, as medicaments. These medicaments preferably comprise monomeric TGF-β3, or fragments or derivatives thereof. The medicaments provided may be used in the acceleration of wounding and/or the inhibition of scarring, in the promotion of epithelial regeneration, or in the prevention and/or treatment of fibrotic disorders.

Claims

1-19. -19. (canceled)

20. A method of accelerating wound healing or inhibiting scarring, the method comprising administering to a patient in need of such treatment a therapeutically effective amount of a monomeric TGF-β

or a biologically active fragment or derivative thereof to accelerate healing of a wound or inhibit scarring.

21. A method according to claim 20, wherein the TGF-β

monomer, or biologically active fragment or derivative thereof, is a wild type TGF-β

3 monomer comprising Sequence ID No. 3, or a biologically active fragment or derivative thereof.

22. A method according to claim 20 wherein the wound is a dermal wound.

23. A method according to claim 20 wherein the wound is an eye wound.

24. A method according to claim 20 wherein the wound is an acute wound.

25. A method according to claim 20 wherein the wound is a burn.

26. A method according to claim 20 wherein the wound is a chronic wound.

34. A composition comprising a TGF-β

monomer, or a biologically active fragment or derivative thereof, and a pharmaceutically acceptable vehicle.

27. A method for promoting epithelial regeneration, the method comprising administering to a patient in need thereof a therapeutically effective amount of the composition of claim 34 to promote epithelial regeneration.

28. A method according to claim 27 wherein the epithelial regeneration occurs at a site of damaged epithelium.

29. A method according to claim 28 wherein the epithelium is epidermis.

30. A method according to claim 28 wherein the epithelium is an epithelium of the eye.

31. A method for preventing or treating a fibrotic disorder, the method comprising administering to a patient in need thereof a therapeutically effective amount of the composition of claim 34.

32. A method according to claim 31, wherein the fibrotic disorder is selected from the group consisting of lung fibrosis, liver fibrosis, scleroderma, skin fibrosis, muscle fibrosis, radiation fibrosis, kidney fibrosis, ocular fibrosis, and uterine fibrosis.

35. The composition of claim 34 wherein the TGF-β

monomer has a molecular weight of approximately 12 kDa.

36. The composition of claim 34 wherein the TGF-β

monomer is selected from the group consisting of Sequence ID No. 1, Sequence ID No. 2, and Sequence ID No. 3.

37. The composition of claim 34 wherein the TGF-β

monomer, or biologically active fragment or derivative thereof, is a TGF-β

3 monomer comprising Sequence ID No. 3 or a biologically active fragment or derivative thereof.

38. The composition of claim 34 wherein the TGF-β

monomer, or biologically active fragment or derivative thereof, is provided at a concentration of between 0.79 pM and 0.79 mM.

39. The composition of claim 34 wherein the composition is substantially free from alcohol.

40. The composition of claim 34 wherein the TGF-β

monomer, or biologically active fragment or derivative thereof, is folded into its biologically active form by a method comprising adding solubilised, unfolded monomeric TGF-β

, or fragment or derivative thereof, to a solution containing;

(i) 2-(cyclohexylamino)-ethanesulfonic acid (CHES) or a functional analogue thereof; and

(ii) a low molecular weight sulfhydryl/disulfide redox system; and

incubating the TGF-β

in the solution until a biologically active monomeric TGF-β

is formed.