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

• US 20020015702A1
• Filed: 03/12/2001
• Published: 02/07/2002
• Est. Priority Date: 09/11/1998
• Status: Active Grant

• Current Assignee: Curis, Inc.
• Original Assignee: Curis, Inc.
• Inventors: Burkly, Linda, Wang, Li Chun
• Granted Patent: US 7,445,778 B2
• Time in Patent Office: Days
• US Class Current: 424/142.1
• 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 effective amount of an agent selected from the group consisting of a hedgehog antagonist and a patched antagonist.

2. The method of claim 1, wherein the hedgehog antagonist is an anti-hedgehog antibody homolog selected from the group consisting of a human antibody, a chimeric antibody, a humanized antibody and fragments thereof.

3. The method of claim 1, wherein the patched antagonist is an anti-patched antibody homolog selected from the group consisting of a human antibody, a chimeric antibody, a humanized antibody and fragments thereof.

4. The method of claim 1, wherein the hedgehog antagonist is a hedgehog mutant that binds to a hedgehog receptor but does not elicit hedgehog-mediated signaling.

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

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

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

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

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

18. The method of claim 1, wherein the cell is treated in an animal and the agent is administered to the animal as a therapeutic composition.

20. The method of claims 1 or 5, wherein the agent is applied topically.

5. 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 selected from the group consisting of a hedgehog antagonist and a patched antagonist.

6. The method of claim 5, wherein the hedgehog antagonist is an anti-hedgehog antibody homolog selected from the group consisting of a human antibody, a chimeric antibody, a humanized antibody and fragments thereof.

7. The method of claim 5, wherein the patched antagonist is an anti-patched antibody homolog selected from the group consisting of a human antibody, a chimeric antibody, a humanized antibody and fragments thereof

8. The method of claim 5, wherein the hedgehog antagonist is a hedgehog mutant that binds to a hedgehog receptor but does not elicit hedgehog-mediated signaling.

19. The method of claim 5, wherein the epithelial tissue is treated in an animal and the agent is administered to the animal as a therapeutic composition.

9. A method for inhibiting growth of hair on an animal, comprising treating the animal with an amount of an agent effective to inhibit growth of hair, wherein the agent is selected from the group consisting of a hedgehog antagonist and a patched antagonist which inhibit proliferation of hair follicle keratinocytes.

10. The method of claim 9, wherein the hedgehog antagonist is an anti-hedgehog antibody homolog selected from the group consisting of a human antibody, a chimeric antibody, a humanized antibody and fragments thereof.

11. The method of claim 9, wherein the patched antagonist is an anti-patched antibody homolog selected from the group consisting of a human antibody, a chimeric antibody, a humanized antibody and fragments thereof

12. The method of claim 9, wherein the hedgehog antagonist is a hedgehog mutant that binds to a hedgehog receptor but does not elicit hedgehog-mediated signaling.

21. The method of claims 2, 6, or 10, wherein the anti-hedgehog antibody homolog is an antibody homolog that binds to a Sonic hedgehog protein.

22. The method of claims 2, 6, or 10, wherein the anti-hedgehog antibody homolog is an antibody homolog that binds to an Indian hedgehog protein.

23. The method of claims 2, 6, or 10, wherein the anti-hedgehog antibody homolog is an antibody homolog that binds to a Desert hedgehog protein.

25. The method of claim 24, wherein the hedgehog antagonist is an anti-hedgehog antibody selected from the group consisting of a human antibody, a chimeric antibody, a humanized antibody and fragments thereof.

26. The method of claim 24, wherein the patched antagonist is an anti-patched antibody homolog selected from the group consisting of a human antibody, a chimeric antibody, a humanized antibody and fragments thereof

27. The method of claim 24, wherein the hedgehog antagonist is a hedgehog mutant that binds to a hedgehog receptor but does not elicit hedgehog-mediated signaling.

29. The preparation of claim 28, wherein the antibody is selected from the group consisting of a human antibody, a chimeric antibody, a humanized antibody and fragments thereof.

24. A method for inhibiting the proliferation of hair follicle cells, comprising contacting the cells with a hedgehog antagonist or a patched antagonist in an amount effective to decrease the proliferation of the hair follicle cells

28. A preparation of an anti-hedgehog antibody homolog or anti-patched antibody homolog formulated for topical application to epithelial tissue.