Methods and compositions for inhibiting cd32b expressing cells

Abstract

The present invention relates to immunoglobulins that bind FcγRIIb+ cells and coengage the antigen on the cell's surface and an FcγRIIb on the cell's surface, methods for their generation, and methods for using the immunoglobulins.

1 - 20 . (canceled) 
     
     
         21 . An immunoglobulin having affinity for an antigen on a B cell or dendritic cell:
 wherein the immunoglobulin has an enhanced binding affinity to FcγRIIb and a reduced binding affinity to FcγRIIIa relative to the parent Fc polypeptide,   said immunoglobulin coengages a target antigen selected from CD22, CD40, and CD72 on the cell surface and the FcγRIIb on the cell surface.   
     
     
         22 . The immunoglobulin according to  claim 21 , wherein said immunoglobulin has a Kd for FcγRIIb less than 100 nM. 
     
     
         23 . The immunoglobulin of  claim 21 , wherein said immunoglobulin comprises at least one amino acid modification at a position selected from the group consisting of 234, 235, 236, 237, 239, 265, 266, 267, 268, 298, 325, 326, 327, 328, 329, 330, 331, and 332, wherein numbering is according to the EU index, as in Kabat. 
     
     
         24 . The immunoglobulin of  claim 23 , wherein the cell is a B cell. 
     
     
         25 . The immunoglobulin of  claim 23 , wherein the target antigen is CD40. 
     
     
         26 . The immunoglobulin according to  claim 25 , wherein the amino acid modification is at position 267. 
     
     
         27 . The immunoglobulin according to  claim 26 , wherein the amino acid modification is a substitution, S267E. 
     
     
         28 . The immunoglobulin according to  claim 25 , wherein the amino acid modification is at position 328. 
     
     
         29 . The immunoglobulin according to  claim 28 , wherein the amino acid modification is a substitution, L328F. 
     
     
         30 . The immunoglobulin according to  claim 25 , wherein the amino acid modifications are at positions 267 and 328. 
     
     
         31 . The immunoglobulin according to  claim 30 , wherein the amino acid modifications are substitutions S267E and L328F. 
     
     
         32 . A pharmaceutical composition comprising the immunoglobulin according to  claim 25 , and a pharmaceutically acceptable carrier. 
     
     
         33 . The immunoglobulin of  claim 21 , wherein said immunoglobulin comprises at least one amino acid modification at a position selected from the group consisting of 234, 235, 236, 237, 239, 265, 266, 267, 268, 298, 325, 326, 327, 328, 329, 330, 331, and 332 as compared to a parent Fc region, wherein numbering is according to the EU index, as in Kabat. 
     
     
         34 . The immunoglobulin according to  claim 33 , wherein said amino acid modification is at least one substitution selected from the group consisting of L234W, L235I, L235Y, L235R, L235D, G236D, G236N, S267D, S267E, L328F, and L328Y. 
     
     
         35 . The immunoglobulin according to  claim 33 , wherein said amino acid modification is at least one substitution selected from the group consisting of L234W, L235I, L235Y, L235R, G236D, S267D, S267E, and L328F, wherein numbering is according to the EU index, as in Kabat.