IP Library › Granted Patent US 12,258,403
Granted Patent B2
US 12,258,403 · App. 18/164,252 · Granted Mar 25, 2025

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

Inventors: Stephen Willingham (Sammamish, WA); Maureen Howard (Los Altos Hills, CA); Jie Liu (Palo Alto, CA); Ravindra Majeti (Palo Alto, CA); Susan Sweeney Prohaska (Mountain View, CA); Anne K. Volkmer (Duesseldorf, DE); Jens-Peter Volkmer (Menlo Park, CA); Irving L. Weissman (Stanford, CA)
Assignee: The Board of Trustees of the Leland Stanford Junior University
C07K16/2803A61K38/1774A61K39/3955C07K16/2896A61K38/1816A61K2039/505A61K2039/54A61K2039/545C07K2317/24C07K2317/33C07K2317/73C07K2317/76C07K2317/92C07K2319/30Y02A50/30
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Quick Facts
Patent No.
US 12,258,403
App. No.
18/164,252
Granted
Mar 25, 2025
Kind
B2
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.

Claims (22)

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.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 11, 2023
From: WILLINGHAM, STEPHEN; HOWARD, MAUREEN; LIU, JIE; MAJETI, RAVINDRA; PROHASKA, SUSAN; VOLKMER, ANNE K.; VOLKMER, JENS-PETER; WEISSMAN, IRVING L.
To: THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
Reel/Frame 063290/0454 →
Continuity (8)
Continuation 17734904 · May 2, 2022
Continuation 17401046 · Aug 12, 2021
Continuation 17102183 · Nov 23, 2020
Continuation 16375238 · Apr 4, 2019
Division 15423325 · Feb 2, 2017
Continuation 14769069
Provisional Application 61800102 · Mar 15, 2013
Related Publication 20230303688A1 · Sep 28, 2023
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