US 12,233,093 B2
Engraftment of stem cells with a combination of an agent that targets stem cells and modulation of immunoregulatory signaling
Judith A. Shizuru, Palo Alto, CA (US); Irving L. Weissman, Stanford, CA (US); Kipp Andrew Weiskopf, Sudbury, MA (US); Aaron Michael Ring, New Haven, CT (US); Akanksha Chhabra, San Francisco, CA (US); and Peter Schnorr, Sudbury, MA (US)
Assigned to The Board of Trustees of the Leland Stanford Junior University, Stanford, CA (US)
Filed by The Board of Trustees of the Leland Stanford Junior University, Stanford, CA (US)
Filed on Jul. 18, 2022, as Appl. No. 17/867,321.
Application 17/867,321 is a continuation of application No. 16/526,794, filed on Jul. 30, 2019, granted, now 11,419,897.
Application 16/526,794 is a continuation of application No. 15/504,264, granted, now 10,406,179, issued on Sep. 10, 2019, previously published as PCT/US2015/046976, filed on Aug. 26, 2015.
Claims priority of provisional application 62/041,989, filed on Aug. 26, 2014.
Prior Publication US 2022/0347224 A1, Nov. 3, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 35/28 (2015.01); A61K 38/17 (2006.01); A61K 39/00 (2006.01); A61K 39/395 (2006.01); A61K 45/06 (2006.01); C07K 16/28 (2006.01)
CPC A61K 35/28 (2013.01) [A61K 38/1709 (2013.01); A61K 38/1774 (2013.01); A61K 38/1793 (2013.01); A61K 39/3955 (2013.01); A61K 45/06 (2013.01); C07K 16/2803 (2013.01); C07K 16/2878 (2013.01); C07K 16/2896 (2013.01); A61K 2039/505 (2013.01); A61K 2039/507 (2013.01); C07K 2317/74 (2013.01); C07K 2317/75 (2013.01); C07K 2317/76 (2013.01)] 17 Claims
 
1. A method of hematopoietic stem cell engraftment in a mammal, the method comprising:
contacting said mammal concomitantly with (i) a monoclonal antibody specific for CD117 at a dose of from 50 μg/kg body weight to 50 mg/kg body weight; and (ii) an agent that blocks interaction between CD47 and SIRPα, wherein the agent is selected from an anti-CD47 antibody, an anti-SIRPα antibody, a soluble SIRPα polypeptide or a fusion protein comprising a SIRPα polypeptide at a dose of from 50 μg/kg body weight to 100 mg/kg body weight; wherein the combination of doses is effective in ablating hematopoietic stem cells from bone marrow of said mammal; and
introducing exogenous hematopoietic stem cells to said mammal, wherein the exogenous hematopoietic stem cells engraft to provide for long-term multilineage hematopoietic engraftment.