TREATMENT OF ABNORMAL OR EXCESSIVE SCARS

• US 20110130710A1
• Filed: 12/22/2008
• Published: 06/02/2011
• Est. Priority Date: 12/21/2007
• Status: Abandoned Application

• Current Assignee: Bradford James Duft, Colin Richard Green, David Lawrence Becker
• Original Assignee: Bradford James Duft, Colin Richard Green, David Lawrence Becker
• Inventors: Duft, Bradford James, Green, Colin Richard, Becker, David Lawrence
• Application Number:
  US12/809,916
• Publication Number:
  US 20110130710A1
• Time in Patent Office: Days
• US Class Current: 604/22
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics

Abstract

Methods, compounds, compositions, kits and articles of manufacture comprising anti-connexin polynucleotides for prevention and/or treatment of abnormal scars, including keloid scars, hypertrophic scars, atrophic scars, and widespread scars.

Claims

1. A method of treating a patient having an abnormal scar, which method comprises:

(a) excising the abnormal scar, and (b) administering an anti-connexin polynucleotide to the patient in a quantity sufficient to prevent or reduce abnormal scarring at the site of the excision.

2. The method of claim 1, wherein the anti-connexin polynucleotide decreases connexin protein expression, wherein said connexin is selected from the group consisting of connexin 26, connexin 30, connexin 30.3, connexin 31.1, connexin 32, connexin 36, connexin 37, connexin 40, connexin 40.1, connexin 43, connexin 45, connexin 46 and connexin 46.6.

3. The method of claim 2 wherein the anti-connexin polynucleotide is an antisense oligonucleotide.

4. A method according to claim 3 wherein the antisense oligonucleotide decreases expression of connexin 43.

5. The method of claim 2 wherein the anti-connexin polynucleotide is an siRNA oligonucleotide or an RNAi oligonucleotide.

6. A method according to claim 1, wherein the abnormal scar is present in or on the skin.

7. A method according to claim 1, wherein the abnormal scar is present in or on the eye.

8. A method according to claim 1 or 4, wherein the scar is a keloid scar.

9. A method according to claim 1 or 4, wherein the scar is a hypertrophic scar.

10. A method according to claim 1 or 4, wherein the scar is an atrophic scar.

11. A method according to claim 1 or 4, wherein the scar is a widespread scar.

12. A method according to claim 1, wherein the anti-connexin polynucleotide inhibits intercellular communication by decreasing gap junction formation.

13. A method according to claim 1, wherein the anti-connexin polynucleotide inhibits intercellular communication by decreasing connexin 43 gap junction formation.

14. A method according to claim 2, wherein the connexin is a human connexin.

15. A method according to claim 2, wherein the connexin is human connexin 43.

63. The method of any of claim 1, 16, 41 or 46, wherein the patient or subject is a human.

64. The method of any of claim 1, 16, 41 or 46, wherein the patient or subject is a non-human animal.

65. The method of claim 64, wherein the non-human animal is a sports or pet animal.

66. The method of claim 65, wherein the sports or pet animal is a horse, a dog or a cat.

16. A method of preventing or decreasing abnormal scar formation in a patient undergoing a surgical procedure, said method comprising administering a therapeutically effective amount of an anti-connexin polynucleotide to said patient.

17. A method according to claim 16 or wherein the anti-connexin polynucleotide is administered to an excision or incision.

18. A method according to claim 16 wherein the anti-connexin polynucleotide is administered to a debridement.

19. A method according to claim 16 wherein the anti-connexin polynucleotide is administered in the form of a liquid, gel, foam or spray.

20. A method according to claim 16 wherein said patient is at risk for keloid formation.

21. A method according to claim 16 wherein said patient is at risk for hypertrophic scar formation.

22. A method according to claim 16 wherein said patient is at risk for atrophic scar, or widespread scar formation.

23. A method according to claim 16, wherein the anti-connexin polynucleotide is an anti-connexin oligonucleotide.

24. A method according to claim 16 wherein the anti-connexin polynucleotide is oligonucleotide is selected from the group consisting of SEQ. I.D. NOS 1 to 12.

25. A method according to claim 16 wherein the connexin oligonucleotide is selected from SEQ. I.D. NOS. 1 and 2.

26. A method according to claim 16 wherein said anti-connexin polynucleotide is implanted or instilled.

27. A method according to any of claims 16-25 wherein the anti-connexin polynucleotide is an anti-connexin 43 compound.

28. A method according to claim 27 wherein said anti-connexin polynucleotide is administered topically.

29. A method to testing the activity of an anti-connexin polynucleotide for the prevention or reduction abnormal scarring, comprising contacting cells at risk of forming an abnormal scar with an anti-connexin polynucleotide, and determining or measuring the abnormal scarring prevention or reduction activity of said anti-connexin polynucleotide.

30. A method according to claim 29 wherein said method is carried out in vitro.

31. A method according to claim 29 wherein said method is carried out in vivo.

32. A method according to claim 29 wherein said method is carried out to test the activity of an anti-connexin polynucleotide to prevent or reduce keloid scar formation.

33. A method according to claim 29 wherein said method is carried out to test the activity of an anti-connexin polynucleotide to prevent or reduce hypertrophic scar formation.

34. A method according to claim 29 wherein said method is carried out to test the activity of an anti-connexin polynucleotide to prevent or reduce the formation of atrophic scars, or widespread scars.

35. A method according to claim 29 wherein said anti-connexin is an oligonucleotide.

36. An article of manufacture comprising:

(a) a pharmaceutical composition having (i) a therapeutically effective amount of an anti-connexin polynucleotide, and (ii) a pharmaceutically acceptable carrier, and (b) instructions for administering the pharmaceutical composition to a patient having or at risk of having an abnormal scar.

37. The article of claim 36 wherein the instructions describe administration of the pharmaceutical composition to the patient to treat an abnormal scar by excising the abnormal scar and administering the pharmaceutical composition in a quantity sufficient to prevent or reduce abnormal scarring at a site of the excision.

38. The article of claim 36 wherein the abnormal scar is selected from the group consisting of keloid scars, hypertrophic scars, atrophic scars, and widespread scars.

39. The article of claim 36 wherein the anti-connexin is an oligonucleotide.

40. The article of claim 39 wherein the oligonucleotide is an anti-connexin 43 oligonucleotide.

67. The article of manufacture of claim 36, wherein the patient is a human.

68. The article of manufacture of claim 36, wherein the patient is a non-human animal.

69. The article of manufacture of claim 68, wherein the non-human animal is a sports or pet animal.

70. The article of manufacture of claim 69, wherein the sports or pet animal is a horse, a dog or a cat.

41. A method of making an article of manufacture, which method comprises:

combining (a) a container including a pharmaceutical composition comprising (i) an anti-connexin polynucleotide, and (ii) a pharmaceutically acceptable carrier, and (b) labeling instructions for treating a patient having an abnormal scar by administering the pharmaceutical composition to a patient having an abnormal scar.

42. A method according to claim 41 wherein the instructions describe administration of the pharmaceutical composition to the patient to treat an abnormal scar by excising the abnormal scar and administering the pharmaceutical composition in a quantity sufficient to prevent or reduce abnormal scarring at a site of the excision.

43. A method according to claim 41 wherein the abnormal scar is selected from the group consisting of keloid scars, hypertrophic scars, atrophic scars, and widespread scars.

44. The article of claim 41 wherein the anti-connexin is an oligonucleotide.

45. The article of claim 44 wherein the oligonucleotide is an anti-connexin 43 oligonucleotide.

46. A method of decreasing or preventing excessive scar formation which comprises administration to a subject in need of treatment an effective amount of an anti-connexin polynucleotide.

47. A method according to claim 46 wherein the anti-connexin polynucleotide decreases connexin protein expression.

48. A method according to claim 47 wherein the connexin is selected from the group consisting of connexin 26, connexin 30, connexin 30.3, connexin 31.1, connexin 32, connexin 36, connexin 37, connexin 40, connexin 40.1, connexin 43, connexin 45, connexin 46 and connexin 46.6.

49. A method according to claim 48 wherein the connexin is connexin 43.

50. A method according to claim 47 wherein the anti-connexin polynucleotide is an antisense oligonucleotide.

51. A method according to claim 50 wherein the antisense oligonucleotide is anti-connexin 43 oligonucleotide.

52. A method according to claim 50 wherein the oligonucleotide has a sequence selected from SEQ. ID. NOS. 1 to 12.

53. A method according to claim 50 wherein the oligonucleotide has a sequence selected from SEQ. ID. NOS. 1 and 2.

54. A method according to any of claims 46-53 wherein the anti-connexin polynucleotide decreases or prevents keloid formation of keloid scars, hypertrophic scars, atrophic scars, or widespread scars.

55. A method according to claim 46 wherein the anti-connexin polynucleotide is implanted or instilled.

56. A method according to claim 55 wherein the anti-connexin polynucleotide is an anti-connexin 43 polynucleotide.

57. A method according to claim 56 wherein the anti-connexin 43 polynucleotide is an antisense oligonucleotide.

58. A method according to claim 57 wherein the antisense oligonucleotide is an anti-connexin 43 antisense oligonucleotide.

59. A method according to claim 46 wherein said anti-connexin polynucleotide is administered topically.

60. A method according to claim 59 wherein the anti-connexin polynucleotide is an anti-connexin 43 polynucleotide.

61. A method according to claim 60 wherein the anti-connexin 43 polynucleotide is an antisense oligonucleotide.

62. A method according to claim 61 wherein the antisense oligonucleotide is an anti-connexin 43 antisense oligonucleotide.