Monoclonal Antibodies to Programmed Death 1 (PD-1)

An isolated monoclonal antibody, or antigen-binding portion thereof, comprising a heavy chain variable region that comprises CDR1, CDR2, and CDR3 sequences;

• and a light chain variable region that comprises CDR1, CDR2, and CDR3 sequences, wherein:
• a) the heavy chain variable region CDR3 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
• 29, 30, 31, 32, 33, 34 and 35, and conservative modifications thereof,
• b) the light chain variable region CDR3 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
• 50, 51, 52, 53, 54, 55 and 56, and conservative modifications thereof, and
• c) the antibody or the antigen-binding portion thereof specifically binds to PD-1.

A method for preparing an anti-PD-1 antibody comprising:

• (a) providing:
• (i) a heavy chain variable region antibody sequence comprising a CDR1 sequence that is selected from the group consisting of SEQ ID NOs:
• 15, 16, 17, 18, 19, 20 and 21, a CDR2 sequence that is selected from the group consisting of SEQ ID NOs:
• 22, 23, 24, 25, 26, 27 and 28;
• and a CDR3 sequence that is selected from the group consisting of SEQ ID NOs:
• 29, 30, 31, 32, 33, 34 and 35;
• or (ii) a light chain variable region antibody sequence comprising a CDR1 sequence that is selected from the group consisting of SEQ ID NOs:
• 36, 37, 38, 39, 40, 41 and 42, a CDR2 sequence that is selected from the group consisting of SEQ ID NOs:
• 43, 44, 45, 46, 47, 48 and 49, and a CDR3 sequence that is selected from the group consisting of SEQ ID NOs:
• 50, 51, 52, 53, 54, 55 and 56;
• (b) altering at least one amino acid residue within at least one variable region antibody sequence, said sequence being selected from the heavy chain variable region antibody sequence and the light chain variable region antibody sequence, to create at least one altered antibody sequence;
• and
• (c) expressing the altered antibody sequence as a protein.