Anti-LAG3 antibodies and antigen-binding fragments
The present invention includes antibodies and antigen-binding fragments thereof that specifically bind to human or cynomolgous monkey LAGS as well as immunoglobulin chains thereof and polynucleotides encoding the same along with injection devices comprising such antibodies or fragments. Vaccines including such antibodies and fragments as well as compositions comprising the antibodies and fragments (e.g., including anti-PD1 antibodies) are included in the invention. Methods for treating or preventing cancer or infection using such compositions are also provided. In addition, methods for recombinant expression of the antibodies and fragments are part of the present invention.
1. An antibody or antigen-binding fragment thereof that specifically binds human LAG3 comprising:
a light chain variable domain comprising:
CDR-L1 that comprises the amino acid sequence: KASQSLDYEGDSDMN (SEQ ID NO: 38);
CDR-L2 that comprises the amino acid sequence: GASNLES (SEQ ID NO: 39); and
CDR-L3 that comprises the amino acid sequence: QQSTEDPRT (SEQ ID NO: 40); and
a heavy chain variable domain comprising:
CDR-H1 that comprises the amino acid sequence: DYNVD (SEQ ID NO: 33);
CDR-H2 that comprises the amino acid sequence: DINPNDGGTIYAQKFQE (SEQ ID NO: 457); and
CDR-H3 that comprises the amino acid sequence: NYRWFGAMDH (SEQ ID NO: 35).
2. The antibody or antigen-binding fragment of claim 1 comprising one or more of CHO N-linked glycans selected from the group consisting of G0-F, G1-F, G2-F, G0, G1, G2 and Man5.
3. The antibody or antigen-binding fragment of claim 1 which is an antibody.
4. A composition comprising the antibody or antigen-binding fragment of claim 1 and a pharmaceutically acceptable carrier or diluent.
5. A vaccine comprising an antigen and a pharmaceutically acceptable carrier in association with an antibody or antigen-binding fragment of claim 1 .
6. A vessel or injection device comprising the antibody or antigen-binding fragment of claim 1 .
7. An antibody or antigen-binding fragment thereof that specifically binds human LAG3 comprising: a light chain variable domain comprising amino acids 21-131 of SEQ ID NO: 126 ; and a heavy chain variable domain comprising amino acids 1-119 of SEQ ID NO: 116.
8. An antibody comprising: a light chain comprising the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126 ; and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 116.
9. The antibody or antigen-binding fragment of claim 1 that is expressed from a Chinese hamster ovary cell.
10. The antibody or antigen-binding fragment of claim 7 that is expressed from a Chinese hamster ovary cell.
11. The antibody of claim 8 that is expressed from a Chinese hamster ovary cell.
12. An antibody that consists of two heavy chains and two light chains, wherein each light chain comprises the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126 and each heavy chain comprises the amino acid sequence set forth in amino acids 1-119 of SEQ ID NO: 116 and a human IgG4 constant domain.
13. An antibody that consists of two heavy chains and two light chains, wherein each light chain comprises the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126 and each heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 116.
14. An antibody that consists of two heavy chains and two light chains, wherein each light chain consists of the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126 and each heavy chain consists of the amino acid sequence set forth in SEQ ID NO: 116.
15. The antibody or antigen-binding fragment of claim 7 that is an antibody comprising a light chain comprising the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126 and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 110.
16. The antibody of claim 12 that is expressed from a Chinese hamster ovary cell.
17. The antibody of claim 13 that is expressed from a Chinese hamster ovary cell.
18. The antibody of claim 14 that is expressed from a Chinese hamster ovary cell.
19. The antibody of claim 15 that is expressed from a Chinese hamster ovary cell.
20. The antibody or antigen binding fragment of claim 1 that is humanized.
21. A composition comprising:
a) an antibody or antigen binding fragment comprising: a light chain variable domain comprising amino acids 21-131 of SEQ ID NO: 126 ; and a heavy chain variable domain comprising amino acids 1-119 of SEQ ID NO: 116; and
b) pembrolizumab.
22. A composition comprising:
a) an antibody comprising a light chain comprising the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126 and a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 116; and
b) pembrolizumab.
23. A composition comprising:
a) an antibody that consists of two heavy chains and two light chains, wherein each light chain comprises the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126 and each heavy chain comprises the amino acid sequence set forth in amino acids 1-119 of SEQ ID NO: 116 and a human IgG4 constant domain; and
b) pembrolizumab.
24. A composition comprising:
a) an antibody that consists of two heavy chains and two light chains, wherein each light chain comprises the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126 and each heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 116; and
b) pembrolizumab.
25. A composition comprising:
a) an antibody that consists of two heavy chains and two light chains, wherein each light chain consists of the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126 and each heavy chain consists of the amino acid sequence set forth in SEQ ID NO: 116; and
b) pembrolizumab.
26. A kit comprising the antibody or antigen-binding fragment of claim 7 and pembrolizumab.
27. A kit comprising the antibody of claim 8 and pembrolizumab.
28. A kit comprising the antibody of claim 12 and pembrolizumab.
29. A kit comprising the antibody of claim 13 and pembrolizumab.
30. A kit comprising the antibody of claim 14 and pembrolizumab.
31. An antibody that consists of two heavy chains and two light chains, wherein each light chain consists of the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126 and each heavy chain consists of the amino acid sequence set forth in amino acids 1-119 of SEQ ID NO: 116 and a human IgG4 constant region with a S228P mutation according to the EU system.
32. An antibody that consists of two heavy chains and two light chains, wherein each light chain consists of the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126 and each heavy chain consists of the amino acid sequence set forth in amino acids 1-119 of SEQ ID NO: 116 and a human IgG4 constant region.
33. An antibody that consists of two heavy chains and two light chains, wherein each light chain consists of the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126 and each heavy chain comprises the amino acid sequence set forth in amino acids 1-119 of SEQ ID NO: 116.
34. The antibody of claim 31 that is expressed from a Chinese hamster ovary cell.
35. The antibody of claim 32 that is expressed from a Chinese hamster ovary cell.
36. The antibody of claim 33 that is expressed from a Chinese hamster ovary cell.
37. A kit comprising the antibody of claim 31 and pembrolizumab.
38. A kit comprising the antibody of claim 32 and pembrolizumab.
39. A kit comprising the antibody of claim 33 and pembrolizumab.
40. A composition comprising:
a) an antibody that consists of two heavy chains and two light chains, wherein each light chain consists of the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126 and each heavy chain comprises the amino acid sequence set forth in amino acids 1-119 of SEQ ID NO: 116; and
b) pembrolizumab.
41. A composition comprising:
a) an antibody that consists of two heavy chains and two light chains, wherein each light chain consists of the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126 and each heavy chain consists of the amino acid sequence set forth in amino acids 1-119 of SEQ ID NO: 116 and a human IgG4 constant region with a S228P mutation according to the EU system; and
b) pembrolizumab.