Canine anti-CD20 antibodies
The invention provides canine CD20 specific antibodies, methods of making the antibodies and methods of use of the antibodies.
1. An isolated antibody or antigen-binding portion thereof that specifically binds canine CD20, wherein the antibody comprises:
(i) a VH CDR1 of SEQ ID NO:9, a VH CDR2 of SEQ ID NO:10, VH CDR3 of SEQ ID NO:11, a VL CDR1 of SEQ ID NO:21, a VL CDR2 of SEQ ID NO:22, and a VL CDR3 of SEQ ID NO:23;
(ii) a VH CDR1 of SEQ ID NO:12, a VH CDR2 of SEQ ID NO:13, VH CDR3 of SEQ ID NO:14, a VL CDR1 of SEQ ID NO:24, a VL CDR2 of SEQ ID NO:25, and a VL CDR3 of SEQ ID NO:26;
(iii) a VH CDR1 of SEQ ID NO:15, a VH CDR2 of SEQ ID NO:16, VH CDR3 of SEQ ID NO:17, a VL CDR1 of SEQ ID NO:27, a VL CDR2 of SEQ ID NO:28, and a VL CDR3 of SEQ ID NO:29; or
(iv) a VH CDR1 of SEQ ID NO:18, a VH CDR2 of SEQ ID NO:19, VH CDR3 of SEQ ID NO:20, a VL CDR1 of SEQ ID NO:30, a VL CDR2 of SEQ ID NO:31, and a VL CDR3 of SEQ ID NO:32.
2. The isolated antibody or antigen-binding portion thereof of claim 1 , wherein the antibody or antigen-binding portion thereof is a monoclonal antibody, a polyclonal antibody, a chimeric antibody, a humanized antibody, a synthetic antibody, a single chain antibody, a diabody, a caninized antibody, a canine antibody, a human antibody, or a CDR-grafted antibody.
3. The isolated antibody or antigen-binding portion thereof of claim 1 , wherein (i) the antibody or antigen-binding portion thereof comprising a VH CDR1 of SEQ ID NO:9, a VH CDR2 of SEQ ID NO:10, VH CDR3 of SEQ ID NO:11, comprises a VL amino acid sequence of SEQ ID NO:5;
(ii) the antibody or antigen-binding portion thereof comprising a VH CDR1 of SEQ ID NO:12, a VH CDR2 of SEQ ID NO:13, VH CDR3 of SEQ ID NO:14, comprises a VL amino acid sequence of SEQ ID NO:6;
(iii) the antibody or antigen-binding portion thereof comprising a VH CDR1 of SEQ ID NO:15, a VH CDR2 of SEQ ID NO:16, VH CDR3 of SEQ ID NO:17, comprises a VL amino acid sequence of SEQ ID NO:7;
(iv) the antibody or antigen-binding portion thereof comprising a VH CDR1 of SEQ ID NO:18, a VH CDR2 of SEQ ID NO:19, VH CDR3 of SEQ ID NO:20, comprises a VL amino acid sequence of SEQ ID NO:8.
4. The isolated antibody or antigen-binding portion thereof of claim 1 , wherein said (i) antibody or antigen-binding portion thereof comprising a VL CDR1 of SEQ ID NO:21, a VL CDR2 of SEQ ID NO:22, and a VL CDR3 of SEQ ID NO:23 comprises a VH amino acid sequence of SEQ ID NO:1;
(ii) antibody or antigen-binding portion thereof comprising a VL CDR1 of SEQ ID NO:24, a VL CDR2 of SEQ ID NO:25, and a VL CDR3 of SEQ ID NO:26 comprises a VH amino acid sequence of SEQ ID NO:2;
(iii) antibody or antigen-binding portion thereof comprising a VL CDR1 of SEQ ID NO:27, a VL CDR2 of SEQ ID NO:28, and a VL CDR3 of SEQ ID NO:29 comprises a VH amino acid sequence of SEQ ID NO:3;
(iv) antibody or antigen-binding portion thereof comprising a VL CDR1 of SEQ ID NO:30, a VL CDR2 of SEQ ID NO:31, and a VL CDR3 of SEQ ID NO:32 comprises a VH amino acid sequence of SEQ ID NO:4.
5. A composition comprising the antibody or antigen-binding portion thereof of claim 1 and a pharmaceutically acceptable carrier.
6. The isolated antibody or antigen-binding portion thereof of claim 1 , wherein the antibody or antigen-binding portion thereof is an IgG1, an IgG2, an IgG2 a , an IgG2 b , an IgG3, or an IgG4.
7. The isolated antibody or antigen-binding portion thereof of claim 1 , wherein the antibody or antigen-binding portion thereof specifically binds canine CD20 with an affinity (K d ) of at least about 10 −6 M.
8. The isolated antibody or antigen-binding portion thereof of claim 1 , wherein said antibody or antigen-binding portion thereof induces apoptosis of CD20+cells.
9. The isolated antibody or antigen-binding portion thereof of claim 1 , wherein the antibody or antigen-binding portion thereof comprises the same heavy and light chain polypeptide sequences as an antibody produced by hybridoma ATCC number PTA-9433 (4F1), ATCC number PTA-9434 (6C8), ATCC number PTA -9435 (14A12), or ATCC number PTA-9436 (18D3).
10. The antibody or antigen-binding portion thereof of claim 1 , wherein the antibody is produced by the hybridoma cell line having ATCC number PTA-9433 (4F1), ATCC number PTA-9434 (6C8), ATCC number PTA-9435 (14A12), or ATCC number PTA-9436 (18D3).
11. An isolated cell of hybridoma ATCC number PTA-9433 (4F1), ATCC number PTA-9434 (6C8), ATCC number PTA-9435 (14A12), or ATCC number PTA-9436 (18D3).
12. The isolated antibody or antigen-binding portion thereof of claim 1 , wherein said antibody or antigen-binding portion thereof specifically binds to the surface of canine lymphocytes.