Hedgehog and patched antagonists for inhibiting cell and tissue growth and differentiation and uses therefor

• US 7,445,778 B2
• Filed: 03/12/2001
• Issued: 11/04/2008
• Est. Priority Date: 09/11/1998
• Status: Expired due to Fees

• Current Assignee: Curis, Inc.
• Original Assignee: Curis, Inc.
• Inventors: Burkly, Linda, Wang, Li Chun
• Primary Examiner(s): Ulm; John D
• Application Number:
  US09/804,490
• Publication Number:
  US 20020015702A1
• Time in Patent Office: 2,794 Days
• Field of Search: 530/388.22, 530/300, 530/350, 530/399, 514/2, 424/130.1, 424/178.1, 424/198.1, 436/501
• US Class Current: 424/145.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/46 Hybrid immunoglobulins hybrids of an immunoglobulin with a peptide not being an immunoglobulin C07K19/00
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C12N 2799/026 where the vector is derived from a baculovirus

Abstract

A method for inhibiting growth or differentiation of an epithelial cell comprising contacting at least an epithelial cell with an effective amount of an agent selected from the group consisting of a hedgehog antagonist and a patched antagonist.

Claims

1. A method for inhibiting growth or differentiation of an epithelial cell, comprising contacting at least an epithelial cell with an amount of an agent effective to inhibit at least one of the growth or differentiation of said epithelial cell, wherein said agent is an anti-hedgehog antibody, and wherein the anti-hedgehog antibody is selected from 5E1, a humanized anti-hedgehog antibody thereof, or fragments thereof.

2. The method of claim 1, wherein the anti-hedgehog antibody is a humanized anti-hedgehog antibody, or fragments thereof.

3. The method of claim 1, wherein the epithelial cell is a cutaneous epithelial cell.

4. The method of claim 1, wherein the epithelial cell is a mammalian epithelial cell.

5. The method of claim 1, wherein the epithelial cell is a dermal keratinocyte.

6. The method of claim 5, wherein the epithelial cell is a mammalian epithelial cell.

7. The method of claim 1, wherein the epithelial cell is a mucosal epithelial cell.

8. The method of claim 7, wherein the epithelial cell is a mammalian epithelial cell.

9. The method of claim 1, wherein the epithelial cell is an epitheial stem cell.

10. The method of claim 9, wherein the epithelial cell is a mammalian epithelial cell.

11. The method of claim 1, wherein the epithelial cell is a hair follicle stem cell.

12. The method of claim 1, wherein the anti-hedgehog antibody is 5E1.

13. The method of claim 1, wherein the epithelial cell is a mammalian epithelial cell.

14. A method for inhibiting growth of an epithelial tissue, comprising contacting at least the epithelial tissue with an amount of an agent effective to inhibit proliferation of at least the epithelial cells in the tissue, wherein the agent is an anti- hedgehog antibody, and wherein the anti-hedgehog antibody is selected from 5E1, a humanized anti-hedgehog antibody thereof, or fragments thereof.

15. The method of claim 14, wherein the anti-hedgehog antibody is a humanized anti-hedgehog antibody, or fragments thereof

16. The method of claim 14, wherein the epithelial tissue is an internal epithelial tissue.

17. The method of claim 16, wherein the internal epithelial tissue is intestinal lining.

18. The method of claim 17, wherein the epithelial tissue is mammalian tissue.

19. The method of claim 16, wherein the epithelial tissue is mammalian tissue.

20. The method of claim 16, wherein the epithelial tissue is vertebrate epithelial tissue.

21. The method of claim 14, wherein the epithelial tissue is mammalian tissue.

27. The method of claims 2, 15, or 23, wherein the anti-hedgehog antibody binds to a Sonic hedgehog protein.

22. A method for inhibiting growth of hair on an animal, comprising administering to the animal an amount of an agent effective to inhibit growth of hair on said animal, wherein the agent is an anti-hedgehog antibody, which anti-hedgehog antibody inhibits proliferation of hair follicle keratinocytes, and wherein the anti-hedgehog antibody is selected from 5E1, a humanized anti-hedgehog antibody thereof, or fragments thereof.

23. The method of claim 22, wherein the anti-hedgehog antibody is a humanized anti-hedgehog antibody, or fragments thereof

24. The method of claim 22, wherein the anti-hedgehog antibody is 5E1.

25. The method of claim 22, wherein the anti-hedgehog antibody affects the anagen phase of the hair growth cycle.

26. The method of claim 22, wherein administering comprises topically administering.

28. A method for inhibiting the proliferation of hair follicle cells, comprising topically contacting the cells with an amount of an agent effective to decrease the proliferation of the hair follicle cells, wherein the agent is an anti-Sonic hedgehog antibody, a humanized anti-Sonic hedgehog antibody thereof, or fragments thereof.

29. The method of claim 28, wherein the anti-hedgehog antibody is 5E1.

30. The method of claim. 28, wherein the anti-hedgehog antibody affects the anagen phase of the hair growth cycle.

31. A method for inhibiting growth or differentiation of an epithelial cell, comprising contacting at least an epithelial cell with an amount of an agent effective to inhibit at least one of the growth or differentiation of said. epithelial cell, wherein said agent is an anti-Sonic hedgehog antibody, a humanized anti-Sonic hedgehog antibody thereof, or fragments thereof.

32. The method of claim 31, wherein the epithelial cell is a cutaneous epithelial cell.

33. The method of claim 32, wherein the epithelial cell is a mammalian epithelial cell.

34. The method of claim 31, wherein the epithelial cell is a dermal keratinocyte.

35. The method of claim 34, wherein the epithelial cell is a mammalian epithelial cell.

36. The method of claim 31, wherein the epithelial cell is a mucosal epithelial cell.

37. The method of claim 36, wherein the epithelial cell is a mammalian epithelial cell.

38. The method of claim 31, wherein the epithelial cell is an epithelial stem cell.

39. The method of claim 38, wherein the epithelial cell is a mammalian epithelial cell.

40. The method of claim 31, wherein the epithelial cell is a hair follicle stem cell.

41. The method of claim 31, wherein the epithelial cell is an internal epithelial cell.

42. The method of claim 41, wherein the epithelial cell is a mammalian epithelial cell.

43. The method of claim 41, wherein the epithelial cell is a vertebrate epithelial cell.

44. The method of claim 31, wherein the epithelial cell is a mammalian epithelial cell.

45. A method for inhibiting growth of an epithelial tissue, comprising topically contacting at least the epithelial tissue with an amount of an agent effective to inhibit proliferation of at least the epithelial cells in the tissue, wherein the agent is an anti Sonic-hedgehog antibody, a humanized anti-Sonic hedgehog antibody thereof, or fragments thereof.

46. The method of claim 45, wherein the epithelial tissue is mammalian, tissue.

47. A method for inhibiting growth of hair on an animal, comprising administering to the animal an amount of an agent effective to inhibit growth of hair on said animal, which agent inhibits proliferation of hair follicle keratinocytes, wherein the agent is an anti-Sonic hedgehog antibody, a humanized anti-Sonic hedgehog antibody thereof, or fragments thereof.

48. A method for inhibiting growth or differentiation of a hair follicle stem cell, comprising contacting said cell with an amount of an agent effective to inhibit at least one of the growth or differentiation of said cell, wherein said agent is an anti-hedgehog antibody, and wherein the anti-hedgehog antibody is selected from 5E1, a humanized anti-hedgehog antibody thereof, or fragments thereof.

49. A method for inhibiting the proliferation of hair follicle cells, comprising topically contacting the cells with an amount of an agent effective to decrease the proliferation of the hair follicle cells, wherein the agent is an anti-hedgehog antibody selected from 5E1, a humanized anti-hedgehog antibody thereof, or fragments thereof.

50. A method for inhibiting growth of hair on an animal, comprising administering to the animal an amount of an agent effective to inhibit growth of hair on said animal, wherein the agent is an anti-hedgehog antibody, which anti-hedgehog antibody inhibits proliferation of hair follicle keratinocytes, and wherein the anti-hedgehog antibody is selected from an anti-Sonic hedgehog antibody, a humanized anti-Sonic hedgehog antibody thereof, or fragments thereof.

51. The method of claim 50, wherein administering comprises topically administering.

52. A method for inhibiting the proliferation of hair follicle cells, comprising topically contacting the cells with an amount of an agent effective to decrease the proliferation of the hair follicle cells, wherein the agent is an anti-hedgehog antibody selected from an anti-Sonic hedgehog antibody, a humanized anti-Sonic hedgehog antibody thereof, or fragments thereof.