Anti-ULBP6 antibodies

Patent metadata

Field	Value
Publication number	US-12060426-B2
Application number	US-202318309272-A
Country	US
Kind code	B2
Filing date	Apr 28, 2023
Priority date	Apr 29, 2022
Publication date	Aug 13, 2024
Grant date	Aug 13, 2024

Abstract

The present disclosure relates to a ULBP6 binding protein that inhibits the interaction between ULBP6 and NKG2D, and methods of treating cancer with said ULBP6 binding protein.

First claim

The invention claimed is:

1. An anti-ULBP6 antibody comprising 6 CDRs selected from the following:
CDRH1 of SEQ ID NO: 36, CDRH2 of SEQ ID NO: 37, CDRH3 of SEQ ID NO: 38, CDRL1 of SEQ ID NO: 51, CDRL2 of SEQ ID NO: 52 and CDRL3 of SEQ ID NO: 53;
CDRH1 of SEQ ID NO: 39, CDRH2 of SEQ ID NO: 40, CDRH3 of SEQ ID NO: 41, CDRL1 of SEQ ID NO: 54, CDRL2 of SEQ ID NO: 55 and CDRL3 of SEQ ID NO: 56;
CDRH1 of SEQ ID NO: 42, CDRH2 of SEQ ID NO: 43, CDRH3 of SEQ ID NO: 44, CDRL1 of SEQ ID NO: 57, CDRL2 of SEQ ID NO: 58 and CDRL3 of SEQ ID NO: 59; or
CDRH1 of SEQ ID NO: 45, CDRH2 of SEQ ID NO: 46, CDRH3 of SEQ ID NO: 47, CDRL1 of SEQ ID NO: 60, CDRL2 of SEQ ID NO: 61 and CDRL3 of SEQ ID NO: 62.

2. The anti-ULBP6 antibody according to claim 1 , wherein the antibody comprises:
a VH region that is at least 80% identical to SEQ ID NO: 21 and a VL region that is at least 80% identical to SEQ ID NO: 31;
a VH region that is at least 80% identical to SEQ ID NO: 22 and a VL region that is at least 80% identical to SEQ ID NO: 32;
a VH region that is at least 80% identical to SEQ ID NO: 23 and a VL region that is at least 80% identical to SEQ ID NO: 33; or
a VH region that is at least 80% identical to SEQ ID NO: 24 and a VL region that is at least 80% identical to SEQ ID NO: 34.

3. The anti-ULBP6 antibody according to claim 1 , wherein the antibody comprises:
a) a Heavy Chain (HC) sequence at least 80% identical to any one of SEQ ID NOs: 75-78, 85-88 or 95-98; and/or
b) a Light Chain (LC) sequence at least 80% identical to any one of SEQ ID NOs: 105-108.

4. The anti-ULBP6 antibody according to claim 1 , wherein the antibody inhibits the interaction of human ULBP6 and human NKG2D.

5. The anti-ULBP6 antibody according to claim 1 , wherein the antibody inhibits the binding of soluble ULBP6 to NKG2D.

6. The anti-ULBP6 antibody according to claim 1 , wherein the antibody comprises a modified Fc region.

7. The anti-ULBP6 antibody according to claim 6 , wherein the modified Fc region comprises the amino acid substitutions S239D and 1332E (as numbered according to the EU index).

8. The anti-ULBP6 antibody according to claim 1 , wherein the antibody is afucosylated.

9. The anti-ULBP6 antibody according to claim 6 , wherein the modified Fc region comprises amino acid substitutions selected from S239D/A330L/1332E, G236A/S239D/A330L/1332E, L235V/F243L/R292P/Y300L/P396L or F243L/R292P/Y300L/V305l/P396L (as numbered according to the EU index).

10. An isolated nucleic acid which encodes an amino acid sequence of the anti-ULBP6 antibody of claim 1 .

11. An expression vector comprising the isolated nucleic acid of claim 10 .

12. A recombinant host cell comprising the isolated nucleic acid of claim 10 .

13. A recombinant host cell comprising the expression vector of claim 11 .

14. A method for the production of an anti-ULBP6 antibody comprising culturing a recombinant host cell of claim 12 under suitable conditions whereby the anti-ULBP6 antibody is produced.

15. A cell line that expresses the anti-ULBP6 antibody of claim 1 .

16. A pharmaceutical composition comprising the anti-ULBP6 antibody of claim 1 and a pharmaceutically acceptable excipient.

17. A method for the treatment of cancer in a subject in need thereof comprising administering to said subject a therapeutically effective amount of the anti-ULBP6 antibody of claim 1 .

Assignees

• 23Andme Inc
• Glaxosmithkline Intellectual Property No 3 Ltd

Inventors

• Benjamin Joel
• Bharill Shashank
• Chen I-Ling
• Chen Yu
• Chung Wei-Jen
• Dizicheh Zahra Bahrami
• Fuh Germaine
• Koenig Patrick
• Liu Yujie
• Poggio Mauro
• Yadav Shruti
• Tsai Ping-Chiao
• Spitzfaden Claus

Classifications

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title