Interleukin-10 compositions for the treatment of adenocarcinomas

• US 7,939,056 B2
• Filed: 11/13/2006
• Issued: 05/10/2011
• Est. Priority Date: 11/14/2005
• Status: Active Grant

• Current Assignee: Brigham and Women's Hospital Incorporated, Massachusetts Institute of Technology
• Original Assignee: Brigham and Women's Hospital Incorporated
• Inventors: Erdman, Susan, Fox, James, Davidson, Anne, Horwitz, Bruce
• Primary Examiner(s): Kemmerer; Elizabeth C.
• Assistant Examiner(s): Xie; Xiaozhen
• Application Number:
  US11/598,002
• Publication Number:
  US 20070122383A1
• Time in Patent Office: 1,639 Days
• Field of Search: None
• US Class Current: 424/85.1
• CPC Class Codes: A61K 38/2066 IL-10

Abstract

The present invention is directed to methods for the treatment of adenocarcinomas that are characterized by the overexpression of a particular oncogene, Pim-1. The procedure involves administering a therapeutically effective amount of interleukin-10 that has been coupled to a carrier that increases its circulating plasma half-life.

Claims

1. A method of treating a patient for an adenocarcinoma of the colon which does not occur subsequent to an inflammatory bowel disease and which overexpresses the Pim-1 oncogene, comprising administering to said patient an effective amount of a chimeric protein in which human IL10 is fused to the Fc region of a human IgG and wherein said chimeric protein has a circulating plasma half-life that is at least twice as long as free human IL10.

2. The method of claim 1, wherein said human IgG is human IgG2a.

3. The method of claim 1, wherein said chimeric protein further comprises the hinge region of IgG and said IL10 is fused to said hinge region.

4. The method of claim 1, wherein said chimeric protein has a circulating plasma half-life of at least four hours.

5. The method of claim 1, wherein said chimeric protein is administered to said patient by injection or infusion at a dose of 0.5 μ

g/kg body weight to 50 μ

g/kg body weight.

6. The method of claim 1, wherein said Fc region of said human IgG is non-lytic.

7. The method of claim 1, wherein said chimeric protein is administered to said patient by injection or infusion at a dose of 0.5-5 mg.

8. The method of claim 1, wherein:

a) said human IgG is human IgG2a;

b) said chimeric protein further comprises the hinge region of IgG and said IL10 is fused to said hinge region; and

c) said chimeric protein has a circulating plasma half-life of at least four hours.

9. The method of claim 8, wherein said Fc region of said human IgG is non-lytic.

10. The method of claim 9, wherein said chimeric protein is administered to said patient by injection or infusion at a dose of 0.5-5 mg.

11. A method of treating a patient for an adenocarcinoma of the colon which does not occur subsequent to an inflammatory bowel disease, comprising:

a) assaying a biological sample from said patient to determine if said adenocarcinoma is producing more Pim-1 oncogene than the amount produced by normal tissue of the same organ; and

b) if the results of the assay of step a) indicate that said adenocarcinoma is producing greater than normal amounts of said Pim-1 oncogene, administering to said patient a pharmaceutical composition comprising an effective amount of a chimeric protein in which human IL10 is fused to the Fc region of a human IgG and wherein said chimeric protein has a circulating plasma half-life that is at least twice as long as free human IL10.

12. The method of claim 11, wherein said chimeric protein has a circulating plasma half-life of at least four hours.

13. The method of claim 12, wherein said chimeric protein is administered at a dosage of between 0.5 μ

g/kg body weight and 50 μ

g/kg body weight.

14. The method of claim 11, wherein said human IgG is human IgG2a.

15. The method of claim 14, wherein said chimeric protein further comprises the hinge region of IgG and said IL10 is fused to said hinge region.

16. The method of claim 15, wherein said Fc region of said human IgG is non-lytic.

17. The method of claim 16, wherein said chimeric protein has a circulating plasma half-life of at least four hours.

18. The method of claim 17, wherein said chimeric protein is administered to said patient by injection or infusion at a dose of 0.5 μ

g/kg body weight to 50 μ

g/kg body weight.

19. The method of claim 18, wherein said chimeric protein is administered to said patient by injection or infusion at a dose of 0.5-5 mg.

20. The method of claim 18, wherein the assay of step a) is an ELISA assay.