ANTI-HEDGEHOG ANTIBODIES

• US 20100003239A1
• Filed: 12/22/2008
• Published: 01/07/2010
• Est. Priority Date: 12/28/2007
• Status: Active Grant

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Scales, Suzanna J.
• Granted Patent: US 8,030,454 B2
• Time in Patent Office: Days
• US Class Current: 424/130.1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: G01N 33/57419 of colon
• CPC Class Codes: G01N 33/57449 of ovaries
• CPC Class Codes: G01N 33/57496 involving intracellular compounds

Abstract

The invention relates to anti-hedgehog antibodies, their use in the detection of hedgehog expression in tissue, and to the use of such detection in the treatment of cancer.

Claims

1. An anti-hedgehog antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises the antigen binding regions HCHVR1, HCHVR2 and HCHVR3.

2. The anti-hedgehog antibody of claim 1 further comprising a light chain comprising the antigen binding regions LCHVR1, LCHVR2 and LCHVR3.

4. The anti-hedgehog antibody of claim 2 or 3 wherein the antibody is 95.9.

3. An anti-hedgehog antibody that binds hedgehog at an epitope within the region of amino acid residues 70-96.

5. A method of detecting hedgehog expression in tissue comprising detecting hedgehog expression in said tissue by contacting with an anti-hedgehog antibody and measuring the extent of binding, wherein said anti-hedgehog antibody binds to hedgehog at an epitope within the region of amino acid residues 70-96.

6. The method of claim 5, wherein the tissue is a tumor or cancer.

7. The method of claim 6, wherein the tissue is removed from the host prior to the determination.

8. The method of claim 7, wherein the tissue sample is FFPE prior to contacting with the anti-hedgehog antibody.

9. The method of claim 5, wherein the detection method is selected from the group consisting of IHC and Western blot.

10. The method of claim 5, wherein the binding specificity is greater than that of the anti-Hh antibody H160.

11. The method of claim 5, wherein the anti-hedgehog antibody does not compete with ptch for binding to shh.

12. The method of 11, wherein the anti-hedgehog antibody is 95.9.

13. A method for identifying tumors responsive to hedgehog antagonists, comprising contacting the tumor tissue or tissue proximal to the tumor with an anti-hedgehog antibody wherein said anti-hedgehog antibody binds to hedgehog polypeptide at an epitope within the region of amino acid residues 70-96 and determining if hedgehog is overexpressed in said tissue, compared to normal tissue.

14. The method of claim 13, wherein the tumor or tissue is removed from the host prior to the determination.

15. The method of claim 14, wherein the tissue sample is FFPE prior to contacting with the anti-hedgehog antibody.

16. The method of claim 13, wherein the determination method is selected from the group consisting of IHC and Western blot.

17. The method of claim 13 wherein the sensitivity of the anti-hedgehog antibody is greater that of the anti-hedgehog antibody H160.

18. The method of claim 13, wherein the antibody does not compete with patch for binding to Shh.

19. The method of claim 18, wherein the antibody is selected from the group consisting of 95.3, 95.7 and 95.9.

20. A method for treating cancer in a patient comprising:

(a) contacting a tumor and/or tissue proximal to the tumor removed from the patient with an anti-hedgehog antibody wherein said anti-hedgehog antibody binds to hedgehog polypeptide at an epitope within the region of amino acid residues 70-96,

(b) detecting the presence of hedgehog expression,

(c) comparing the hedgehog expression with that of normal or tissue of the same type or origin not associated with the tumor, and if such hedgehog is overexpressed,

(d) treating the patient with a hedgehog antagonist.

21. The method of claim 20, wherein the tissue is removed from the host prior to the determination.

22. The method of claim 21 wherein the tissue sample is FFPE prior the contacting with the anti-Hh antibody.

23. The method of claim 20 wherein the determination method is selected from the group consisting of:

of IHC and Western blot.

24. The method of claim 20 wherein the binding sensitivity is greater than that of the anti-Hh antibody H160.

25. The method of claim 20 wherein the anti-Hh antibody does not compete with ptch for binding to Shh.

26. The method of claim 25, wherein the anti-Hh antibody is selected from the group consisting of 95.3, 95.7 and 95.9.

27. An article of manufacture for measuring hedgehog expression, comprising an anti-hedgehog antibody wherein said anti-hedgehog antibody binds to hedgehog polypeptide at an epitope within the region of amino acid residues 70-96, and instructions for determining if hedgehog is overexpressed in a tissue, comprising contacting such tissue with such anti-hedgehog antibody and measuring the extent of binding.

28. The method of claim 27, wherein the tissue is a tumor or cancer.

29. The method of claim 27, wherein the tissue is removed from the host prior to the determination.

30. The method of claim 29, wherein the tissue sample is FFPE prior the contacting with the anti-Hh antibody.

31. The method of claim 27, wherein the determination method is selected from the group consisting of:

of IHC and Western blot.

32. The method of claim 27, wherein the binding sensitivity is greater than that of the anti-Hh antibody H160.

33. The method of claim 27, wherein the anti-Hh antibody does not compete with ptch for binding to Shh.

34. The method of claim 33, wherein the anti-Hh antibody is selected from the group consisting of 95.3, 95.7 and 95.9.

35. A method of screening patients with abnormal tissue growth for the risk of developing cancer, comprising determining if such tissue overexpresses hedgehog signaling with a hedgehog antibody wherein said anti-hedgehog antibody binds to hedgehog polypeptide at an epitope within the region of amino acid residues 70-96, comprising contacting such tissue with such anti-hedgehog antibody and measuring the extent of binding.

36. The method of claim 35, wherein the tissue is a tumor or cancer.

37. The method of claim 35, wherein the tissue is removed from the host prior to the determination.

38. The method of claim 37, wherein the tissue sample is FFPE prior to contacting with the anti-Hh antibody.

39. The method of claim 35, wherein the binding sensitivity is greater than that of the anti-Hh antibody H160.

40. The method of claim 35, wherein, the anti-Hh antibody does not compete with ptch for binding to Shh.

41. The method of claim 35, wherein the determination method is selected from the group consisting of IHC and Western Blot.

42. The method of claim 41, wherein the anti-Hh antibody is selected from the group consisting of 95.3, 95.7 and 95.9.

43. A method of treating cancer comprising (a) contacting tissue suspected of being cancerous or tissue proximal to such tissue with an anti-hedgehog antibody wherein said anti-hedgehog antibody binds to hedgehog polypeptide at an epitope within the region of amino acid residues 70-96;

(b) determining of hedgehog is overexpressed; and

(c) treating with a hedgehog antagonist.

44. The method of claim 43, wherein the tissue sample is removed from the host prior to the determination.

45. The method of claim 44, wherein the tissue sample is FFPE prior to contacting with the anti-Hh antibody.

46. The method of claim 43, wherein the determination method is selected from the group consisting of IHC and Western blot.

47. The method of claim 43, wherein the binding sensitivity of the anti-hedgehog antibody is greater than that of the anti-Hh antibody H160.

48. The method of claim 43, wherein the anti-Hh antibody does not compete with ptch for binding to Shh.

49. The method of claim 48, wherein the anti-Hh antibody is selected from the group consisting of 95.3, 95.7 and 95.9.