Antibodies to human programmed death receptor PD-1
AssigneeMSD Oss B.V.
InventorsGregory John Carven, Hans van Eenennaam, Gradus Johannes Dulos
Life of this patent
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Abstract
Antibodies which block the binding of human Programmed Death Receptor 1 (hPD-1) to its ligands (hPD-L1 or hPD-L2) and their variable region sequences are disclosed. A method of increasing the activity (or reducing downmodulation) of an immune response through the PD-I pathway is also disclosed.
Claims11
An isolated antibody or antibody fragment which binds to human PD-1 comprising:
- a. three light chain CDRs of 15, 16 and 17;
- and/or
- b. three heavy chain CDRs of SEQ ID NOs:
- 18, 19 and 20.
An isolated antibody or antibody fragment which competes for a binding epitope on PD-1 with an antibody or antibody fragment comprising three light chain CDRs of SEQ ID NOs:
- 15, 16 and 17 and three heavy chain CDRs of SEQ ID NOs:
- 18, 19 and 20, wherein said competing antibody or antibody fragment has at least one of the following characteristics:
- a. binds human PD-1 with a KD of about 100 pM or lower;
- b. binds human PD-1 with a KD of about 30 pM or lower;
- c. binds to human PD-1 with about the same KD as an antibody having a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 31 and a light chain comprising the amino acid sequence of SEQ ID NO:
- 32;
- d. binds to human PD-1 with about the same KD as an antibody having a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 31 and a light chain comprising the amino acid sequence of SEQ ID NO:
- 33;
- e. binds to human PD-1 with a kassoc of about 7.5×105 l/M·s or faster;
- f. binds to human PD-1 with a kassoc of about 1×106 l/M·s or faster;
- g. binds to human PD-1 with a kdissoc of about 2×10-5 l/s or slower;
- h. binds to human PD-1 with a kdissoc of about 2.7×10-5 l/s or slower;
- i. binds to human PD-1 with a kdissoc of about 3×10-5 l/s or slower;
- or
- j. blocks binding of human PD-L1 or human PD-L2 to human PD-1 with an IC50 of about 1 nM or lower.
An isolated antibody comprising a heavy chain comprising amino acid residues 20 to 446 of SEQ ID NO:
- 31 and a light chain comprising amino acid residues of 20-237 of SEQ ID NO:
- 36.
Dependencies are inferred from the claim text.