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 has an amino acid sequence:
GFNIKDTYMH,
(SEQ ID NO: 121)
V H CDR#2 has an amino acid sequence:
RIDPANGNTKYDPKFQG,
(SEQ ID NO: 122)
V H CDR#3 has an amino acid sequence:
GGPAWFVY,
(SEQ ID NO: 123)
V L CDR#1 has an amino acid sequence:
RASQDISNYLN,
(SEQ ID NO: 114)
V L CDR#2 has an amino acid sequence:
YTSRLRS,
(SEQ ID NO: 125)
and
V L CDR#3 has an amino acid sequence:
QQGNTLPWT.
(SEQ ID NO: 126)
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: 26)
EVQLVQSGAEVKKPGSSVKVSCKASGFNIKDTYMHWVRQAPGQGLEWIGR
IDPANGNTKYDPKFQGRATITADTSTNTAYMELSSLRSEDTAVYYCARGG
PAWFVYWGQGTLVTVSS;
and a V L chain having an amino acid sequence according to:
(SEQ ID NO: 36)
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYY
TSRLRSGLPSRFSGSGSGTDYTLTISSLQPEDFATYYCQQGNTLPWTFGG
GTKVEIK.
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 SEQ ID NOS: 45 or 46; and a light chain having an amino acid sequence according to SEQ ID NO:53.
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-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 has an amino acid sequence:
GFNIKDTYMH,
(SEQ ID NO: 121)
V H CDR#2 has an amino acid sequence:
RIDPANGNTKYDPKFQG,
(SEQ ID NO: 122)
V H CDR#3 has an amino acid sequence:
GGPAWFVY,
(SEQ ID NO: 123)
V L CDR#1 has an amino acid sequence:
RASQDISNYLN,
(SEQ ID NO: 114)
V L CDR#2 has an amino acid sequence:
YTSRLRS,
(SEQ ID NO: 125)
and
V L CDR#3 has an amino acid sequence:
QQGNTLPWT.
(SEQ ID NO: 126)
11. A vector comprising the nucleic acid of claim 10 .
12. A prokaryotic host cell transformed with the vector of claim 11 .
13. A eukaryotic host cell transformed with the vector of claim 11 .
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.