Therapeutic cd47 antibodies

Abstract

Provided are anti-CD47 monoclonal antibodies (anti-CD47 mAbs) with distinct functional profiles as described herein, methods to generate anti-CD47 mAbs, and to methods of using these anti-CD47 mAbs as therapeutics for the prevention and treatment of solid and hematological cancers, ischemia-reperfusion injury, cardiovascular diseases, autoimmune diseases, inflammatory diseases or as diagnostics for determining the level of CD47 in tissue samples.

What is claimed is: 
     
         1 . A monoclonal antibody, or an antigen binding fragment thereof, which:
 a. binds to human CD47;   b. blocks SIRPα binding to human CD47;   c. increases phagocytosis of human tumor cells;   d. induces death of human tumor cells; and
 wherein said monoclonal antibody, or an antigen binding fragment thereof, binds normal cells with an apparent K d  of at least 8-fold greater compared to binding to tumor cells. 
   
     
     
         2 . The monoclonal antibody, or antigen binding fragment thereof, of  claim 1 , wherein the normal cell is chosen from an endothelial cell, a skeletal muscle cell, an epithelial cell, a PBMC, a T cell, a red blood cell, a peripheral blood mononuclear cell, an aortic endothelial cell, a skeletal muscle cell, a microvascular endothelial cell, a renal tubular epithelial cell, a peripheral blood CD3+ cell, and a peripheral blood mononuclear cell. 
     
     
         3 . The monoclonal antibody, or antigen binding fragment thereof, of  claim 2 , wherein the monoclonal antibody, or antigen binding fragment thereof, further exhibits pH-dependent binding to human CD47 present on a cell. 
     
     
         4 . The monoclonal antibody, or antigen binding fragment thereof, of  claim 3 , wherein the pH-dependent binding to human CD47 has a greater affinity for human CD47 at an acidic pH compared to physiological pH.