IP Library › Granted Patent US 12,435,143
Granted Patent B2
US 12,435,143 · App. 17/626,239 · Granted Oct 7, 2025

Caninized antibodies against canine CTLA-4

Inventors: Mohamad Morsey (Omaha, NE); Yuanzheng Zhang (Somerset, NJ); Ian Tarpey (St. Ives, GB)
Assignee: INTERVET INC.
C07K16/2818A61K2039/505A61P31/00A61P35/00C07K2317/24C07K2317/565C07K2317/71C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 12,435,143
App. No.
17/626,239
Granted
Oct 7, 2025
Kind
B2
Abstract

The present invention provides caninized murine antibodies against canine CTLA-4 that have specific sequences and a high binding affinity for canine CTLA-4. The present invention further provides epitopes of canine CTLA-4 for caninized murine antibodies against canine CTLA-4.5 The invention also relates to use of these antibodies in the treatment of cancer in canines and other companion animals.

Claims (52)

1. An isolated mammalian antibody or an antigen binding fragment thereof that binds canine Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA-4) and blocks the binding of canine CTLA-4 with canine CD80, blocks the binding of canine CTLA-4 with canine CD86, or blocks both the binding of canine CTLA-4 with canine CD80 and the binding of canine CTLA-4 with canine CD86;

wherein said antibody or antigen binding fragment thereof comprises:

(a) a light chain variable region (VL) complementarity-determining region (CDR)-1 comprising the amino acid sequence of SEQ ID NO: 92;

(b) a VLCDR-2 comprising the amino acid sequence of SEQ ID NO: 94;

(c) a VLCDR-3 comprising the amino acid sequence of SEQ ID NO: 96;

(d) a heavy chain variable region (VH) CDR-1 comprising the amino acid sequence of SEQ ID NO: 86;

(e) a VHCDR-2 comprising the amino acid sequence of SEQ ID NO: 88; and

(f) a VHCDR-3 comprising the amino acid sequence of SEQ ID NO: 90.

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 1 , wherein the antibody or antigen binding fragment thereof is a caninized antibody or a caninized antigen binding fragment.

4. The isolated mammalian antibody or antigen binding fragment thereof of claim 3 , further comprising a hinge region that comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, and SEQ ID NO: 131.

5. The isolated mammalian antibody or antigen binding fragment thereof of claim 3 , comprising a VH; wherein the VH comprises an amino acid sequence of a VH of a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 66, SEQ ID NO:74, SEQ ID NO:76, and SEQ ID NO: 78.

6. The isolated mammalian antibody or antigen binding fragment thereof of claim 5 , wherein the heavy chain is encoded by a nucleotide acid sequence selected from the group consisting of SEQ ID NO: 61, SEQ ID NO: 63, SEQ ID NO: 65, SEQ ID NO: 73, SEQ ID NO: 75, and SEQ ID NO: 77.

7. The isolated mammalian antibody or antigen binding fragment thereof of claim 3 , wherein the antibody or antigen binding fragment thereof binds to any one or more amino acid sequences selected from the group consisting of SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, and SEQ ID NO: 137.

8. A pharmaceutical composition comprising the isolated mammalian caninized antibody or antigen binding fragment thereof of claim 3 , and a pharmaceutically acceptable carrier or diluent.

9. The isolated mammalian antibody or antigen binding fragment thereof of claim 3 , comprising a VL; wherein the VL comprises an amino acid sequence of a VL of a light chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO:50, SEQ ID NO:52, and SEQ ID NO:54.

10. The isolated mammalian antibody or antigen binding fragment thereof of claim 9 , wherein the light chain is encoded by a nucleotide sequence selected from the group consisting of SEQ ID NO:49, SEQ ID NO:51, and SEQ ID NO:53.

11. The isolated mammalian antibody or antigen binding fragment thereof of claim 3 , comprising a VH and a VL; wherein the VH comprises an amino acid sequence of a VH of a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:74, SEQ ID NO: 76, and SEQ ID NO: 78; and wherein the VL comprises an amino acid sequence of a VL of a light chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO:50, SEQ ID NO: 52, and SEQ ID NO:54.

12. The isolated mammalian antibody or antigen binding fragment thereof of claim 11 , wherein the heavy chain encoded by a nucleotide sequence selected from the group consisting of SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:73, SEQ ID NO:75, and SEQ ID NO:77; and wherein the light chain is encoded by a nucleotide sequence selected from the group consisting of SEQ ID NO:49, SEQ ID NO:51, and SEQ ID NO:53.

13. The isolated mammalian antibody or antigen binding fragment thereof of claim 3 , comprising a VH and a VL; wherein the VH comprises an amino acid sequence of a VH of a heavy chain comprising an amino acid sequence set forth in SEQ ID NO:64 or SEQ ID NO: 76; and wherein the VL comprises an amino acid sequence of a VL of a light chain comprising the amino acid sequence set forth in SEQ ID NO: 54.

14. The isolated mammalian antibody or antigen binding fragment thereof of claim 3 , comprising a VH and a VL; wherein the VH comprises an amino acid sequence of a VH of a heavy chain comprising an amino acid sequence set forth in SEQ ID NO:66 or SEQ ID NO: 78; and wherein the VL comprises an amino acid sequence of a VL of a light chain comprising the amino acid sequence set forth in SEQ ID NO: 54.

15. The isolated mammalian antibody or antigen binding fragment thereof of claim 3 , comprising a VH and a VL; wherein

(a) the VH comprises an amino acid sequence of a VH of a heavy chain comprising an amino acid sequence set forth in SEQ ID NO:64 or SEQ ID NO:76; and wherein the VL comprises an amino acid sequence of a VL of a light chain comprising the amino acid sequence set forth in SEQ ID NO:50;

(b) the VH comprises an amino acid sequence of a VH of a heavy chain comprising an amino acid sequence set forth in SEQ ID NO:62 or SEQ ID NO:74; and wherein the VL comprises an amino acid sequence of a VL of a light chain comprising the amino acid sequence set forth in SEQ ID NO:50;

(c) the VH comprises an amino acid sequence of a VH of a heavy chain comprising an amino acid sequence set forth in SEQ ID NO:66 or SEQ ID NO:78; and wherein the VL comprises an amino acid sequence of a VL of a light chain comprising the amino acid sequence set forth in SEQ ID NO:50;

(d) the VH comprises an amino acid sequence of a VH of a heavy chain an amino acid sequence set forth in SEQ ID NO:62 or SEQ ID NO:74; and wherein the VL comprises an amino acid sequence of a VL of a light chain comprising the amino acid sequence set forth in SEQ ID NO:54;

(e) the VH comprises an amino acid sequence of a VH of a heavy chain comprising an amino acid sequence set forth in SEQ ID NO:64 or SEQ ID NO:76; and wherein the VL comprises an amino acid sequence of a VL of a light chain comprising the amino acid sequence set forth in SEQ ID NO:52;

(f) the VH comprises an amino acid sequence of a VH of a heavy chain comprising an amino acid sequence set forth in SEQ ID NO:62 or SEQ ID NO:74; and wherein the VL) comprises an amino acid sequence of a VL of a light chain comprising the amino acid sequence set forth in SEQ ID NO:52; or

(g) the VH comprises an amino acid sequence of a VH of a heavy chain comprising an amino acid sequence set forth in SEQ ID NO:66 or SEQ ID NO:78; and wherein the VL comprises an amino acid sequence of a VL of a light chain comprising the amino acid sequence set forth in SEQ ID NO:52.

16. The isolated mammalian antibody or antigen binding fragment thereof of claim 3 , comprising:

(a) a heavy chain that comprises the amino acid sequence of SEQ ID NO:62 or a sequence that is at least about 95% identical to SEQ ID NO:62, and a light chain that comprises the amino acid sequence of SEQ ID NO:50 or a sequence that is at least about 95% identical to SEQ ID NO:50;

(b) a heavy chain that comprises the amino acid sequence of SEQ ID NO:62 or a sequence that is at least about 95% identical to SEQ ID NO:62, and a light chain that comprises the amino acid sequence of SEQ ID NO:52 or a sequence that is at least about 95% identical to SEQ ID NO:52;

(c) a heavy chain that comprises the amino acid sequence of SEQ ID NO:62 or a sequence that is at least about 95% identical to SEQ ID NO:62, and a light chain that comprises the amino acid sequence of SEQ ID NO:54 or a sequence that is at least about 95% identical to SEQ ID NO:54;

(d) a heavy chain that comprises the amino acid sequence of SEQ ID NO:64 or a sequence that is at least about 95% identical to SEQ ID NO:64, and a light chain that comprises the amino acid sequence of SEQ ID NO:50 or a sequence that is at least about 95% identical to SEQ ID NO:50;

(e) a heavy chain that comprises the amino acid sequence of SEQ ID NO:64 or a sequence that is at least about 95% identical to SEQ ID NO:64, and a light chain that comprises the amino acid sequence of SEQ ID NO:52 or a sequence that is at least about 95% identical to SEQ ID NO:52;

(f) a heavy chain that comprises the amino acid sequence of SEQ ID NO:64 or a sequence that is at least about 95% identical to SEQ ID NO:64, and a light chain that comprises the amino acid sequence of SEQ ID NO:54 or a sequence that is at least about 95% identical to SEQ ID NO:54;

(g) a heavy chain that comprises the amino acid sequence of SEQ ID NO:66 or a sequence that is at least about 95% identical to SEQ ID NO:66, and a light chain that comprises the amino acid sequence of SEQ ID NO:50 or a sequence that is at least about 95% identical to SEQ ID NO:50;

(h) a heavy chain that comprises the amino acid sequence of SEQ ID NO:66 or a sequence that is at least about 95% identical to SEQ ID NO:66, and a light chain that comprises the amino acid sequence of SEQ ID NO:52 or a sequence that is at least about 95% identical to SEQ ID NO:52;

(i) a heavy chain that comprises the amino acid sequence of SEQ ID NO:66 or a sequence that is at least about 95% identical to SEQ ID NO:66, and a light chain that comprises the amino acid sequence of SEQ ID NO:54 or a sequence that is at least about 95% identical to SEQ ID NO:54;

(j) a heavy chain that comprises the amino acid sequence of SEQ ID NO:74 or a sequence that is at least about 95% identical to SEQ ID NO:74, and a light chain that comprises the amino acid sequence of SEQ ID NO:50 or a sequence that is at least about 95% identical to SEQ ID NO:50;

(k) a heavy chain that comprises the amino acid sequence of SEQ ID NO:74 or a sequence that is at least about 95% identical to SEQ ID NO:74, and a light chain that comprises the amino acid sequence of SEQ ID NO:52 or a sequence that is at least about 95% identical to SEQ ID NO:52;

(l) a heavy chain that comprises the amino acid sequence of SEQ ID NO:74 or a sequence that is at least about 95% identical to SEQ ID NO:74, and a light chain that comprises the amino acid sequence of SEQ ID NO:54 or a sequence that is at least about 95% identical to SEQ ID NO:54;

(m) a heavy chain that comprises the amino acid sequence of SEQ ID NO:76 or a sequence that is at least about 95% identical to SEQ ID NO:76, and a light chain that comprises the amino acid sequence of SEQ ID NO:50 or a sequence that is at least about 95% identical to SEQ ID NO:50;

(n) a heavy chain that comprises the amino acid sequence of SEQ ID NO:76 or a sequence that is at least about 95% identical to SEQ ID NO:76, and a light chain that comprises the amino acid sequence of SEQ ID NO:52 or a sequence that is at least about 95% identical to SEQ ID NO:52;

(o) a heavy chain that comprises the amino acid sequence of SEQ ID NO:76 or a sequence that is at least about 95% identical to SEQ ID NO:76, and a light chain that comprises the amino acid sequence of SEQ ID NO:54 or a sequence that is at least about 95% identical to SEQ ID NO:54;

(p) a heavy chain that comprises the amino acid sequence of SEQ ID NO:78 or a sequence that is at least about 95% identical to SEQ ID NO:78, and a light chain that comprises the amino acid sequence of SEQ ID NO:50 or a sequence that is at least about 95% identical to SEQ ID NO:50;

(q) a heavy chain that comprises the amino acid sequence of SEQ ID NO:78 or a sequence that is at least about 95% identical to SEQ ID NO:78, and a light chain that comprises the amino acid sequence of SEQ ID NO:52 or a sequence that is at least about 95% identical to SEQ ID NO:52; or

(r) a heavy chain that comprises the amino acid sequence of SEQ ID NO:78 or a sequence that is at least about 95% identical to SEQ ID NO:78, and a light chain that comprises the amino acid sequence of SEQ ID NO:54 or a sequence that is at least about 95% identical to SEQ ID NO:54.

17. The isolated mammalian antibody or antigen binding fragment thereof of claim 3 , comprising a heavy chain that comprises the amino acid sequence of SEQ ID NO:64 and a light chain that comprises the amino acid sequence of SEQ ID NO:54.

18. The isolated mammalian antibody or antigen binding fragment thereof of claim 3 , comprising a heavy chain that comprises the amino acid sequence of SEQ ID NO:76 and a light chain that comprises the amino acid sequence of SEQ ID NO:54.

19. The isolated mammalian antibody or antigen binding fragment thereof of claim 3 , comprising a heavy chain that comprises the amino acid sequence of SEQ ID NO:66 and a light chain that comprises the amino acid sequence of SEQ ID NO:54.

20. The isolated mammalian antibody or antigen binding fragment thereof of claim 3 , comprising a heavy chain that comprises the amino acid sequence of SEQ ID NO:78 and a light chain that comprises the amino acid sequence of SEQ ID NO:54.

Assignments (10)
CHANGE OF ADDRESS Recorded Sep 26, 2023
From: INTERVET INC.
To: INTERVET INC.
Reel/Frame 065028/0818 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 13, 2022
From: MORSEY, MOHAMAD; ZHANG, YUANZHENG
To: INTERVET INC.
Reel/Frame 058647/0014 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 13, 2022
From: TARPEY, IAN
To: INTERVET UK LTD.
Reel/Frame 058646/0951 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 13, 2022
From: INTERVET UK LTD.
To: INTERVET INTERNATIONAL B.V.
Reel/Frame 058647/0163 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 13, 2022
From: INTERVET INTERNATIONAL B.V.
To: INTERVET INC.
Reel/Frame 058647/0299 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 13, 2022
From: MORSEY, MOHAMAD; ZHANG, YUANZHENG; TARPEY, IAN
To: INTERVET INC.
Reel/Frame 058647/0426 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 11, 2022
From: INTERVET UK LTD.
To: INTERVET INTERNATIONAL B.V.
Reel/Frame 058622/0245 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 11, 2022
From: INTERVET INTERNATIONAL B.V.
To: INTERVET INC.
Reel/Frame 058622/0331 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 11, 2022
From: TARPEY, IAN
To: INTERVET UK LTD.
Reel/Frame 058622/0052 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 11, 2022
From: MORSEY, MOHAMAD; ZHANG, YUANZHENG
To: INTERVET INC.
Reel/Frame 058621/0848 →
Continuity (4)
Provisional Application 63048873 · Jul 7, 2020
Provisional Application 62926047 · Oct 25, 2019
Provisional Application 62874287 · Jul 15, 2019
Related Publication 20220251208A1 · Aug 11, 2022
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