Caninized murine antibodies to human PD-1
The present invention provides caninized murine anti-human PD-1 antibodies that have specific sequences and a high binding affinity for canine PD-1. The invention also relates to use of these antibodies in the treatment of dogs.
1. An isolated caninized antibody or antigen binding fragment thereof that specifically binds Programmed Cell Death Receptor 1 (PD-1) comprising a canine IgG heavy chain and a canine kappa light chain; wherein the canine kappa light chain comprises three light chain complementary determining regions (CDRs): CDR light 1 (CDRL1), CDR light 2 (CDRL2), and CDR light 3 (CDRL3); and the canine IgG heavy chain comprises three heavy chain CDRs: CDR heavy 1 (CDRH1), CDR heavy 2 (CDRH2) and CDR heavy 3 (CDRH3):
wherein CDRL1 comprises the amino acid sequence of SEQ ID NO: 20; CDRL2 comprises the amino acid sequence of SEQ ID NO: 22; CDRL3 comprises the amino acid sequence of SEQ ID NO: 24;
wherein CDRH1 comprises the amino acid sequence of SEQ ID NO: 14; CDRH2 comprises the amino acid sequence of SEQ ID NO: 16; CDRH3 comprises the amino acid sequence of SEQ ID NO: 18;
wherein the IgG heavy chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 26, SEQ ID NO: 28, and SEQ ID NO: 30; and
wherein the antibody and fragment bind canine PD-1 and block the binding of canine PD-1 to canine Programmed Cell Death Ligand 1 (PD-L1).
2. The isolated caninized antibody of claim 1 , wherein the kappa light chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 32 and SEQ ID NO: 34.
3. The isolated caninized antibody of claim 2 , comprising the amino acid sequence of SEQ ID NO: 28 and of SEQ ID NO: 34.
4. A pharmaceutical composition comprising the antibody or antigen binding fragment of claim 3 and a pharmaceutically acceptable carrier or diluent.