Methods for treating cancer by achieving therapeutically effective doses of anti-CD47 antibody

Patent metadata

Field	Value
Publication number	US-11603404-B2
Application number	US-202217734904-A
Country	US
Kind code	B2
Filing date	May 2, 2022
Priority date	Mar 15, 2013
Publication date	Mar 14, 2023
Grant date	Mar 14, 2023

Abstract

Methods are provided for treating a subject with a therapeutic dose of anti-CD47 agent by administering a primer agent prior to administering a therapeutically effective dose of an anti-CD47 agent to the subject.

First claim

What is claimed is:

1. A method for treating acute myeloid leukemia (AML) in a human subject, the method comprising:
(a) administering a sub-therapeutic dose of an anti-CD47 antibody or a fragment thereof to the subject, wherein the sub-therapeutic dose is capable of increasing production of reticulocytes; and
(b) administering a therapeutically effective dose of the anti-CD47 antibody or the fragment thereof to the subject,
wherein the anti-CD47 antibody or the fragment thereof blocks an interaction between CD47 and SIRPα.

2. The method according to claim 1 , wherein the sub-therapeutic dose is administered at a dose from 0.05 mg/kg to 7.5 mg/kg.

3. The method according to claim 1 , wherein the sub-therapeutic dose is administered at a dose from 0.05 mg/kg to 5 mg/kg.

4. The method according to claim 1 , wherein the sub-therapeutic dose is administered at a dose from 0.1 mg/kg to 7.5 mg/kg.

5. The method according to claim 1 , wherein the sub-therapeutic dose is administered at a dose from 0.1 mg/kg to 5 mg/kg.

6. The method according to claim 1 , wherein the sub-therapeutic dose is administered at a dose from 1 mg/kg to 7.5 mg/kg.

7. The method according to claim 1 , wherein the sub-therapeutic dose is administered at a dose from 1 mg/kg to 5 mg/kg.

8. The method according to claim 1 , wherein the sub-therapeutic dose is administered at a dose of 1 mg/kg.

9. The method according to claim 1 , wherein the therapeutically effective dose is administered at a dose from 10 mg/kg to 40 mg/kg.

10. The method according to claim 1 , wherein the therapeutically effective dose is administered at a dose of 30 mg/kg.

11. The method according to claim 1 , wherein step (b) is performed in a range from 3 days to 21 days after beginning the administering of the sub-therapeutic dose.

12. The method according to claim 1 , wherein the sub-therapeutic dose increases the production of the reticulocytes.

13. The method according to claim 1 , wherein in step (a), the sub-therapeutic dose is determined to be effective by measuring in a blood sample from the human subject at least one of: an increase in an absolute or relative number of reticulocytes, an increase in a level of erythropoietin, and a decrease in a level of hemoglobin levels.

14. The method of claim 13 , wherein a reticulocyte count is at least 400×10 9 reticulocytes per liter (L).

15. The method of claim 1 , wherein step (b) comprises administering the anti-CD47 antibody or the fragment thereof in two or more doses of escalating concentration until a therapeutically effective dose is administered.

16. The method according to claim 1 , wherein step (b) comprises administering two or more therapeutically effective doses.

17. The method of claim 1 , wherein the anti-CD47 antibody is a monoclonal antibody.

18. The method of claim 1 , wherein the anti-CD47 antibody is a humanized antibody or a chimeric antibody.

19. A method for treating a hematological cancer in a human subject, the method comprising:
(a) administering a sub-therapeutic dose of an anti-CD47 antibody or a fragment thereof to the subject, wherein the sub-therapeutic dose is capable of increasing production of reticulocytes; and
(b) administering a therapeutically effective dose of the anti-CD47 antibody or the fragment thereof to the subject,
wherein the anti-CD47 antibody or the fragment thereof blocks an interaction between CD47 and SIRPα.

20. The method according to claim 19 , wherein the sub-therapeutic dose is administered at a dose from 0.05 mg/kg to 7.5 mg/kg.

21. The method according to claim 19 , wherein the sub-therapeutic dose is administered at a dose from 0.05 mg/kg to 5 mg/kg.

22. The method according to claim 19 , wherein the sub-therapeutic dose is administered at a dose from 0.1 mg/kg to 7.5 mg/kg.

23. The method according to claim 19 , wherein the sub-therapeutic dose is administered at a dose from 0.1 mg/kg to 5 mg/kg.

24. The method according to claim 19 , wherein the sub-therapeutic dose is administered at a dose from 1 mg/kg to 7.5 mg/kg.

25. The method according to claim 19 , wherein the sub-therapeutic dose is administered at a dose from 1 mg/kg to 5 mg/kg.

26. The method according to claim 19 , wherein the sub-therapeutic dose is administered at a dose of 1 mg/kg.

27. The method according to claim 19 , wherein the therapeutically effective dose is administered at a dose from 10 mg/kg to 40 mg/kg.

28. The method according to claim 19 , wherein the therapeutically effective dose is administered at a dose of 30 mg/kg.

29. The method according to claim 19 , wherein step (b) is performed in a range from 3 days to 21 days after beginning the administering of the sub-therapeutic dose.

30. The method according to claim 19 , wherein the sub-therapeutic dose increases the production of the reticulocytes.

31. The method according to claim 19 , wherein in step (a), the sub-therapeutic dose is determined to be effective by measuring in a blood sample from the human subject at least one of: an increase in an absolute or relative number of reticulocytes, an increase in a level of erythropoietin, and a decrease in a level of hemoglobin levels.

32. The method of claim 31 , wherein a reticulocyte count is at least 400×10 9 reticulocytes per liter (L).

33. The method of claim 19 , wherein step (b) comprises administering the anti-CD47 antibody or the fragment thereof in two or more doses of escalating concentration until a therapeutically effective dose is administered.

34. The method according to claim 19 , wherein step (b) comprises administering two or more therapeutically effective doses.

35. The method of claim 19 , wherein the anti-CD47 antibody is a monoclonal antibody.

36. The method of claim 19 , wherein the anti-CD47 antibody is a humanized antibody or a chimeric antibody.

Assignees

• Univ Leland Stanford Junior

Inventors

• Willingham Stephen
• Howard Maureen
• Liu Jie
• Majeti Ravindra
• Prohaska Susan Sweeney
• Volkmer Anne Kathrin
• Volkmer Jens-Peter
• Weissman Irving L

Classifications

• A61K2039/54

  characterised by the route of administration · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title