A monoclonal antibody or an antigen-binding portion thereof, which cross-competes for binding to PD-1 with a reference antibody or antigen-binding portion thereof comprising a heavy chain variable region that comprises CDR1, CDR2, and CDR3 domains and a light chain variable region that comprises CDR1, CDR2, and CDR3 domains selected from the group consisting of:
- (a) a heavy chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:
- 15;
- a heavy chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:
- 22;
- a heavy chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:
- 29;
- a light chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:
- 36;
- a light chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:
- 43;
- and a light chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:
- 50;
- (b) a heavy chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:
- 16;
- a heavy chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:
- 23;
- a heavy chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:
- 30;
- a light chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:
- 37;
- a light chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:
- 44;
- and a light chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:
- 51;
- (c) a heavy chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:
- 17;
- a heavy chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:
- 24;
- a heavy chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:
- 31;
- a light chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:
- 38;
- a light chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:
- 45;
- and a light chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:
- 52;
- (d) a heavy chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:
- 18;
- a heavy chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:
- 25;
- a heavy chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:
- 32;
- a light chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:
- 39;
- a light chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:
- 46;
- and a light chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:
- 53;
- (e) a heavy chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:
- 19;
- a heavy chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:
- 26;
- a heavy chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:
- 33;
- a light chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:
- 40;
- a light chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:
- 47;
- and a light chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:
- 54;
- (f) a heavy chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:
- 20;
- a heavy chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:
- 27;
- a heavy chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:
- 34;
- a light chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:
- 41;
- a light chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:
- 48;
- and a light chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:
- 55;
- and
- (g) a heavy chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:
- 21;
- a heavy chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:
- 28;
- a heavy chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:
- 35;
- a light chain CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:
- 42;
- a light chain CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:
- 49;
- and a light chain CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:
- 56, and wherein the monoclonal antibody or antigen-binding portion thereof exhibits at least one of the following properties:
- (i) binds to human PD-1 with a KD of 1×10−7 M or less, wherein the KD is measured by surface plasmon resonance (Biacore) analysis;
- (ii) binds to human PD-1 with an on rate (kon) of about 0.76×105 l/Ms or more, wherein the on rate (kon) is measured by surface plasmon resonance (Biacore) analysis;
- and
- (iii) binds to human PD-1 with an off rate (koff) of about 4.5×10−−4 l/s or less, wherein the off rate (koff) is measured by surface plasmon resonance (Biacore) analysis.