Immunological reagents
AssigneeMabQuest SA
InventorsGiuseppe Pantaleo, Craig Fenwick
Life of this patent
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Abstract
This disclosure relates to binding agents with specificity for programmed cell death 1 (PD-1) and to methods for using the same to treat, prevent and/or ameliorate an infectious disease (e.g., human immunodeficiency virus (HIV)), cancer and/or autoimmunity. In addition, this disclosure identifies a novel binding patch (“P2”) on PD-1 that is linked with a previously unidentified functional activity of PD-1 that is distinct from the interaction site involved with either the PD-L1 or PD-L2 ligands. Furthermore, we demonstrate that antibodies that interact with this region of PD-1 are able to act as antagonists of PD-1 and that this antagonism is further enhanced with the addition of antibodies that act through the blockade of the PD-1/PD-L1/L2 interaction.
Claims29
A humanized antibody or fragment thereof that binds human PD-1 and comprises a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:
- 176 and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 190.
An isolated polynucleotide encoding a humanized antibody or fragment thereof that binds human PD-1 and comprises a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO:
- 176 and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO:
- 190.
An isolated polynucleotide comprising the nucleic acid sequence set forth in SEQ ID NO:
- 229 or SEQ ID NO:
- 243.
A humanized antibody or fragment thereof that binds human PD-1 and comprises a combination of a heavy chain variable region (VH) and a light chain variable region (VL), wherein the humanized antibody comprises:
- (a) a VH comprising an amino acid sequence as set forth in one of SEQ ID NOS:
- 147-150 and a VL comprising an amino acid sequence set forth in one of SEQ ID NOS:
- 159-163;
- or
- (b) a VH comprising an amino acid sequence as set forth in one of SEQ ID NOS:
- 172-177 and a VL comprising an amino acid sequence as set forth in one of SEQ ID NOS:
- 186-190.
An isolated polynucleotide encoding a humanized antibody or fragment that binds human PD-1 and comprises a combination of a heavy chain variable region (VH) and a light chain variable region (VL), wherein the humanized antibody comprises:
- (a) a VH encoded by a nucleic acid sequence as set forth in one of SEQ ID NOS:
- 200-203 and a VL encoded by a nucleic acid sequence as set forth in one of SEQ ID NOS:
- 212-216;
- or
- (b) a VH encoded by a nucleic acid sequence as set forth in one of SEQ ID NOS:
- 225-230 and a VL encoded by a nucleic acid sequence as set forth in one of SEQ ID NOS:
- 239-243.
Dependencies are inferred from the claim text.