Methods for achieving therapeutically effective doses of anti-CD47 agents

Patent metadata

Field	Value
Publication number	US-12258399-B2
Application number	US-202117401046-A
Country	US
Kind code	B2
Filing date	Aug 12, 2021
Priority date	Mar 15, 2013
Publication date	Mar 25, 2025
Grant date	Mar 25, 2025

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 cancer in a human subject, the method comprising:
(a) administering a sub-therapeutic dose of from 0.1 mg/kg to 10 mg/kg of an anti-CD47 antibody that blocks the interaction between CD47 and SIRPα, wherein the sub-therapeutic dose is sufficient to increase production of reticulocytes; and
(b) administering a therapeutically effective dose of an anti-CD47 antibody that blocks the interaction between CD47 and SIRPα; wherein step (b) is performed in a range of from 5 to 9 days after beginning step (a), thereby treating the cancer.

2. The method of claim 1 , wherein the sub-therapeutic dose is from 1 mg/kg to 5 mg/kg.

3. The method of claim 1 , wherein the sub-therapeutic dose is from 1 mg/kg to 3 mg/kg.

4. The method of claim 1 , wherein for step (b) a series of therapeutically effective doses is administered.

5. The method of claim 4 , wherein the series of therapeutically effective doses is administered at a dose from 10 mg/kg to 40 mg/kg.

6. The method of claim 1 , wherein the anti-CD47 antibody comprises a variable heavy (VH) region containing the VH complementarity regions, CDR1, CDR2 and CDR3, respectively set forth in SEQ ID NO:6, 7 and 8; and a variable light (VL) region containing the VL complementary regions, CDR1, CDR2 and CDR3, respectively set forth in SEQ ID NO:9, 10 and 11.

7. A method for treating cancer in a human subject, the method comprising:
(a) administering a sub-therapeutic dose of 1 mg/kg of an anti-CD47 antibody that blocks the interaction between CD47 and SIRPα, wherein the sub-therapeutic dose is sufficient to increase production of reticulocytes; and
(b) administering a series of therapeutically effective doses of an anti-CD47 antibody that blocks the interaction between CD47 and SIRPα of escalating concentration at doses from 10 mg/kg to about 30 mg/kg; wherein step (b) is administered semi-weekly, starting 8 days after beginning step (a); and wherein the anti-CD47 antibody comprises a variable heavy (VH) region containing the VH complementarity regions, CDR1, CDR2 and CDR3, respectively set forth in SEQ ID NO:6, 7 and 8; and a variable light (VL) region containing the VL complementary regions, CDR1, CDR2 and CDR3, respectively set forth in SEQ ID NO:9, 10 and 11, thereby treating the cancer.

8. The method of claim 7 , wherein the cancer is a pre-malignant condition.

9. The method of claim 7 , wherein the cancer is a hematologic cancer.

10. The method of claim 9 , wherein the hematologic cancer is a leukemia.

11. The method of claim 10 , wherein the leukemia is acute myeloid leukemia (AML).

12. The method of claim 9 , wherein the hematologic cancer is a lymphoma.

13. A method for treating cancer in a human subject, the method comprising:
(a) administering a series of two sub-therapeutic dose of 1 mg/kg of an anti-CD47 antibody that blocks the interaction between CD47 and SIRPα, wherein the sub-therapeutic dose is sufficient to increase production of reticulocytes; and
(b) administering a series of therapeutically effective doses of an anti-CD47 antibody that blocks the interaction between CD47 and SIRPα of escalating concentration at doses from 10 mg/kg to about 30 mg/kg; wherein step (b) is administered semi-weekly, starting 8 days after beginning step (a); and wherein the anti-CD47 antibody comprises a variable heavy (VH) region containing the VH complementarity regions, CDR1, CDR2 and CDR3, respectively set forth in SEQ ID NO:6, 7 and 8; and a variable light (VL) region containing the VL complementary regions, CDR1, CDR2 and CDR3, respectively set forth in SEQ ID NO:9, 10 and 11.

14. The method of claim 13 , wherein the cancer is a pre-malignant condition.

15. The method of claim 13 , wherein the cancer is a hematologic cancer.

16. The method of claim 15 , wherein the hematologic cancer is a leukemia.

17. The method of claim 16 , wherein the leukemia is acute myeloid leukemia (AML).

18. The method of claim 13 , wherein the hematologic cancer is a lymphoma.

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

• A61K38/1774

  Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules) · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• A61K38/1816

  Erythropoietin [EPO] · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• C07K2317/92

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