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 nucleic acid that encodes the heavy chain of a caninized antibody 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):
(a) wherein CDRL1 comprises the amino acid sequence of SEQ ID NO: 20;
(b) wherein CDRL2 comprises the amino acid sequence comprising SEQ ID NO: 22;
(c) wherein CDRL3 comprises the amino acid sequence of SEQ ID NO: 24;
(d) wherein CDRH1 comprises the amino acid sequence of SEQ ID NO: 14;
(e) wherein CDRH2 comprises the amino acid sequence of SEQ ID NO: 16; and
(f) wherein CDRH3 comprises the amino acid sequence of SEQ ID NO: 18;
wherein the antibody binds canine PD-1 and blocks the binding of canine PD-1 to canine Programmed Cell Death Ligand 1 (PD-L1).
2. The isolated nucleic acid of claim 1 that comprises one or more nucleotide sequences selected from the group consisting of SEQ ID NOs: 13, 15, or 17.
3. The isolated nucleic acid of claim 2 that comprises the nucleotide sequence of SEQ ID NO: 27.
4. An expression vector comprising the isolated nucleic acid of claim 1 .
5. An isolated host cell comprising the expression vector of claim 4 .
6. An isolated nucleic acid that encodes the light chain of a caninized antibody 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):
(a) wherein CDRL1 comprises the amino acid sequence of SEQ ID NO: 20;
(b) wherein CDRL2 comprises the amino acid sequence comprising SEQ ID NO: 22;
(c) wherein CDRL3 comprises the amino acid sequence of SEQ ID NO: 24;
(d) wherein CDRH1 comprises the amino acid sequence of SEQ ID NO: 14;
(e) wherein CDRH2 comprises the amino acid sequence of SEQ ID NO: 16; and
(f) wherein CDRH3 comprises the amino acid sequence of SEQ ID NO: 18;
wherein the antibody binds canine PD-1 and blocks the binding of canine PD-1 to canine Programmed Cell Death Ligand 1 (PD-L1).
7. The isolated nucleic acid of claim 6 that comprises one or more nucleotide sequences selected from the group consisting of SEQ ID NOs: 21, 23, or 25.
8. The isolated nucleic acid of claim 7 that comprises the nucleotide sequence of SEQ ID NO: 33.
9. An expression vector comprising the isolated nucleic acid of claim 6 .
10. An isolated host cell comprising the expression vector of claim 9 .