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

Patent metadata

Field	Value
Publication number	US-12258403-B2
Application number	US-202318164252-A
Country	US
Kind code	B2
Filing date	Feb 3, 2023
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 myeloma 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, wherein the myeloma is treated.

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 step (a).

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, or a decrease in a level of hemoglobin levels.

14. The method of claim 13 , wherein following step (a) the number of a reticulocytes 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 of the anti-CD47 antibody or the fragment thereof.

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. The method of claim 18 , 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 a containing the VL complementary regions, CDR1, CDR2 and CDR3, respectively set forth in SEQ ID NO:9, 10 and 11.

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

• 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