Anti-OX40 antibodies and their uses
The present disclosure provides novel anti-OX40 antibodies, compositions including the antibodies, nucleic acids encoding the antibodies, and methods of making and using the same.
1. An anti-OX40 antibody which comprises (i) a V H chain comprising three CDRs; and (ii) a V L chain comprising three CDRs, wherein:
V H CDR#1 is selected from:
(SEQ ID NO: 111)
GYSIASGYYWN,
(SEQ ID NO: 121)
GFNIKDTYMH,
(SEQ ID NO: 131)
GFSLTSYGVH;
V H CDR#2 is selected from:
(SEQ ID NO: 112)
YISYDGSNNYNPSLG,
(SEQ ID NO: 122)
RIDPANGNTKYDPKFQG,
(SEQ ID NO: 132)
VIWSGGSTDYNAAFIS;
V H CDR#3 is selected from:
(SEQ ID NO: 113)
TLPYYFDY,
(SEQ ID NO: 123)
GGPAWFVY,
(SEQ ID NO: 133)
EEFDY;
V L CDR#1 is selected from:
(SEQ ID NO: 114)
RASQDISNYLN;
V L CDR#2 is selected from:
(SEQ ID NO: 115)
YTSRLHS,
(SEQ ID NO: 125)
YTSRLRS;
and V L CDR#3 is selected from:
(SEQ ID NO: 116)
QQGNTLPLT,
(SEQ ID NO: 126)
QQGNTLPWT,
(SEQ ID NO: 136)
QQGYTLPPT.
2. The anti-OX40 antibody of claim 1 , which is monoclonal.
3. The anti-OX40 antibody of claim 1 , which is humanized.
4. The anti-OX40 antibody of claim 3 , which comprises a V H chain having an amino acid sequence according to:
(SEQ ID NO: 24)
EVQLQESGPGLVKPSDTLSLTCAVSGYSIASGYYWNWIRQPPGKGLEWM
GYISYDGSNNYNPSLGNRITISRDTSKNQVSLKLSSVTAVDTAVYYCVK
TLPYYFDYWGQGTTVTVSS;
(SEQ ID NO: 26)
EVQLVQSGAEVKKPGSSVKVSCKASGFNIKDTYMHWVRQAPGQGLEWIG
RIDPANGNTKYDPKFQGRATITADTSTNTAYMELSSLRSEDTAVYYCAR
GGPAWFVYWGQGTLVTVSS; or
(SEQ ID NO: 28)
EVQLVESGGGLVQPGGSLRLSCAVSGFSLTSYGVHWVRQAPGKGLEWLG
VIWSGGSTDYNAAFISRLTISKDNSKSTVYLQMNSLRAEDTAVYYCARE
EFDYWGQGTTVTVSS;
and a V L chain having an amino acid sequence according to:
(SEQ ID NO: 34)
DIQMTQTPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIF
YTSRLHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQGNTLPLTF
GQGTKLEIK;
(SEQ ID NO: 36)
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIY
YTSRLRSGLPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQGNTLPWTF
GGGTKVEIK; or
(SEQ ID NO: 38)
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWFQQKPGKAPKLLIY
YTSRLHSGVPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQGYTLPPTF
GGGTKVEIK.
5. The anti-OX40 antibody of claim 3 , which is an IgG.
6. The anti-OX40 antibody of claim 5 , which is an IgG 1 .
7. The anti-OX40 antibody of claim 3 comprising a kappa light chain constant region.
8. The anti-OX40 antibody of claim 1 which comprises a heavy chain having an amino acid sequence according to any one of SEQ ID NOS:43-48 ;and a light chain having an amino acid sequence according to any one of SEQ ID NOS:52-54.
9. A pharmaceutical composition comprising the anti-OX40 antibody of claim 1 , and a pharmaceutically acceptable carrier.
10. A nucleic acid comprising a nucleotide sequence encoding an anti-OX40antibody which comprises (i) a V H chain comprising three CDRs; and (ii) a V L chain comprising three CDRs, wherein:
(SEQ ID NO: 111)
V H CDR#1 is selected from:
GYSIASGYYWN,
(SEQ ID NO: 121)
GFNIKDTYMH,
(SEQ ID NO: 131)
GFSLTSYGVH;
(SEQ ID NO: 112)
V H CDR#2 is selected from:
YISYDGSNNYNPSLG,
(SEQ ID NO: 122)
RIDPANGNTKYDPKFQG,
(SEQ ID NO: 132)
VIWSGGSTDYNAAFIS;
(SEQ ID NO: 113)
V H CDR#3 is selected from:
TLPYYFDY,
(SEQ ID NO: 123)
GGPAWFVY,
(SEQ ID NO: 133)
EEFDY;
(SEQ ID NO: 114)
V L CDR#1 is selected from:
RASQDISNYLN;
(SEQ ID NO: 115)
V L CDR#2 is selected from:
YTSRLHS,
(SEQ ID NO: 125)
YTSRLRS;
(SEQ ID NO: 116)
and V L CDR#3 is selected from:
QQGNTLPLT,
(SEQ ID NO: 126)
QQGNTLPWT,
(SEQ ID NO: 136)
QQGYTLPPT.
11. A vector comprising the nucleic acid of claim 10 .
12. A prokaryotic host cell transformed with the vector of claim 10 .
13. A eukaryotic host cell transformed with the vector of claim 10 .
14. The eukaryotic host cell of claim 13 which is a mammalian host cell.
15. A method of producing an anti-OX40 antibody, comprising: (a) culturing the host cell of claim 14 and (b) recovering the anti-OX40 antibody.
16. A method of treating a cancer, comprising administering to a patient in need thereof an effective amount of an anti-OX40 antibody which comprises (i) a V H chain comprising three CDRs; and (ii) a V L chain comprising three CDRs, wherein:
(SEQ ID NO: 111)
V H CDR#1 is selected from:
GYSIASGYYWN,
(SEQ ID NO: 121)
GFNIKDTYMH,
(SEQ ID NO: 131)
GFSLTSYGVH;
(SEQ ID NO: 112)
V H CDR#2 is selected from:
YISYDGSNNYNPSLG,
(SEQ ID NO: 122)
RIDPANGNTKYDPKFQG,
(SEQ ID NO: 132)
VIWSGGSTDYNAAFIS;
(SEQ ID NO: 113)
V H CDR#3 is selected from:
TLPYYFDY,
(SEQ ID NO: 123)
GGPAWFVY,
(SEQ ID NO: 133)
EEFDY;
(SEQ ID NO: 114)
V L CDR#1 is selected from:
RASQDISNYLN;
(SEQ ID NO: 115)
V L CDR#2 is selected from:
YTSRLHS,
(SEQ ID NO: 125)
YTSRLRS;
(SEQ ID NO: 116)
and V L CDR#3 is selected from:
QQGNTLPLT,
(SEQ ID NO: 126)
QQGNTLPWT,
(SEQ ID NO: 136)
QQGYTLPPT.
17. The method of claim 16 , wherein the cancer is selected from bladder cancer, breast cancer, head and neck cancer, gastric cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, skin cancer, and a tumor with evidence of DNA mismatch repair deficiency.
18. The method of claim 17 , wherein the lung cancer is small cell lung cancer, non-small cell lung cancer, or mesothelioma.