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 method of producing a polypeptide comprising 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 thereof that specifically binds to human Lymphocyte Activation Gene-3 (LAG3) comprising:
a. culturing a host cell comprising a polynucleotide encoding the light chain variable domain, the heavy chain variable domain, or both the light chain variable domain and the heavy chain variable domain, of the antibody or antigen-binding fragment in a culture medium under conditions wherein the polypeptide is expressed; 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: DINPNDGGTIYAQKFQE (SEQ ID NO: 457); and
CDR-H3 that comprises the amino acid sequence: NYRWFGAMDH (SEQ ID NO: 35); and
b. recovering the polypeptide from the host cell or culture medium.
2. The method of claim 1 , wherein the antibody or antigen-binding fragment is humanized.
3. A method of producing an antibody or antigen-binding fragment thereof that specifically binds to human Lymphocyte Activation Gene-3 (LAG3) comprising:
a. culturing a host cell comprising a polynucleotide encoding a light chain variable domain and a polynucleotide encoding a heavy chain variable domain, or a polynucleotide encoding a light chain variable domain and a heavy chain variable domain, of the antibody or antigen-binding fragment in a culture medium under conditions wherein the antibody or antigen-binding fragment thereof is expressed; 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; and
b. recovering the antibody or antigen-binding fragment from the host cell or culture medium.
4. The method of claim 3 , wherein the host cell comprises a polynucleotide encoding a light chain and a polynucleotide encoding a heavy chain, or a polynucleotide encoding 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.
5. A method of producing an antibody that specifically binds to human Lymphocyte Activation Gene-3 (LAG3) comprising:
a. culturing a host cell comprising a polynucleotide encoding a light chain and a polynucleotide encoding a heavy chain, or a polynucleotide encoding a light chain and a heavy chain, of the antibody in a culture medium under conditions wherein the antibody is expressed; 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; and
b. recovering the antibody from the host cell or culture medium.
6. The method of claim 1 , wherein the host cell is a Chinese hamster ovary cell.
7. The method of claim 2 , wherein the host cell is a Chinese hamster ovary cell.
8. The method of claim 3 , wherein the host cell is a Chinese hamster ovary cell.
9. The method of claim 4 , wherein the host cell is a Chinese hamster ovary cell.
10. The method of claim 5 , wherein the host cell is a Chinese hamster ovary cell.
11. A method of producing an antibody or antigen-binding fragment thereof that specifically binds to human Lymphocyte Activation Gene-3 (LAG3) comprising:
a. culturing a host cell comprising a polynucleotide encoding a light chain variable domain and a polynucleotide encoding a heavy chain variable domain, or a polynucleotide encoding a light chain variable domain and a heavy chain variable domain, of the antibody or antigen-binding fragment in a culture medium under conditions wherein the antibody or antigen-binding fragment thereof is expressed;
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
wherein 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: DINPNDGGTIYAQKFQE (SEQ ID NO: 457); and
CDR-H3 that comprises the amino acid sequence: NYRWFGAMDH (SEQ ID NO: 35); and
b. recovering the antibody or antigen-binding fragment from the host cell or culture medium.
12. The method of claim 11 , wherein the host cell is a Chinese hamster ovary cell.