PD-1 binding proteins
View Patent ↗The present invention features PD-1 binding proteins, a subset of which inhibits binding of PD-L1 to the PD-1 receptor. These binding proteins can be employed to modulate the immune system through the manipulation of the PD-1 signaling pathway, enhancing host immunity to treat infections and cancer.
1. An isolated PD-1 binding protein comprising a first variable region and a second variable region, wherein said binding protein specifically binds a human PD-1 epitope contained within a PD-L1-blocking target region, wherein said first variable region is a heavy chain variable (V h ) region comprising:
a first V h CDR comprising either SEQ ID NO:6 or an amino acid sequence differing from SEQ ID NOs:6 by one amino acid;
a second V h CDR comprising either SEQ ID NO:7 or an amino acid sequence differing from SEQ ID NOs:7 by one amino acid; and,
a third V h CDR comprising either SEQ ID NO:8 or an amino acid sequence differing from SEQ ID NOs:8 by one amino acid.
2. The binding protein of claim 1 , wherein said second variable region is a light chain variable (V l ) region comprising:
a first V l CDR comprising either SEQ ID NO:9 or an amino acid sequence differing from SEQ ID NOs:9 by one amino acid;
a second V l CDR comprising either SEQ ID NO:10 or an amino acid sequence differing from SEQ ID NOs:10 by one amino; and
a third V l CDR comprising either SEQ ID NO:11 or an amino acid sequence differing from SEQ ID NOs:11—by one amino acid.
3. The binding protein of claim 1 , wherein
said V h region comprises said first V h CDR consisting of SEQ ID NO:6, said second V h CDR consisting of SEQ ID NO:7, and said third V h CDR consisting of SEQ ID NO:8; and,
said V l region comprises said first V l CDR consisting of SEQ ID NO:9, said second V l CDR consisting of SEQ ID NO:10, and said third V l CDR consisting of SEQ ID NO:11.
4. The binding protein of claim 3 , wherein said binding protein is an antibody.
5. The binding protein of claim 1 , wherein said binding protein is an antibody comprising a first variable region which is a heavy chain variable (V h ) region and a second variable region which is a light chain variable (V l ) region, and wherein said V h region comprises: SEQ ID NO:4 or a humanized SEQ ID NO:4.
6. The binding protein of claim 5 , wherein said V h region comprises SEQ ID NO:4.
7. The binding protein of claim 5 , wherein said V l region comprises SEQ ID NO:5.
8. The binding protein of claim 5 , wherein said binding protein is an antibody and said antibody comprises a heavy chain comprising said V h region and hinge, CH 1 , CH 2 and CH 3 regions from an IgG 1 , IgG 2 , IgG 3 or IgG 4 subtype; and a light chain comprising said V l region and either a human kappa C l or human lambda C l .
9. A pharmaceutical composition comprising the a PD-1 binding protein of claim 1 and a pharmaceutically acceptable carrier.
10. The binding protein of claim 1 , wherein said binding protein is an antibody comprising a first variable region which is a heavy chain variable (V h ) region and a second variable region which is a light chain variable (V l ) region, and wherein said V l region comprises SEQ ID NO:5 or a humanized SEQ ID NO:5.
11. The binding protein of claim 10 , wherein said V l region comprises SEQ ID NO:5.
12. The binding protein of claim 10 , wherein said V h region comprises SEQ ID NO:4.
13. The binding protein of claim 5 , wherein said V h region comprises SEQ ID NO:4 and said V l region comprises SEQ ID NO:5.
14. The binding protein of claim 10 , wherein said binding protein is an antibody and said antibody comprises a heavy chain comprising said V h region and hinge, CH 1 , CH 2 and CH 3 regions from an IgG 1 , IgG 2 , IgG 3 or IgG 4 subtype; and a light chain comprising said V l region and either a human kappa C l or human lambda C l .
15. An isolated PD-1 binding protein comprising a first variable region and a second variable region, wherein said binding protein specifically binds a human PD-1 epitope contained within a PD-L1-blocking target region wherein said first variable region is a light chain variable (V l ) region comprising
a first V l CDR comprising either SEQ ID NO:9 or an amino acid sequence differing from SEQ ID NOs:9 by one amino acid;
a second V l CDR comprising either SEQ ID NO:10 or an amino acid sequence differing from SEQ ID NOs:10 by one amino acid; and,
a third V l CDR comprising either SEQ ID NO:11 or an amino acid sequence differing from SEQ ID NOs:8 by one amino acid.
16. A pharmaceutical composition comprising the a PD-1 binding protein of claim 15 and a pharmaceutically acceptable carrier.
17. An isolated PD-1 binding protein comprising a first variable region and a second variable region, wherein said binding protein specifically binds a human PD-1 epitope contained within a PD-L1-blocking target region, wherein said first variable region is a heavy chain variable (V h ) region of SEQ ID NO:4 and said second variable region is a light chain variable (V l ) region of SEQ ID NO:5.
18. A pharmaceutical composition comprising the a PD-1 binding protein of claim 17 and a pharmaceutically acceptable carrier.
19. A pharmaceutical composition comprising the a PD-1 binding protein of claim 3 and a pharmaceutically acceptable carrier.