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

Patent metadata

Field	Value
Publication number	US-11518806-B2
Application number	US-202217734949-A
Country	US
Kind code	B2
Filing date	May 2, 2022
Priority date	Mar 15, 2013
Publication date	Dec 6, 2022
Grant date	Dec 6, 2022

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

18. The method according to claim 17 , wherein the sub-therapeutic dose is administered at a dose from 0.05 mg/kg to 7.5 mg/kg.

19. The method according to claim 17 , wherein the sub-therapeutic dose is administered at a dose from 0.05 mg/kg to 5 mg/kg.

20. The method according to claim 17 , wherein the sub-therapeutic dose is administered at a dose from 0.1 mg/kg to 7.5 mg/kg.

21. The method according to claim 17 , wherein the sub-therapeutic dose is administered at a dose from 0.1 mg/kg to 5 mg/kg.

22. The method according to claim 17 , wherein the sub-therapeutic dose is administered at a dose from 1 mg/kg to 7.5 mg/kg.

23. The method according to claim 17 , wherein the sub-therapeutic dose is administered at a dose from 1 mg/kg to 5 mg/kg.

24. The method according to claim 17 , wherein the sub-therapeutic dose is administered at a dose of 1 mg/kg.

25. The method according to claim 17 , wherein the therapeutically effective dose is administered at a dose from 10 mg/kg to 40 mg/kg.

26. The method according to claim 17 , wherein the therapeutically effective dose is administered at a dose of 30 mg/kg.

27. The method according to claim 17 , wherein step (b) is performed in a range from 3 days to 21 days after beginning the administering of the sub-therapeutic dose.

28. The method according to claim 17 , wherein the sub-therapeutic dose increases the production of the reticulocytes.

29. The method according to claim 17 , 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.

30. The method of claim 28 , wherein a reticulocyte count is at least 400×10 9 reticulocytes per liter (L).

31. The method of claim 17 , wherein step (b) comprises administering the soluble CD47-binding SIRPα fragment in two or more doses of escalating concentration until a therapeutically effective dose is administered.

32. The method according to claim 17 , wherein step (b) comprises administering two or more therapeutically effective doses.

33. The method according to claim 17 , wherein the hematological cancer is leukemia.

34. The method of claim 31 , wherein the leukemia is acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL).

Assignees

• Univ Leland Stanford Junior

Inventors

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

Classifications

• C07K2319/30

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

• C07K16/2803 Primary

  against the immunoglobulin superfamily · CPC title

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title