Antibodies against canine PD-1
The present invention discloses antibodies to canine PD-1 that have specific sequences and a high binding affinity for canine PD-1. The invention also discloses the use of the antibodies of the present invention in the treatment of cancer in dogs.
1. An isolated mammalian antibody or an antigen binding fragment thereof, that binds canine Programmed Death Receptor 1 (canine PD-1) with specificity, said antibody comprising a set of six complementary determining regions (CDRs) that comprises three light chain CDRs: CDR light 1 (CDRL1), CDR light 2 (CDRL2), and CDR light 3 (CDRL3); and 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: 13;
(b) wherein CDRL2 comprises the amino acid sequence of SEQ ID NO: 19;
(c) wherein CDRL3 comprises the amino acid sequence of SEQ ID NO: 25;
(d) wherein CDRH1 comprises the amino acid sequence of SEQ ID NO: 27;
(e) wherein CDRH2 comprises the amino acid sequence of SEQ ID NO: 31; and
(f) wherein CDRH3 comprises the amino acid sequence of SEQ ID NO: 36.
2. The isolated mammalian antibody or antigen binding fragment thereof of claim 1 , wherein the mammalian antibody is a murine antibody.
3. The isolated mammalian antibody or antigen binding fragment thereof of claim 2 that is a caninized antibody.
4. The isolated mammalian antibody or antigen binding fragment thereof of claim 3 , wherein when bound to canine PD-1, said antibody binds to at least one amino acid residue within SEQ ID NO: 103; wherein the antibody and antigen binding fragment thereof binds canine PD-1 and blocks the binding of canine PD-1 to canine Programmed Death Ligand 1 (PD-L1).
5. The isolated mammalian antibody or antigen binding fragment thereof of claim 4 wherein when bound to canine PD-1 said antibody binds to at least one amino acid residue within one or more amino acid sequences selected from the group consisting of SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 99, SEQ ID NO: 100, of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 104.
6. The isolated mammalian antibody or antigen binding fragment thereof of claim 5 , wherein when bound to canine PD-1 said antibody binds to one or more amino acid residues selected from the group consisting of R 62 , R 69 , R 72 , R 75 , and R 90 of SEQ ID NO: 2.
7. An isolated nucleic acid that encodes the light chain of the antibody of claim 1 .
8. An isolated nucleic acid that encodes the heavy chain of the antibody of claim 1 .
9. An isolated nucleic acid that encodes the amino acid sequences of SEQ ID NOs: 27, 31, and 36.
10. An expression vector comprising the isolated nucleic acid of claim 8 .
11. A pharmaceutical composition comprising the antibody of claim 4 and a pharmaceutically acceptable carrier or diluent.
12. A method of increasing the activity of an immune cell, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 11 .
13. A pharmaceutical composition comprising the antibody of claim 3 and a pharmaceutically acceptable carrier or diluent.
14. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier or diluent.
15. An expression vector comprising the isolated nucleic acid of claim 7 .
16. A method of increasing the activity of an immune cell, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 14 .
17. A method of increasing the activity of an immune cell, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 13 .