PD-L1 antibodies binding canine PD-L1
The present disclosure describes antibodies including caninized antibodies against canine PD-L1 with specific properties. The document relates to epitopes of canine PD-L1 that bind to these antibodies, as well as to anti-canine PD-L1 antibodies that bind these epitopes, and to the use of the caninized anti-canine PD-L1 antibodies in the treatment of cancer in dogs.
1. An isolated antibody or antigen binding fragment thereof that binds canine Programmed Death Ligand 1 (canine PD-L1) comprising
(a) a CDRL1 that comprises the amino acid sequence of SEQ ID NO: 16;
(b) a CDRL2 that comprises the amino acid sequence of SEQ ID NO: 17;
(c) a CDRL3 that comprises the amino acid sequence of SEQ ID NO: 18;
(d) a CDRH1 that comprises the amino acid sequence of SEQ ID NO: 13;
(e) a CDRH2 that comprises the amino acid sequence of SEQ ID NO: 14; and
(f) a CDRH3 that comprises the amino acid sequence of SEQ ID NO: 15;
wherein the antibody and antigen binding fragment thereof bind canine PD-L1 and block the binding of canine PD-L1 to canine Programmed Death 1 (PD-1).
2. The isolated antibody of claim 1 , wherein the antibody is a caninized antibody or antigen binding fragment thereof.
3. The caninized antibody or antigen binding fragment thereof of claim 2 that comprises a canine fragment crystallizable region (cFc region) that comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 66 and SEQ ID NO: 68; wherein one to seven amino acid residues are substituted for at the indicated positions selected from the group consisting of P4, D31, N63, G64, T65, A93, and P95.
4. The caninized antibody of claim 3 or antigen binding fragment thereof, wherein there are two substitutions, D31A and N63A, and the amino acid sequence retains P4, G64, T65, A93, and P95.
5. The caninized antibody or antigen binding fragment thereof of claim 4 further comprising a canine light chain that comprises the amino acid sequence of SEQ ID NO: 38.
6. A pharmaceutical composition comprising the antibody of claim 5 or antigen binding fragment thereof and a pharmaceutically acceptable carrier or diluent.
7. The caninized antibody of claim 4 that comprises the amino acid sequence of SEQ ID NO: 26, wherein there is a proline residue at amino acid position 242, an alanine residue at amino acid position 269, an alanine residue at amino acid position 301, a glycine residue at amino acid position 302, a threonine residue at amino acid position 303, an alanine residue at amino acid position 331, and a proline residue at amino acid position 333.
8. The caninized antibody of claim 7 further comprising a canine light chain that comprises the amino acid sequence of SEQ ID NO: 38.
9. A pharmaceutical composition comprising the antibody of claim 8 and a pharmaceutically acceptable carrier or diluent.
10. The caninized antibody of claim 4 that comprises the amino acid sequence of SEQ ID NO: 28, wherein there is a proline residue at amino acid position 240, an alanine residue at amino acid position 267, an alanine residue at amino acid position 299, a glycine residue at amino acid position 300, a threonine residue at amino acid position 301, an alanine residue at amino acid position 329, and a proline residue at amino acid position 331.
11. The caninized antibody of claim 10 further comprising a canine light chain that comprises the amino acid sequence of SEQ ID NO: 38.
12. A pharmaceutical composition comprising the antibody of claim 8 and a pharmaceutically acceptable carrier or diluent.