Anti-IL-13 receptor alpha 2 antibodies and antibody-drug conjugates
Disclosed herein are anti-IL-13-Rα2 antibodies and antibody drug conjugates and methods for preparing and using the same.
1. An isolated antibody or antigen-binding fragment thereof that specifically binds to human IL-13 receptor alpha 2 (IL-13-Rα2) wherein the antibody comprises a heavy chain variable region and a light chain variable region comprising
a heavy chain variable region comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 1 and a light chain variable region comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 5.
2. An antibody-drug conjugate comprising a cytotoxic agent conjugated to the antibody or antigen-binding fragment thereof of claim 1 .
3. A nucleic acid that encodes the antibody or antigen-binding fragment thereof of claim 1 .
4. A vector comprising the nucleic acid of claim 3 .
5. An isolated host cell comprising the vector of claim 4 .
6. A process for producing an antibody comprising cultivating the isolated host cell of claim 5 and recovering the antibody from a cell culture.
7. An isolated antibody or antigen-binding fragment thereof that specifically binds to human IL-13-Rα2, wherein the antibody comprises:
a heavy chain CDR1 comprising SEQ ID NO: 2;
a heavy chain CDR2 comprising SEQ ID NO: 3;
a heavy chain CDR3 comprising SEQ ID NO: 4;
a light chain CDR1 comprising SEQ ID NO: 6;
a light chain CDR2 comprising SEQ ID NO: 7 and
a light chain CDR3 comprising SEQ ID NO: 8.
8. The isolated antibody or antigen-binding fragment thereof of claim 7 , wherein said isolated antibody comprises the heavy chain variable region set forth in the amino acid sequence SEQ ID NO: 1.
9. The isolated antibody or antigen-binding fragment thereof of claim 7 , wherein said isolated antibody comprises the light chain variable region set forth in the amino acid sequence SEQ ID NO: 5.
10. The isolated antibody or antigen-binding fragment thereof of claim 7 , wherein said antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 50.
11. The isolated antibody or antigen-binding fragment thereof of claim 1 , wherein said antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 51.
12. An antibody-drug conjugate of the formula:
Ab-(L-D)
wherein:
(a) Ab is an isolated antibody or antigen-binding fragment thereof that specifically binds to human IL-13-Rα2 wherein the antibody comprises a heavy chain variable region and a light chain variable region comprising a heavy chain variable region comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 1 and a light chain variable region comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 5; and
(b) L-D is a linker-drug moiety, wherein L is a linker, and D is a drug.
13. The antibody-drug conjugate of claim 12 wherein L is selected from the group consisting of Maleimidocaproyl-Val-Cit-PABA (vc), maleimidocaproyl (mc), and maleimide-propylene glycol (MalPeg).
14. The antibody-drug conjugate of claim 12 wherein D is selected from the group consisting of 0101, 3377, 0131, 6121, 3906, 6780 and 8261.
15. The antibody-drug conjugate of claim 12 wherein L-D is selected from the group consisting of vc-0101 and mc-3377.
16. The antibody-drug conjugate of claim 12 , wherein Ab comprises a heavy chain variable region and a light chain variable region comprising
a heavy chain variable region comprising a CDR1, CDR2, and CDR3 of SEQ ID NO: 1 and a light chain variable region comprising a CDR1, CDR2, and CDR3 of sequence of SEQ ID NO: 5.
17. The antibody-drug conjugate of claim 12 , wherein Ab comprises a heavy chain variable region and a light chain variable region comprising:
a heavy chain CDR1 comprising SEQ ID NO: 2;
a heavy chain CDR2 comprising SEQ ID NO: 3;
a heavy chain CDR3 comprising SEQ ID NO: 4;
a light chain CDR1 comprising SEQ ID NO: 6;
a light chain CDR2 comprising SEQ ID NO: 7 and
a light chain CDR3 comprising SEQ ID NO: 8.
18. An antibody-drug conjugate of the formula:
Ab-(L-D)
wherein:
(a) Ab is an isolated antibody or antigen-binding fragment thereof of claim 1 ; and
(b) L-D is a linker-drug moiety of vc-0101.
19. An antibody-drug conjugate of the formula:
Ab-(L-D)
wherein:
(a) Ab is an isolated antibody or antigen-binding fragment thereof of claim 1 ; and
(b) L-D is a linker-drug moiety of mc-3377.
20. A pharmaceutical composition comprising the antibody-drug conjugate of claim 12 and a pharmaceutically acceptable carrier.
21. A method of treating an IL-13-Rα2 expressing cancer in to patient in need thereof comprising administering to said patient the antibody-drug conjugate of claim 12 .
22. The method of claim 21 wherein said cancer is selected from the group consisting of lung, colon, stomach, pancreatic, ovarian, malignant gliomas, and melanoma.
23. A process for producing an anti-IL-13-Rα2 antibody-drug conjugate of claim 12 comprising:
(a) linking a linker selected from the group consisting of vc, mc and MalPeg to the drug;
(b) conjugating said linker-drug moiety to the antibody; and,
(c) purifying the antibody-drug conjugate.