Pd-l1 antibodies binding canine pd-l1

Abstract

The present invention discloses antibodies including caninized antibodies against canine PD-L1 with specific properties. The present invention further 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. The invention further discloses the use of the caninized anti-canine PD-LI antibodies of the present invention in the treatment of cancer in dogs.

1 - 35 . (canceled) 
     
     
         36 . A nucleic acid that comprises a nucleotide sequence that encodes a set of three heavy chain CDRs comprising the amino acid sequences of SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15. 
     
     
         37 . The nucleic acid of  claim 36 , wherein the nucleotide sequence further encodes 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. 
     
     
         38 . The nucleic acid of  claim 36 , wherein the nucleotide sequence further encodes 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 of the cFc region are substituted for at the indicated positions selected from the group consisting of P4, D31, N63, G64, T65, A93, and P95. 
     
     
         39 . The nucleic acid of  claim 38 , wherein the amino acid sequence comprises amino acid substitutions D31A and N63A, and the amino acid sequence retains P4, G64, T65, A93, and P95. 
     
     
         40 . The nucleic acid of  claim 39 , wherein the nucleotide sequence encodes 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. 
     
     
         41 . The nucleic acid of  claim 39 , wherein the nucleotide sequence encodes 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. 
     
     
         42 . An expression vector comprising the nucleic acid of  claim 41 . 
     
     
         43 . An expression vector comprising the nucleic acid of  claim 40 . 
     
     
         44 . An expression vector comprising the nucleic acid of  claim 39 . 
     
     
         45 . An expression vector comprising the nucleic acid of  claim 38 . 
     
     
         46 . An expression vector comprising the nucleic acid of  claim 37 . 
     
     
         47 . An expression vector comprising the nucleic acid of  claim 36 . 
     
     
         48 . A nucleic acid that comprises a nucleotide sequence that encodes a set of three light chain CDRs comprising the amino acid sequences of SEQ ID NO: 16, SEQ ID NO: 17, and SEQ ID NO: 18. 
     
     
         49 . The nucleic acid of  claim 48 , wherein the nucleotide sequence encodes a canine light chain that comprises the amino acid sequence of SEQ ID NO: 38. 
     
     
         50 . An expression vector comprising the nucleic acid of  claim 49 . 
     
     
         51 . An expression vector comprising the nucleic acid of  claim 48 .