Medicaments and proteins based on TGF-β monomers for the treatment of wounds

• US 7,902,150 B2
• Filed: 03/12/2007
• Issued: 03/08/2011
• Est. Priority Date: 03/11/2006
• Status: Expired due to Fees

• Current Assignee: Renovo Ltd. (Bentley Park Ltd.)
• Original Assignee: Renovo Ltd. (Bentley Park Ltd.)
• Inventors: Ferguson, Mark William James, Occleston, Nick, Mellors, Phillip, Atkinson, Emma, O'Kane, Sharon, Laverty, Hugh Gerard
• Primary Examiner(s): Kemmerer; Elizabeth C.
• Application Number:
  US12/282,472
• Publication Number:
  US 20090137475A1
• Time in Patent Office: 1,457 Days
• Field of Search: None
• US Class Current: 514/8.9
• 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. A method of accelerating wound healing, the method comprising administering to a patient in need of such treatment a therapeutically effective amount of a monomeric wild-type TGF-β

3 or a biologically active fragment thereof to accelerate healing of a wound.

2. A method according to claim 1, wherein the monomeric wild-type TGF-β

3 is administered and the monomeric wild-type TGF-β

3 has an amino acid sequence comprising Sequence ID No. 3.

3. A method according to claim 1 wherein the wound is a dermal wound.

4. A method according to claim 1 wherein the wound is an acute wound.

5. A method according to claim 1 wherein the wound is a burn.

6. A method according to claim 1 wherein the wound is a chronic wound.

19. A method according to claim 1, wherein 50-200 ng of the monomeric wild-type TGF-β

3 or biologically active fragment thereof/linear cm of wound is administered.

20. A method according to claim 1, wherein 100-300 ng of the monomeric wild-type TGF-β

3 or biologically active fragment thereof/linear cm of wound is administered.

27. A method according to claim 1, wherein the TGF-β

3 or biologically active fragment thereof is administered (a) immediately prior to formation of a wound and (b) again 24 hours after wounding.

28. A method according to claim 1, wherein the TGF-β

3 or biologically active fragment thereof is administered once a day for up to 3 days.

29. A method according to claim 1, wherein the TGF-β

3 or biologically active fragment thereof is administered immediately prior to the forming of the wound.

30. The method according to claim 1, wherein the biologically active fragment of TGF-β

3 comprises the receptor-binding portion of TGF-β

3.

31. The method according to claim 1, wherein the biologically active fragment of TGF-β

3 has wound healing activity in a rat model of cutaneous wound healing.

7. A method for promoting epithelial regeneration while inhibiting scarring, the method comprising administering to a patient in need thereof a therapeutically effective amount of a monomeric wild-type TGF-β

3 or a biologically active fragment thereof to promote epithelial regeneration and inhibit scarring.

8. A method according to claim 7 wherein the epithelial regeneration occurs at a site of damaged epithelium.

9. A method according to claim 8 wherein the epithelia is epidermis.

16. A method according to claim 7, wherein wild type TGF-β

3 monomer having an amino acid sequence comprising Sequence ID No. 3 is administered.

21. A method according to claim 7, wherein 50-200 ng of the monomeric wild-type TGF-β

3 or biologically active fragment thereof/cm² of epithelial damage is administered.

22. A method according to claim 7, wherein 100-300 ng of the monomeric wild-type TGF-β

3 or biologically active fragment thereof/cm² of epithelial damage is administered.

10. A method of inhibiting scarring, the method comprising administering to a patient in need of such treatment a therapeutically effective amount of a monomeric wild-type TGF-β

3 or a biologically active fragment thereof to inhibit scarring.

11. A method according to claim 10, wherein wild-type TGF-β

3 monomer having an amino acid sequence comprising Sequence ID No. 3 is administered.

12. A method according to claim 10 wherein the inhibition of scarring is effected at the dermis.

13. A method according to claim 10 inhibition of scarring is effected at the site of an acute wound.

14. A method according to claim 13 wherein the wound is a burn.

15. A method according to claim 10 wherein the inhibition of scarring is effected at the site of a chronic wound.

23. A method according to claim 10, wherein 50-200 ng of the monomeric wild-type TGF-β

3 or biologically active fragment thereof/linear cm of wound is administered.

24. A method according to claim 10, wherein 100-300 ng of the monomeric wild-type TGF-β

3 or biologically active fragment thereof/linear cm of wound is administered.

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

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

18. A method according to claim 17, wherein wild-type TGF-β

3 monomer having an amino acid sequence comprising Sequence ID No. 3 is administered.

25. A method according to claim 17, wherein 50-200 ng of the monomeric wild-type TGF-β

3 or biologically active fragment thereof/linear cm of wound is administered.

26. A method according to claim 17, wherein 100-300 ng monomeric of the wild-type TGF-β

3 or biologically active fragment thereof/linear cm of wound is administered.

32. A method of accelerating wound healing, the method comprising administering by injection to a patient in need thereof 50-200 ng of monomeric wild-type TGF-β

3 /linear cm of wound immediately prior to the forming of a wound to accelerate healing of the wound.

33. A method for promoting epithelial regeneration while inhibiting scarring, the method comprising administering by injection to a patient in need thereof 50-200 ng of monomeric wild-type TGF-β

3/cm² of epithelial damage immediately prior to the forming of a wound to the patient to promote epithelial regeneration and inhibit scarring.

34. A method of inhibiting scarring, the method comprising administering by injection to a patient in need thereof 50-200 ng of monomeric wild-type TGF-β

3/cm² of epithelial damage immediately prior to the forming of a wound to the patient to inhibit scarring.

35. A method of accelerating wound healing, the method comprising administering by injection to a patient in need thereof (a) immediately prior to formation of a wound and (b) again 24 hours after wounding, a therapeutically effective amount of monomeric wild-type TGF-β

3 to accelerate healing of the wound.

36. A method for promoting epithelial regeneration while inhibiting scarring, the method comprising administering by injection to a patient in need thereof (a) immediately prior to formation of a wound and (b) again 24 hours after wounding, a therapeutically effective amount of monomeric wild-type TGF-β

3 to promote epithelial regeneration and inhibit scarring.

37. A method of inhibiting scarring, the method comprising administering by injection to a patient in need thereof (a) immediately prior to formation of a wound and (b) again 24 hours after wounding, a therapeutically effective amount of monomeric wild-type TGF-β

3 to inhibit scarring.