Anti-B7-H4 antibodies and immunoconjugates

Patent metadata

Field	Value
Publication number	US-12134649-B2
Application number	US-202117547528-A
Country	US
Kind code	B2
Filing date	Dec 10, 2021
Priority date	Mar 14, 2013
Publication date	Nov 5, 2024
Grant date	Nov 5, 2024

Abstract

The invention provides anti-B7-H4 antibodies and immunoconjugates and methods of using the same.

First claim

What is claimed is:

1. An isolated antibody that binds to B7-H4, wherein the antibody comprises:
(a)(i) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 13, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 14, and (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 15.

2. The antibody of claim 1 , further comprising:
(a)(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 16, (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 17, and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 18.

3. An isolated antibody that binds to B7-H4, wherein the antibody comprises:
(a)(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 16, (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 17, and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 18.

4. The antibody of claim 2 , wherein the antibody comprises:
(a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 12; or
(b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 11; or
(c) a VH sequence as in (a) and a VL sequence as in (b).

5. The antibody of claim 4 , comprising a VH sequence of SEQ ID NO: 12 and/or a VL sequence of SEQ ID NO: 11.

6. The antibody of claim 5 , comprising a VH sequence of SEQ ID NO: 12 and a VL sequence of SEQ ID NO: 11.

7. The antibody of claim 2 , which is an IgG1, IgG2a or IgG2b antibody.

8. Isolated nucleic acid encoding the antibody of claim 2 .

9. A host cell comprising the nucleic acid of claim 8 .

10. A method of producing an antibody comprising culturing the host cell of claim 9 so that the antibody is produced.

11. An immunoconjugate comprising the antibody of claim 2 and a cytotoxic agent.

12. The immunoconjugate of claim 11 having the formula Ab-(L-D)p, wherein:
(a) Ab is the antibody;
(b) L is a linker;
(c) D is a cytotoxic agent selected from a maytansinoid, an auristatin, a calicheamicin, a pyrrolobenzodiazepine, and a nemorubicin derivative; and
(d) p ranges from 1-8.

13. A pharmaceutical formulation comprising the immunoconjugate of claim 11 and a pharmaceutically acceptable carrier.

14. The pharmaceutical formulation of claim 13 , further comprising an additional therapeutic agent.

15. A method of treating an individual having a B7-H4-positive cancer, the method comprising administering to the individual an effective amount of the immunoconjugate of claim 11 .

16. A method of inhibiting proliferation of an B7-H4-positive cell, the method comprising exposing the cell to the immunoconjugate of claim 11 under conditions permissive for binding of the immunoconjugate to B7-H4 on the surface of the cell, thereby inhibiting proliferation of the cell.

17. A method of detecting human B7-H4 in a biological sample comprising contacting the biological sample with the anti-B7-H4 antibody of claim 2 under conditions permissive for binding of the anti-B7-H4 antibody to a naturally occurring human B7-H4, and detecting whether a complex is formed between the anti-B7-H4 antibody and a naturally occurring human B7-H4 in the biological sample.

18. A method for detecting an B7-H4-positive cancer comprising:
(i) administering a labeled anti-B7-H4 antibody to a subject having or suspected of having a B7-H4-positive cancer, wherein the labeled anti-B7-H4 antibody comprises the anti-B7-H4 antibody of claim 2 , and
(ii) detecting the labeled anti-B7-H4 antibody in the subject, wherein detection of the labeled anti-B7-H4 antibody indicates a B7-H4-positive cancer in the subject.

19. The antibody of claim 2 , which is a monoclonal antibody.

20. The antibody of claim 19 , which is a humanized or chimeric antibody.

Assignees

• Genentech Inc

Inventors

• Leong Steven R
• Polson Andrew
• Polakis Paul
• Wu Yan
• Liang Wei-Ching
• Firestein Ron

Classifications

• G01N33/56972

  White blood cells · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title

• C07K16/3015

  Breast · CPC title

• A61K51/1051

  the tumor cell being from breast, e.g. the antibody being herceptin · CPC title