Methods and compositions for inhibiting CD32B expressing cells
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. An anti-CD19 immunoglobulin comprising:
a light chain; and
a heavy chain comprising an amino acid sequence of SEQ ID NO: 2 and amino acid substitution(s) in the Fc region selected from L234W, L235I, L235Y, L235R, L235D, G236D, G236N, S267D, S267E, L328F, and L328Y as compared to SEQ ID NO: 4, wherein the numbering is according to the EU index, as in Kabat.
2. The immunoglobulin of claim 1 , wherein the immunoglobulin comprises:
a light chain comprising an amino acid sequence of SEQ ID NO: 7.
3. The immunoglobulin of claim 1 , wherein the amino acid substitution(s) in the Fc region are selected from L234W, L235I, L235Y, L235R, G236D, S267D, S267E, and L328F.
4. The immunoglobulin according to claim 1 , wherein the amino acid substitution in the Fc region is S267E.
5. The immunoglobulin according to claim 1 , wherein the amino acid substitution in the Fc region is L328F.
6. The immunoglobulin according to claim 1 , wherein the amino acid substitution in the Fc region is S267E/L328F.
7. A pharmaceutical composition comprising the immunoglobulin according to claim 1 , and a pharmaceutically acceptable carrier.
8. The immunoglobulin of claim 2 , wherein the amino acid substitution(s) in the Fc region are selected from L234W, L235I, L235Y, L235R, G236D, S267D, S267E, and L328F.
9. The immunoglobulin according to claim 2 , wherein the amino acid substitution in the Fc region is S267E.
10. The immunoglobulin according to claim 2 , wherein the amino acid substitution in the Fc region is L328F.
11. The immunoglobulin according to claim 2 , wherein the amino acid substitution in the Fc region is S267E/L328F.
12. A pharmaceutical composition comprising the immunoglobulin according to claim 2 , and a pharmaceutically acceptable carrier.
13. The immunoglobulin of claim 1 , wherein the amino acid substitution(s) in the Fc region are selected from L235D/S267E, L235Y/S267E, L235D/S267D, L235I/S267E, L235I/S267D, L235Y/S267D, G236D/S267E, G236D/S267D, S267E/L328F, S267D/L328F, H268D/S267E, H268D/S267D, H268E/S267E, H268E/S267D, and G236N/S267E/L328F.
14. The immunoglobulin of claim 3 , wherein the amino acid substitution(s) in the Fc region are selected from L235D/S267E, L235Y/S267E, L235Y/S267D, G236D/S267E, S267E/L328F, H268D/S267E, H268E/S267E, H268E/S267D, and G236D/S267E/L328F.
15. The immunoglobulin of claim 8 , wherein the amino acid substitution(s) in the Fc region are selected from L235D/S267E, L235Y/S267E, L235Y/S267D, G236D/S267E, S267E/L328F, H268D/S267E, H268E/S267E, H268E/S267D, and G236D/S267E/L328F.
16. The immunoglobulin of claim 1 , wherein the amino acid substitution in the Fc region is S 267 D.