Therapeutic antibodies

HK40135705APending Publication Date: 2026-07-31ZOETIS SERVICES UK LTD
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Patent Information

Application Number
HK62026123750
Authority / Receiving Office
HK · HK
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-07-14
Filing Date
2026-05-21
Publication Date
2026-07-31

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Abstract

The disclosure provides an isolated canine antibody or antigen-binding portion thereof which binds to an epitope of the extracellular domain of canine PD-1, compositions comprising the same and methods of their use.
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Description

Abstract This disclosure provides an isolated canine antibody or its antigen-binding moiety that binds to an epitope of the extracellular domain of canine PD-1; a composition comprising the isolated canine antibody or its antigen-binding moiety; and methods of using the thereof.

Claims

Claims1. An isolated canine antibody or antigen-binding portion thereof which binds to one of the following epitopes of the extracellular domain of canine PD-1 : i) an epitope comprising T76, Q83, E84, L128, P129, P130 according to SEQ ID NO: 2 ii) an epitope comprising D58, D61 , N74, T76, Y127 according to SEQ ID NO: 2 wherein the epitope is determined using an epitope mapping technique.

2. The antibody or antigen binding portion thereof according to claim 1 , wherein said antibody comprises a) an HC CDR1 sequence comprising or consisting of SEQ ID NO: 17 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 17 and an HC CDR2 sequence comprising or consisting of SEQ ID NO: 18 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 18 and an HC CDR3 sequence comprising or consisting of SEQ ID NO: 19 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 19 and an LC CDR1 sequence comprising or consisting of SEQ ID NO: 20 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 20 and an LC CDR2 sequence comprising or consisting of SEQ ID NO: 21 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 21 and an LC CDR3 sequence comprising or consisting of SEQ ID NO: 22 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 22; or b) an HC CDR1 sequence comprising or consisting of SEQ ID NO: 27 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 27 and an HC CDR2 sequence comprising or consisting of SEQ ID NO: 28 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 28 and an HC CDR3 sequence comprising or consisting of SEQ ID NO: 29 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 29 and an LC CDR1 sequence comprising or consisting of SEQ ID NO: 30 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 30 and an LC CDR2 sequence comprising or consisting of SEQ ID NO: 31 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 31 and an LC CDR3 sequence comprising or consisting of SEQ ID NO: 32 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 32; or c) an HC CDR1 sequence comprising or consisting of SEQ ID NO: 207 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 207 and an HC CDR2 sequence comprising or consisting of SEQ ID NO: 208 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 208 and an HC CDR3 sequence comprising or consisting of SEQ ID NO: 209 or an amino acid sequence w with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 209 and an LC CDR1 sequence comprising or consisting of SEQID NO: 210 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 210 and an LC CDR2 sequence comprising or consisting of SEQ ID NO: 211 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 211 and an LC CDR3 sequence comprising or consisting of SEQ ID NO: 212 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 212; or d) an HC CDR1 sequence comprising or consisting of SEQ ID NO: 97 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 97 and an HC CDR2 sequence comprising or consisting of SEQ ID NO: 98 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 98 and an HC CDR3 sequence comprising or consisting of SEQ ID NO: 99 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 99 and an LC CDR1 sequence comprising or consisting of SEQ ID NO: 100 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 100 and an LC CDR2 sequence comprising or consisting of SEQ ID NO: 101 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 101 and an LC CDR3 sequence comprising or consisting of SEQ ID NO: 102 or an amino acid sequence with at least 70%, 80%, 85%, 90% or 95% sequence identity to SEQ ID NO: 102.

3. The antibody or antigen-binding portion thereof according to claim 1 or 2, wherein said antibody comprises a) an HC CDR1 sequence comprising or consisting of SEQ ID NO: 17 or an amino acid sequence which has 1 , 2, 3, 4, or 5 amino acid differences compared to SEQ ID NO: 17 and an HC CDR2 sequence comprising or consisting of SEQ ID NO: 18 or an amino acid sequence which has 1 , 2, 3, 4, 5, or 6 amino acid differences compared to SEQ ID NO: 18 and an HC CDR3 sequence comprising or consisting of SEQ ID NO: 19 or an amino acid sequence which has 1 , 2, 3, 4, 5, 6, 7, 8, or 9 amino acid differences compared to SEQ ID NO: 19 and an LC CDR1 sequence comprising or consisting of SEQ ID NO: 20 or an amino acid sequence which has 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13 or 14 amino acid differences compared to SEQ ID NO: 20 and an LC CDR2 sequence comprising or consisting of SEQ ID NO: 21 or an amino acid sequence which has 1 , 2, 3, 4, or 5 amino acid differences compared to SEQ ID NO: 21 and an LC CDR3 sequence comprising or consisting of SEQ ID NO: 22 or an amino acid sequence which has 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid differences compared to SEQ ID NO: 22; or b) an HC CDR1 sequence comprising or consisting of SEQ ID NO: 207 or an amino acid sequence which has 1 , or 2 amino acid differences compared to SEQ ID NO: 207 and an HC CDR2 sequence comprising or consisting of SEQ ID NO: 208 or an amino acid sequence which has 1 , 2, 3, 4, or 5 amino acid differences compared to SEQ ID NO: 208 and an HC CDR3 sequence comprising or consisting of SEQ ID NO: 209 or an amino acid sequence which has 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, or 16 amino acid differences compared to SEQ ID NO: 209 and an LC CDR1 sequence comprising or consisting of SEQ ID NO: 210 or an amino acid sequence which has 1 , 2 or 3 amino acid differences compared to SEQ ID NO: 210 and an LC CDR2 sequence comprising or consisting of SEQ ID NO: 211 or an amino acid sequence which has 1 or 2 amino acid differences compared to SEQ ID NO: 211 andan LC CDR3 sequence comprising or consisting of SEQ ID NO: 212 or an amino acid sequence which has 1 , 2, 3, or 4 amino acid differences compared to SEQ ID NO: 212; or c) an HC CDR1 sequence comprising or consisting of SEQ ID NO: 97 or an amino acid sequence which has 1 , 2, or 3 amino acid differences compared to SEQ ID NO: 97 and an HC CDR2 sequence comprising or consisting of SEQ ID NO: 98 or an amino acid sequence which has 1 , 2, 3, or 4 amino acid differences compared to SEQ ID NO: 98 and an HC CDR3 sequence comprising or consisting of SEQ ID NO: 99 or an amino acid sequence which has 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, or 14 amino acid differences compared to SEQ ID NO: 99 and an LC CDR1 sequence comprising or consisting of SEQ ID NO: 100 or an amino acid sequence which has 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14 or 15 amino acid differences compared to SEQ ID NO: 100 and an LC CDR2 sequence comprising or consisting of SEQ ID NO: 101 or an amino acid sequence which has 1 , 2, 3, 4, or 5 amino acid differences compared to SEQ ID NO: 101 and an LC CDR3 sequence comprising or consisting of SEQ ID NO: 102 or an amino acid sequence which has 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid differences compared to SEQ ID NO: 102.

4. An isolated canine antibody or antigen-binding portion thereof which binds canine PD-1 wherein said antibody comprises a) an HC CDR1 sequence comprising or consisting of SEQ ID NO: 17 or an amino acid sequence which has 1 , 2, 3, 4, or 5 amino acid differences compared to SEQ ID NO: 17 and an HC CDR2 sequence comprising or consisting of SEQ ID NO: 18 or an amino acid sequence which has 1 , 2, 3, 4, 5, or 6 amino acid differences compared to SEQ ID NO: 18 and an HC CDR3 sequence comprising or consisting of SEQ ID NO: 19 or an amino acid sequence which has 1 , 2, 3, 4, 5, 6, 7, 8, or 9 amino acid differences compared to SEQ ID NO: 19 and an LC CDR1 sequence comprising or consisting of SEQ ID NO: 20 or an amino acid sequence which has 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13 or 14 amino acid differences compared to SEQ ID NO: 20 and an LC CDR2 sequence comprising or consisting of SEQ ID NO: 21 or an amino acid sequence which has 1 , 2, 3, 4, or 5 amino acid differences compared to SEQ ID NO: 21 and an LC CDR3 sequence comprising or consisting of SEQ ID NO: 22 or an amino acid sequence which has 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid differences compared to SEQ ID NO: 22; or b) an HC CDR1 sequence comprising or consisting of SEQ ID NO: 207 or an amino acid sequence which has 1 , or 2 amino acid differences compared to SEQ ID NO: 207 and an HC CDR2 sequence comprising or consisting of SEQ ID NO: 208 or an amino acid sequence which has 1 , 2, 3, 4, or 5 amino acid differences compared to SEQ ID NO: 208 and an HC CDR3 sequence comprising or consisting of SEQ ID NO: 209 or an amino acid sequence which has 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, or 16 amino acid differences compared to SEQ ID NO: 209 and an LC CDR1 sequence comprising or consisting of SEQ ID NO: 210 or an amino acid sequence which has 1 , 2 or 3 amino acid differences compared to SEQ ID NO: 210 and an LC CDR2 sequence comprising or consisting of SEQ ID NO: 211 or an amino acid sequence which has 1 or 2 amino acid differences compared to SEQ ID NO: 211 and an LC CDR3 sequence comprising or consisting of SEQ ID NO: 212 or an amino acid sequence which has 1 , 2, 3, or 4 amino acid differences compared to SEQ ID NO: 212; orc) an HC CDR1 sequence comprising or consisting of SEQ ID NO: 97 or an amino acid sequence which has 1 , 2, or 3 amino acid differences compared to SEQ ID NO: 97 and an HC CDR2 sequence comprising or consisting of SEQ ID NO: 98 or an amino acid sequence which has 1 , 2, 3, or 4 amino acid differences compared to SEQ ID NO: 98 and an HC CDR3 sequence comprising or consisting of SEQ ID NO: 99 or an amino acid sequence which has 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, or 14 amino acid differences compared to SEQ ID NO: 99 and an LC CDR1 sequence comprising or consisting of SEQ ID NO: 100 or an amino acid sequence which has 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14 or 15 amino acid differences compared to SEQ ID NO: 100 and an LC CDR2 sequence comprising or consisting of SEQ ID NO: 101 or an amino acid sequence which has 1 , 2, 3, 4, or 5 amino acid differences compared to SEQ ID NO: 101 and an LC CDR3 sequence comprising or consisting of SEQ ID NO: 102 or an amino acid sequence which has 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid differences compared to SEQ ID NO: 102.

5. The antibody or antigen-binding portion thereof according to any preceding claim wherein said antibody or antigen-binding portion thereof has i) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 17, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 18, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 19, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 20, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 21 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 22, ii) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 27, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 28, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 29, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 30, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 31 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 32 iii) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 7, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 8, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 9, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 10, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 11 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 12, iv) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 37, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 38, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 39, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 40, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 41 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 42 v) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 47, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 48, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 49, a LC CDR1 sequence comprising SEQ ID NO: 50, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 51 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 52, vi) a HC CDR1 sequence comprising SEQ ID NO: 57, a HC CDR2 sequence comprising SEQ ID NO: 58, a HC CDR3 sequence comprising SEQ ID NO: 59, a LC CDR1 sequence comprising SEQ ID NO: 60, a LC CDR2 sequence comprising SEQ ID NO: 61 and a LC CDR3 sequence comprising SEQ ID NO: 62,vii) a HC CDR1 sequence comprising SEQ ID NO: 67, a HC CDR2 sequence comprising SEQ ID NO: 68, a HC CDR3 sequence comprising SEQ ID NO: 69, a LC CDR1 sequence comprising SEQ ID NO: 70, a LC CDR2 sequence comprising SEQ ID NO: 71 and a LC CDR3 sequence comprising SEQ ID NO: 72, viii) a HC CDR1 sequence comprising SEQ ID NO: 77, a HC CDR2 sequence comprising SEQ ID NO: 78, a HC CDR3 sequence comprising SEQ ID NO: 79, a LC CDR1 sequence comprising SEQ ID NO: 80, a LC CDR2 sequence comprising SEQ ID NO: 81 and a LC CDR3 sequence comprising SEQ ID NO: 82, ix) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 87, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 88, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 89, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 90, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 91 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 92, x) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 97, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 98, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 99, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 100, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 101 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 102, xi) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 107, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 108, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 109, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 110, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 111 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 112, xii) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 117, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 118, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 119, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 120, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 12 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 122, xiii) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 127, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 128, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 129, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 130, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 131 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 132, xiv) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 137, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 138, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 139, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 140, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 141 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 142, xv) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 147, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 148, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 149, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 150, a LC CDR2 sequencecomprising or consisting of SEQ ID NO: 151 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 152, xvi) a HO CDR1 sequence comprising or consisting of SEQ ID NO: 157, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 158, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 159, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 160, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 161 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 162, xvii) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 167, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 168, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 169, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 170, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 171 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 172, xviii) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 177, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 178, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 179, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 180, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 181 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 182, xix) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 187, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 188, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 189, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 190, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 191 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 192, xx) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 197, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 198, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 199, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 200, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 201 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 202, xxi) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 207, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 208, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 209, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 210, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 211 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 212, xxii) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 217, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 218, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 219, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 220, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 221 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 222, xxiii) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 227, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 228, a HC CDR3 sequence comprising or consisting of SEQ IDNO: 229, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 230, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 231 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 232, xxiv) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 237, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 238, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 239, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 240, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 241 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 242, xxv) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 247, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 248, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 249, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 250, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 251 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 252, xxvi) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 257, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 258, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 259, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 260, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 261 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 262, xxvii) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 267, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 268, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 269, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 270, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 271 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 272, xxviii) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 277, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 278, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 279, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 280, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 281 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 282, or xxix) a HC CDR1 sequence comprising or consisting of SEQ ID NO: 287, a HC CDR2 sequence comprising or consisting of SEQ ID NO: 288, a HC CDR3 sequence comprising or consisting of SEQ ID NO: 289, a LC CDR1 sequence comprising or consisting of SEQ ID NO: 290, a LC CDR2 sequence comprising or consisting of SEQ ID NO: 291 and a LC CDR3 sequence comprising or consisting of SEQ ID NO: 292.

6. The antibody or antigen-binding portion thereof according to a preceding claim wherein said antibody or antigen-binding portion thereof comprises a HC variable region sequence comprising SEQ ID NO: 4 or a sequence with at least 45%, 50%, 60%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 6 or a sequence with at least 35%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90% or95% sequence identity thereto for example a LC variable region sequence comprising SEQ ID NO: 6.

7. The antibody or antigen-binding portion thereof according to a preceding claim wherein said antibody or antigen-binding portion thereof has a) a HC variable region sequence comprising SEQ ID NO: 4 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 6 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or b) a HC variable region sequence comprising SEQ ID NO: 14 or a sequence with at least 40%, 45%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 16 or a sequence with at least 35%, 45%, 55%, 65%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or c) a HC variable region sequence comprising SEQ ID NO: 24 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 6 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or d) a HC variable region sequence comprising SEQ ID NO: 34 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 6 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or e) a HC variable region sequence comprising SEQ ID NO: 44 or a sequence with at least 40%, 50%, 60%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 46 or a sequence with at least 35%, 45%, 55%, 65%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or f) a HC variable region sequence comprising SEQ ID NO: 54 or a sequence with at least 40%, 45%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 56 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or g) a HC variable region sequence comprising SEQ ID NO: 64 or a sequence with at least 45%, 65%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 36 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or h) a HC variable region sequence comprising SEQ ID NO: 74 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 6 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or i) a HC variable region sequence comprising SEQ ID NO: 84 or a sequence with at least 40%, 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 86 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; orj) a HC variable region sequence comprising SEQ ID NO: 94 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 6 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or k) a HC variable region sequence comprising SEQ ID NO: 104 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 6 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or l) a HC variable region sequence comprising SEQ ID NO: 114 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 6 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or m) a HC variable region sequence comprising SEQ ID NO: 124 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 6 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or n) a HC variable region sequence comprising SEQ ID NO: 134 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 136 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or o) a HC variable region sequence comprising SEQ ID NO:144 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 6 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or p) a HC variable region sequence comprising SEQ ID NO: 154 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 156 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or q) a HC variable region sequence comprising SEQ ID NO: 164 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 176 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or r) a HC variable region sequence comprising SEQ ID NO: 174 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 6 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or s) a HC variable region sequence comprising SEQ ID NO: 184 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequencecomprising SEQ ID NO: 186 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or t) a HC variable region sequence comprising SEQ ID NO: 194 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 6 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or u) a HC variable region sequence comprising SEQ ID NO: 204 or a sequence with at least 40%, 45%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 206 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or v) a HC variable region sequence comprising SEQ ID NO: 214 or a sequence with at least 40%, 45%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 216 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or w) a HC variable region sequence comprising SEQ ID NO: 224 or a sequence with at least 40%, 45%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 226 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or x) a HC variable region sequence comprising SEQ ID NO: 234 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 236 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or y) a HC variable region sequence comprising SEQ ID NO: 244 or a sequence with at least 40%, 45%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 246 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or z) a HC variable region sequence comprising SEQ ID NO: 254 or a sequence with at least 40%, 45%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 256 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or aa) a HC variable region sequence comprising SEQ ID NO: 264 or a sequence with at least 40%, 45%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 266 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or bb) a HC variable region sequence comprising SEQ ID NO: 274 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 276 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; orcc) a HC variable region sequence comprising SEQ ID NO: 284 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 286 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto; or dd) a HC variable region sequence comprising SEQ ID NO: 24 or a sequence with at least 45%, 50%, 70%, 75%, 80%, 85% or 90% sequence identity thereto and a LC variable region sequence comprising SEQ ID NO: 26 or a sequence with at least 35%, 40%, 70%, 75%, 80%, 85% or 90% sequence identity thereto.

8. The antibody or antigen-binding portion thereof according to a preceding claim wherein said antigen-binding portion thereof is an scFv, Fv, heavy chain or single domain antibody.

9. An isolated canine antibody or antigen-binding portion thereof according to a preceding claim that binds to canine PD-1 wherein said antibody or antigen-binding portion thereof that competes with PD-L1 and / or PD-L2.

10. The antibody or antigen-binding portion thereof according to a preceding claim wherein said antibody or antigen binding portion thereof blocks the interaction of PD-1 with PD-L1 and / or PD-L2 and / or prevents a cellular response associated with the interaction of PD-1 with PD-L1 and / or PD-L2.

11. The antibody or antigen-binding portion thereof according to a preceding claim wherein said antibody or antigen-binding portion thereof is conjugated to a therapeutic moiety.

12. The antibody or antigen-binding portion thereof according to claim 11 wherein said therapeutic moiety is a second antibody or antigen-binding portion thereof.

13. The antibody or antigen-binding portion thereof according to claim 12 wherein said second antibody or antigen-binding portion thereof binds to a different target.

14. The antibody or antigen-binding portion thereof according to a preceding claim wherein said antibody or antigen-binding portion thereof is conjugated to a further moiety selected from a half-life extending moiety, label, cytotoxin, liposome, nanoparticle or radioisotope.

15. The antibody or antigen-binding portion thereof according to claim 14 wherein the half-life extending moiety is selected from: albumin binding moiety, a transferrin binding moiety, a polyethylene glycol molecule, a recombinant polyethylene glycol molecule, human serum albumin, a fragment of human serum albumin, an albumin binding peptide or single domain antibody that binds to human serum albumin.

16. A pharmaceutical composition comprising an antibody or antigen-binding portion thereof according to a preceding claim.

17. The antibody or antigen-binding portion thereof according to any of claims 1 to 15 or the pharmaceutical composition according to claim 16 for use in the treatment of disease.

18. A method of treating a disease in a canine subject in need thereof comprising administering an effective amount of the antibody or antigen-binding portion thereof of any one of claims 1 to 15 or a pharmaceutical composition according to claim 16.

19. The antibody or antigen-binding portion thereof or the pharmaceutical composition according to claim 17 or the method of claim 18 wherein the disease is a cancer or tumor.

20. The antibody or antigen-binding portion thereof or the pharmaceutical composition according to claim 17 or 19 or the method of claim 18 or 19 further comprising separately administering another therapeutic agent to the subject.

21. The antibody or antigen-binding portion thereof or the pharmaceutical composition, or the method according to claim 20 wherein the therapeutic agent is a cytotoxic agent or a radiotoxic agent, an immunosuppressant, an immunological modulating agent, or an antibody or antibody fragment thereof.

22. The antibody or antigen-binding portion thereof or the pharmaceutical composition, or the method according to claim 21 wherein the immunological modulating agent is a cytokine or a chemokine.

23. A nucleic acid sequence that encodes an antibody or antibody antigen-binding portion thereof according to any one of claims 1 to 15.

24. The nucleic acid sequence according to claim 23 comprising a sequence selected from: SEQ ID NO: 3 and SEQ ID NO: 5, or SEQ ID NO: 13 and SEQ ID NO: 15, or SEQ ID NO: 23 and SEQ ID NO: 25, or SEQ ID NO: 33 and SEQ ID NO: 35, or SEQ ID NO: 43 and SEQ ID NO: 45, or SEQ ID NO: 53 and SEQ ID NO: 55, or SEQ ID NO: 63 and SEQ ID NO: 65, or SEQ ID NO: 73 and SEQ ID NO: 75, or SEQ ID NO: 83 and SEQ ID NO: 85, or SEQ ID NO: 93 and SEQ ID NO: 95, or SEQ ID NO: 103 and SEQ ID NO: 105, or SEQ ID NO: 113 and SEQ ID NO: 115, or SEQ ID NO: 123 and SEQ ID NO: 125, or SEQ ID NO: 133 and SEQ ID NO: 135, or SEQ ID NO:. 143 and SEQ ID NO: 145, or SEQ ID NO: 153 and SEQ ID NO: 155, or SEQ ID NO: 163 and SEQ ID NO: 165, or SEQ ID NO: 173 and SEQ ID NO: 175, or SEQ ID NO: 183 and SEQ ID NO: 185, or SEQ ID NO: 193 and SEQ ID NO: 195, or SEQ ID NO: 203 and SEQ ID NO: 205, or SEQ ID NO: 213 and SEQ ID NO: 215, or SEQ ID NO: 223 and SEQ ID NO: 225, or SEQ ID NO: 233 and SEQ ID NO: 235, or SEQ ID NO: 243 and SEQ ID NO: 245, or SEQ ID NO: 253 and SEQ ID NO: 255, or SEQ ID NO: 263 and SEQ ID NO: 265, or SEQ ID NO: 273 and SEQ ID NO: 275, or SEQ ID NO: 283 and SEQ ID NO: 285 or a sequence having at least 75% sequence identity to any one of the forgoing sequences.

25. A vector comprising a nucleic acid sequence according to any one of claims 23 to 24.

26. A host cell comprising the nucleic acid sequence according to any one of claims 23 to 24 or a vector of claim 25.

27. A kit comprising an antibody or antigen-binding portion thereof according to any one of claims 1 to 15 or a pharmaceutical composition according to claim 16.

28. The kit according to claim 27 further comprising a reagent for the detection of the antibody or antigen-binding portion thereof.

29. A method for making a canine antibody that binds PD-1 comprising culturing the isolated host cell of claim 26 and recovering said antibody.

30. A method for making a canine antibody that binds PD-1 comprising the steps of a) immunising a transgenic mouse that expresses a nucleic acid construct comprising canine heavy chain V genes and canine light chain V genes with PD-1 antigen, b) generating a library of antibodies from said mouse and c) isolating an antibody from said library.31 . A method for detecting a PD-1 protein or an extracellular domain of a PD-1 protein in a biological sample from a canine subject, comprising contacting a biological sample with the antibody or antigenbinding portion thereof of any one of claims 1 to 15 wherein said antibody or antigen-binding portion thereof is linked to a detectable label.

32. The method of claim 31 , wherein the biological sample is a biopsy, tissue, blood, serum, plasma, or lymphatic fluid sample.

33. A method of inhibiting tumor growth or metastasis comprising contacting a tumor cell with an effective amount of the antibody or antigen-binding portion thereof according to any one of claims 1 to 15 or pharmaceutical composition according to claim 16.

34. A method of killing a tumor cell expressing PD-1 , comprising contacting the cell with the antibody of any one of claims 1 to 15 or pharmaceutical composition according to claim 16, such that killing of the cell expressing PD-1 occurs.

35. The method of claim 34 wherein the tumor cell is a canine tumor cell.

36. A binding agent comprising the antibody or antigen-binding portion thereof according to any one of claims 1 to 15 wherein said antibody or antigen-binding portion thereof is linked to a second antibody or antigen-binding portion thereof that binds to a second target.

37. The binding agent according to claim 36 wherein the second target binding agent is selected from any one of the list comprising LAG-3, 0X40, OX40L, CD2, CD27, CDS, ICAM-1 , LFA-1 (CD11 a / CD18), ICOS (CD278), 4-1 BB (CD137), GITR, CD30, CD40, BAFFR, HVEM, CD7, LIGHT, NKG2C, SLAMF7, NKp80, CD160, B7-H3 or CD83 ligand, CD3, CD8, CD28, CD4 or ICAM-1.

38. An immunoconjugate comprising the antibody or antigen-binding portion thereof according to any one of claims 1 to 15 or the binding agent of claim 36 or 37.

39. A method of modulating an immune response comprising administering an antibody or fragment thereof according to any one of claims 1 to 15, or a pharmaceutical composition according to claim 16 or a binding agent according to any one of claims 36 to 37, or an immunoconjugate according to any one of claims 38 to 39.

40. A combination therapy comprising an antibody or fragment thereof according to any one of claims 1 to 15, or a pharmaceutical composition according to claim 16 or a binding agent according to any one of claims 36 to 37, or an immunoconjugate according to any one of claims 38 to 39 and a further therapeutic moiety.

41. A combination therapy according to claim 40 wherein the further therapeutic moiety is an antibody optionally an antibody that binds an immunooncology target, or a chemotherapy agent.