Antigen binding proteins
This application discloses antigen binding proteins that bind Lymphocyte Activation Gene 3 (LAG-3), and more particularly to antigen binding proteins that cause depletion of LAG-3+ activated T cells.
1. An antigen binding protein which is capable of binding Lymphocyte Activation Gene 3 (LAG-3) and which comprises
CDRL1 comprising SEQ ID NO:1;
CDRL2 comprising SEQ ID NO:2;
CDRL3 comprising SEQ ID NO:3;
CDRH1 comprising SEQ ID NO:6;
CDRH2 comprising SEQ ID NO:7; and
CDRH3 comprising SEQ ID NO:8.
2. An antigen binding protein according to claim 1 , which comprises a) the variable light chain (VL) comprising SEQ ID NO:4 and b) the variable heavy chain (VH) comprising SEQ ID NO:9.
3. An antigen binding protein according to claim 1 , which is capable of binding recombinant human sLAG-3 of SEQ ID NO:51 with a KD of less than 1 nM when determined by surface Plasmon resonance analysis.
4. An antigen binding protein according to claim 1 , wherein the antigen binding protein comprises a human IgG1 constant region and is capable of depleting LAG-3+ activated human T cells.
5. An antigen binding protein according to claim 4 , wherein the antigen binding protein comprises a human IgG1 constant region and is capable of causing greater than 40% depletion of antigen specific CD4 LAG-3 + human T cells by ADCC in an in-vitro assay using primary human T cells.
6. An antigen binding protein according to claim 1 , wherein the antigen binding protein is a humanised antibody.
7. An antigen binding protein according to claim 6 , wherein the humanised antibody comprises an IgG1 constant region.
8. An antigen binding protein according to claim 7 , wherein the humanised antibody comprises a) a light chain sequence with at least 97% identity to SEQ ID NO:5, and b) a heavy chain sequence with at least 97% identity to SEQ ID NO:10.
9. An antigen binding protein according to claim 8 , wherein the humanised antibody comprises a) a light chain sequence comprising SEQ ID NO:5, and b) a heavy chain sequence comprising SEQ ID NO:10.
10. An antigen binding protein according to claim 7 , wherein the humanised antibody is non-fucosylated.
11. An antigen binding protein produced by a host cell that comprises an expression vector that comprises a nucleic acid molecule which encodes an antigen binding protein of claim 1 .
12. A pharmaceutical composition comprising a) an antigen binding protein according to claim 1 , and b) a pharmaceutically acceptable carrier.
13. An antigen binding protein according to claim 4 , wherein the antigen binding protein comprises a human IgG1 constant region and is capable of causing greater than 40% depletion of antigen specific CD8 LAG-3 + human T cells by ADCC in an in-vitro assay using primary human T cells.
14. An antigen binding protein produced by a host cell that comprises an expression vector that comprises a nucleic acid molecule which encodes an antigen binding protein of claim 7 .
15. A pharmaceutical composition comprising a) an antigen binding protein according to claim 7 , and b) a pharmaceutically acceptable carrier.
16. An antigen binding protein according to claim 8 , wherein the humanised antibody is non-fucosylated.
17. An antigen binding protein according to claim 9 , wherein the humanised antibody is non-fucosylated.
18. An antigen binding protein according to claim 1 , wherein the antigen binding protein is capable of binding LAG-3 expressed on activated human CD3+ T cells.