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 LAG3 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. A polynucleotide encoding a light chain variable domain, a heavy chain variable domain, or both a light chain variable domain and a heavy chain variable domain of an antibody or antigen binding fragment that specifically binds to human Lymphocyte Activation Gene-3 (LAG3), wherein the light chain variable domain comprises:
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
the heavy chain variable domain comprises:
CDR-H1 that comprises the amino acid sequence: DYNVD (SEQ ID NO: 33);
CDR-H2 that comprises the amino acid sequence: DINPNX 1 GGTIYX 2 QKFX 3 X 4 (SEQ ID NO: 446), wherein,
X 1 =D, N, S or Q
X 2 =A or S
X 3 =Q or K, and
X 4 =E or G; and
CDR-H3 that comprises the amino acid sequence: NYRWFGAMDH (SEQ ID NO: 35).
2. The polynucleotide of claim 1 , wherein the antibody or antigen-binding fragment comprises:
(1)
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: DINPNNGGTIYAQKFQE (SEQ ID NO: 458); and
CDR-H3 that comprises the amino acid sequence: NYRWFGAMDH (SEQ ID NO: 35); or
(2)
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: DINPNSGGTIYAQKFQE (SEQ ID NO: 456); and
CDR-H3 that comprises the amino acid sequence: NYRWFGAMDH (SEQ ID NO: 35); or
(3)
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); or
(4)
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: DINPNQGGTIYAQKFQE (SEQ ID NO: 455); and
CDR-H3 that comprises the amino acid sequence: NYRWFGAMDH (SEQ ID NO: 35); or
(5)
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: DINPNGGGTIYAQKFQE (SEQ ID NO: 454); and
CDR-H3 that comprises the amino acid sequence: NYRWFGAMDH (SEQ ID NO: 35).
3. The polynucleotide of claim 1 , wherein the antibody or antigen-binding fragment comprises:
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: DINPNQGGTIYAQKFQE (SEQ ID NO: 457); and
CDR-H3 that comprises the amino acid sequence: NYRWFGAMDH (SEQ ID NO: 35).
4. The polynucleotide of claim 1 , wherein the antibody or antigen-binding fragment comprises:
(1)
a light chain variable domain comprising the amino acid sequence set forth in amino acids 21-131 of SEQ ID NO: 126, and
a heavy chain variable domain comprising the amino acid sequence set forth in amino acids 1-119 of SEQ ID NO: 106; or
(2)
a light chain variable domain comprising the amino acid sequence set forth in amino acids 21-131 of SEQ ID NO: 126, and
a heavy chain variable domain comprising the amino acid sequence set forth in amino acids 1-119 of SEQ ID NO: 108; or
(3)
a light chain variable domain comprising the amino acid sequence set forth in amino acids 21-131 of SEQ ID NO: 126, and
a heavy chain variable domain comprising the amino acid sequence set forth in amino acids 1-119 of SEQ ID NO: 110; or
(4)
a light chain variable domain comprising the amino acid sequence set forth in amino acids 21-131 of SEQ ID NO: 126, and
a heavy chain variable domain comprising the amino acid sequence set forth in amino acids 1-119 of SEQ ID NO: 112; or
(5)
a light chain variable domain comprising the amino acid sequence set forth in amino acids 21-131 of SEQ ID NO: 126, and
a heavy chain variable domain comprising the amino acid sequence set forth in amino acids 1-119 of SEQ ID NO: 122.
5. The polynucleotide of claim 1 encoding a light chain, a heavy chain, or both a light chain and a heavy chain of an antibody that comprises:
(1)
a light chain immunoglobulin comprising the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126, and
a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 106; or
(2)
a light chain immunoglobulin comprising the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126, and
a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 108; or
(3)
a light chain immunoglobulin comprising the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126, and
a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 110; or
(4)
a light chain immunoglobulin comprising the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126, and
a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 112; or
(5)
a light chain immunoglobulin comprising the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126, and
a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 114; or
(6)
a light chain immunoglobulin comprising the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126, and
a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 116; or
(7)
a light chain immunoglobulin comprising the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126, and
a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 118; or
(8)
a light chain immunoglobulin comprising the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126, and
a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 120; or
(9)
a light chain immunoglobulin comprising the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126, and
a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 122.
6. The polynucleotide of claim 1 , wherein the antibody or antigen-binding fragment is humanized.
7. The polynucleotide of claim 2 , wherein the antibody or antigen-binding fragment is humanized.
8. The polynucleotide of claim 3 , wherein the antibody or antigen-binding fragment is humanized.
9. A polynucleotide encoding a light chain variable domain, a heavy chain variable domain, or both a light chain variable domain and a heavy chain variable domain of an antibody or antigen binding fragment that specifically binds to human Lymphocyte Activation Gene-3 (LAG3), wherein the light chain variable domain comprises amino acids 21-131 of SEQ ID NO: 126 and the heavy chain variable domain comprises amino acids 1-119 of SEQ ID NO: 116.
10. The polynucleotide of claim 9 encoding a light chain, a heavy chain, or both a light chain and a heavy chain of the antibody, wherein the light chain comprises the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126 and the heavy chain comprises the amino acid sequence set forth in amino acids 1-119 of SEQ ID NO: 116.
11. A polynucleotide encoding a light chain, a heavy chain, or both a light chain and a heavy chain of an antibody that specifically binds to human Lymphocyte Activation Gene-3 (LAG3), wherein the light chain comprises the amino acid sequence set forth in amino acids 21-238 of SEQ ID NO: 126 and the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 116.
12. An expression vector comprising the polynucleotide of claim 1 .
13. An expression vector comprising the polynucleotide of claim 2 .
14. An expression vector comprising the polynucleotide of claim 9 .
15. An expression vector comprising the polynucleotide of claim 10 .
16. An expression vector comprising the polynucleotide of claim 11 .
17. A host cell comprising the expression vector of claim 12 .
18. A host cell comprising the expression vector of claim 13 .
19. A host cell comprising the expression vector of claim 14 .
20. A host cell comprising the expression vector of claim 15 .
21. A host cell comprising the expression vector of claim 16 .