Anti-sirp alpha antibodies

Abstract

The present invention relates to anti-SIRPα antibodies, as well as use of these antibodies in the treatment of diseases such as cancer and infectious disease.

1 . An isolated therapeutic antibody, comprising:
 a variable region that binds to human SIRPαV1 protein having the sequence of SEQ ID NO: 34 with an EC 50  of 10 nM or less,   wherein the variable region discriminates between human SIRP isoforms comprising a proline in the SIRP IgV domain at a position corresponding to Pro 74  of SEQ ID NO: 34 and human SIRP isoforms in which the proline corresponding to residue 74 of SEQ ID NO: 34 is replaced by alanine.   
     
     
         2 . An isolated therapeutic antibody according to  claim 1 , wherein the antibody inhibits binding of human SIRPα having the sequence of SEQ ID NO: 34 to human CD47 with an IC 50  of of 10 nM or less. 
     
     
         3 . An isolated therapeutic antibody according to  claim 1 , wherein the antibody binds to a cell expressing human SIRPαV2 protein with an EC 50  of 10 nM or less. 
     
     
         4 . An isolated therapeutic antibody according to  claim 3 , wherein the antibody binds to a cell expressing human SIRPαV1 protein having the sequence of SEQ ID NO: 34 with an EC 50  of 1 nM or less, and binds to a cell expressing human SIRPαV2 protein with an EC 50  of 1 nM or less. 
     
     
         5 . An isolated therapeutic antibody of  claim 1 , wherein the antibody is an IgG. 
     
     
         6 . An isolated therapeutic antibody of  claim 5 , wherein each of the two variable regions of the IgG binds to human SIRPαV1 protein having the sequence of SEQ ID NO: 34 with an EC 50  of 10 nM or less and discriminates between human SIRP isoforms comprising a proline in the SIRP IgV domain at a position corresponding to Pro 74  of SEQ ID NO: 34 and human SIRP isoforms in which the proline corresponding to residue 74 of SEQ ID NO: 34 is replaced by alanine. 
     
     
         7 . An isolated therapeutic antibody of  claim 5 , wherein the antibody exhibits a T20 “humanness” score of at least 79. 
     
     
         8 . An isolated therapeutic antibody of  claim 6 , wherein the antibody exhibits a T20 “humanness” score of at least 79. 
     
     
         9 . An isolated therapeutic antibody of  claim 4 , wherein the antibody is an IgG. 
     
     
         10 . An isolated therapeutic antibody of  claim 9 , wherein each of the two variable regions of the IgG binds to human SIRPαV1 protein having the sequence of SEQ ID NO: 34 with an EC 50  of 10 nM or less and discriminates between human SIRP isoforms comprising a proline in the SIRP IgV domain at a position corresponding to Pro 7 4 of SEQ ID NO: 34 and human SIRP isoforms in which the proline corresponding to residue 74 of SEQ ID NO: 34 is replaced by alanine. 
     
     
         11 . An isolated therapeutic antibody of  claim 9 , wherein the antibody exhibits a T20 “humanness” score of at least 79. 
     
     
         12 . An isolated therapeutic antibody of  claim 10 , wherein the antibody exhibits a T20 “humanness” score of at least 79. 
     
     
         13 . A composition comprising:
 the therapeutic antibody of  claim 1  and a pharmaceutically acceptable carrier or diluent.   
     
     
         14 . A composition comprising:
 the therapeutic antibody of  claim 4  and a pharmaceutically acceptable carrier or diluent.   
     
     
         15 . A composition comprising:
 the therapeutic antibody of  claim 5  and a pharmaceutically acceptable carrier or diluent.   
     
     
         16 . A composition comprising:
 the therapeutic antibody of  claim 6  and a pharmaceutically acceptable carrier or diluent.   
     
     
         17 . A composition comprising:
 the therapeutic antibody of  claim 7  and a pharmaceutically acceptable carrier or diluent.   
     
     
         18 . A composition comprising:
 the therapeutic antibody of  claim 8  and a pharmaceutically acceptable carrier or diluent.   
     
     
         19 . A composition comprising:
 the therapeutic antibody of  claim 9  and a pharmaceutically acceptable carrier or diluent.   
     
     
         20 . A composition comprising:
 the therapeutic antibody of  claim 10  and a pharmaceutically acceptable carrier or diluent.   
     
     
         21 . A composition comprising:
 the therapeutic antibody of  claim 11  and a pharmaceutically acceptable carrier or diluent.   
     
     
         22 . A composition comprising:
 the therapeutic antibody of  claim 12  and a pharmaceutically acceptable carrier or diluent.