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

Patent metadata

Field	Value
Publication number	US-9623079-B2
Application number	US-201414769069-A
Country	US
Kind code	B2
Filing date	Feb 26, 2014
Priority date	Mar 15, 2013
Publication date	Apr 18, 2017
Grant date	Apr 18, 2017

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 of treating a mammalian subject with cancer with a therapeutic dose of an anti-CD47 agent that blocks the interaction between CD47 and SIRPα, selected from: an antibody that binds to CD47; an antibody that binds to SIRPα; a soluble SIRPα-binding CD47 fragment; and a soluble CD47-binding SIRPα fragment or a combination thereof, for treatment of the cancer, the method comprising:
(a) administering a sub-therapeutic dose of one of the anti-CD47 agents to the subject, wherein the sub-therapeutic dose is effective to increase production of reticulocytes; and
(b) administering a therapeutically effective dose of at least one of the anti-CD47 agents to the subject, wherein step (b) is performed in a range from about 3 days to about 21 days after beginning step (a).

2. The method according to claim 1 , wherein step (b) is performed in a range from about 6 days to about 8 days after beginning step (a).

3. The method according to claim 1 , further comprising after step (a) and prior to step (b): a step of determining whether administration of the sub-therapeutic dose was effective by detecting in a blood sample from the subject one or more of: an increase in the absolute or relative number of reticulocytes; an increase in the level of EPO; or a decrease in hemoglobin levels.

4. The method according to claim 3 , wherein the determining step comprises performing a reticulocyte count, wherein administration of the sub-therapeutic dose is determined to have been effective if the reticulocyte count is about 400×10 9 reticulocytes per liter (L) or more.

5. The method according to claim 3 , wherein the determining step is performed in a range from about 3 days to about 12 days after beginning step (a).

6. The method according to claim 1 , further comprising after step (a) and prior to step (b):
administering a second sub-therapeutic dose of one of the anti-CD47 agents to the subject wherein step (b) is performed in a range from about 3 days to about 21 days after administering the second sub-therapeutic dose.

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

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

9. The method according to claim 1 , comprising administering in the therapeutic dose of (b) a combination of two or more anti-CD47 agents to the subject.

10. The method of claim 1 , wherein the mammalian subject is a human.

11. A method of treating a human subject with cancer with a therapeutic dose of an anti-CD47 antibody that blocks the interaction between CD47 and SIRPα for treatment of the cancer, the method comprising:
(a) administering a sub-therapeutic dose of the anti-CD47 antibody to the subject wherein the sub-therapeutic dose is sufficient to increase production of reticulocytes; and
(b) administering a therapeutically effective dose of the anti-CD47 antibody to the subject,
wherein step (b) is performed in a range from about 3 days to about 21 days after beginning step (a).

12. The method of claim 11 , wherein the sub-therapeutic dose is less than 10 mg/kg body weight.

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

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K38/1774

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