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. An antibody or antigen-binding fragment thereof that specifically binds human LAG3 of SEQ ID NO: 53 comprising:
(a) the CDR1, CDR2, and CDR3 of a V L region of an immunoglobulin chain that comprises the amino acid sequence set forth in SEQ ID NO: 2 or 4; and
(b) the CDR1, CDR2, and CDR3 of a V H region of an immunoglobulin chain that comprises the amino acid sequence set forth in SEQ ID NO: 1 or 3.
2. The antibody or fragment of claim 1 comprising:
a light chain variable domain comprising:
CDR-L1 that comprises the amino acid sequence in SEQ ID NO: 8;
CDR-L2 that comprises the amino acid sequence in SEQ ID NO: 9; and
CDR-L3 that comprises the amino acid sequence: in SEQ ID NO: 10; and
a heavy chain variable domain comprising:
CDR-H1 that comprises the amino acid sequence in SEQ ID NO: 5;
CDR-H2 that comprises the amino acid sequence in SEQ ID NO: 6; and
CDR-H3 that comprises the amino acid sequence in SEQ ID NO: 7.
3. The antibody or antigen-binding fragment of claim 1 comprising:
a light chain variable region comprising: CDR-L1 that comprises the amino acid sequence in SEQ ID NO: 14; CDR-L2 that comprises the amino acid sequence in SEQ ID NO: 15; and
CDR-L3 that comprises the amino acid sequence in SEQ ID NO: 16; and a heavy chain variable region comprising: CDR-H1 that comprises the amino acid sequence in SEQ ID NO: 11;
CDR-H2 that comprises the amino acid sequence in SEQ ID NO: 12; and CDR-H3 that comprises the amino acid sequence in SEQ ID NO: 13.
4. The antibody or antigen-binding fragment of claim 1 comprising:
(1)
a light chain immunoglobulin comprising CDR-L1, CDR-L2 and CDR-L3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 2, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 2; and
a heavy chain immunoglobulin comprising CDR-H1, CDR-H2 and CDR-H3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 1, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 1; or
(2)
a light chain immunoglobulin comprising CDR-L1, CDR-L2 and CDR-L3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 4, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 4; and a heavy chain immunoglobulin comprising CDR-H1, CDR-H2 and CDR-H3 of the immunoglobulin comprising the amino acid sequence of SEQ ID NO: 3, and having at least 90% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO: 3.
5. The antibody or antigen-binding fragment of claim 4 wherein said sequence identity is at least 95%, 96%, 97%, 98%, 99% or 100%.
6. The antibody or antigen-binding fragment of claim 5 comprising:
(1)
a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 2; and
a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 1; or
(2)
a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 4; and
a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 3; or
(3)
a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 22; and
a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 21; or
(4)
a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 24; and
a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 23.
7. The antibody or fragment of claim 6 which is glycosylated with engineered yeast N-linked glycans or CHO N-linked glycans.
8. The antibody or fragment of claim 6 which is an antibody.
9. The antibody or antigen-binding fragment of claim 5 comprising:
a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 4; and
a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 3.
10. The antibody of claim 5 comprising:
a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 24;
and a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 23.
11. A composition or kit comprising the antibody, or antigen-binding fragment, of claim 1 and, optionally, a pharmaceutically acceptable carrier or diluent; which is optionally in association with a further therapeutic agent.
12. The composition or kit of claim 11 wherein the further therapeutic agent is an anti-PD-1 antibody.
13. An antibody or antigen-binding fragment thereof that specifically binds human LAG3 of SEQ ID NO: 53 comprising a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 2, and a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 1, wherein X 1 =E, X 2 =G and X 3 =L; X 1 =Q, X 2 =M and X 3 =M; X 1 =E, X 2 =A and X 3 =L; or X 1 =E, X 2 =M and X 3 =L.
14. The antibody or antigen-binding fragment thereof of claim 13 comprising:
a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 2, and a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 1, wherein X 1 =E, X 2 =G and X 3 =L.
15. The antibody of claim 13 comprising: a light chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 22; and a heavy chain immunoglobulin comprising the amino acid sequence set forth in SEQ ID NO: 21; wherein X 1 =E, X 2 =G and X 3 =L.
16. The antibody of claim 13 comprising: a light chain immunoglobulin comprising an amino acid sequence set forth in SEQ ID NO: 22, and a heavy chain immunoglobulin comprising an amino acid sequence set forth in SEQ ID NO: 21, wherein X 1 =Q, X 2 =M and X 3 =M.
17. The antibody of claim 13 comprising: a light chain immunoglobulin comprising an amino acid sequence set forth in SEQ ID NO: 22, and a heavy chain immunoglobulin comprising an amino acid sequence set forth in SEQ ID NO:21, wherein X 1 =E, X 2 =A and X 3 =L.
18. The antibody of claim 13 comprising: a light chain immunoglobulin comprising an amino acid sequence set forth in SEQ ID NO: 22, and a heavy chain immunoglobulin comprising an amino acid sequence set forth in SEQ ID NO: 21, wherein X 1 =E, X 2 =M and X 3 =L.