Antibodies to human programmed death receptor PD-1
Antibodies which block binding of hPD-1 to hPD-L1 or hPD-L2 and their variable region sequences are disclosed. A method of increasing the activity (or reducing downmodulation) of an immune cell through the PD-1 pathway is also disclosed.
1. An isolated polynucleotide encoding an antibody or antibody fragment which binds to human programmed death receptor 1 (PD-1), wherein the antibody or antibody fragment comprises
a. three light chain CDRs having the amino acid sequences set forth in SEQ ID NOs:15, 16 and 17; and/or
b. three heavy chain CDRs having the amino acid sequences set forth in SEQ ID NOs: 18, 19 and 20.
2. The isolated polynucleotide of claim 1 , which comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 21, 22, 23, 24, and 27.
3. An expression vector comprising the polynucleotide of claim 1 .
4. An isolated host cell comprising the expression vector of claim 3 .
5. A method of producing an antibody or antibody fragment that binds to human programmed death receptor 1 (PD-1) comprising:
a. culturing a host cell in culture medium, wherein the host cell comprises the polynucleotide of claim 1 and wherein the host cell is cultured under conditions wherein the antibody or antibody fragment is expressed; and
b. recovering the antibody or antibody fragment from the host cell or culture medium.
6. The isolated polynucleotide of claim 1 , wherein the antibody or antibody fragment comprises a light chain variable region comprising amino acid residues 20 to 130 of SEQ ID NO:32 and a heavy chain variable region comprising amino acid residues 20 to 139 of SEQ ID NO:30.
7. The isolated polynucleotide of claim 6 , wherein the antibody or antibody fragment comprises a light chain comprising amino acid residues 20 to 237 of SEQ ID NO:36 and a heavy chain comprising amino acid residues 20 to 466 of SEQ ID NO:31.
8. An expression vector comprising the polynucleotide of claim 6 .
9. An isolated host cell comprising the expression vector of claim 8 .