Anti-B7-H4 antibodies and immunoconjugates

Patent metadata

Field	Value
Publication number	US-11230600-B2
Application number	US-201816167000-A
Country	US
Kind code	B2
Filing date	Oct 22, 2018
Priority date	Mar 14, 2013
Publication date	Jan 25, 2022
Grant date	Jan 25, 2022

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) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 21, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 22, and (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 23.

2. The antibody of claim 1 , further comprising:
(a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 24, (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 25, and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 26.

3. An isolated antibody that binds to B7-H4, wherein the antibody comprises:
(a) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 24, (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 25, and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 26.

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: 20; or
(b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 19; or
(c) a VH sequence as in (a) and a VL sequence as in (b).

5. The antibody of claim 4 , comprising:
(a) a VH sequence of SEQ ID NO: 20; and/or
(b) a VL sequence of SEQ ID NO: 19.

6. The antibody of claim 5 , comprising: (a) a VH sequence of SEQ ID NO: 20 and a VL sequence of SEQ ID NO: 19.

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 1 , wherein the antibody has at least one of the following characteristics:
(a) binds to an epitope within all or a portion of the B7-H4 Ig-V containing domain (amino acids 29-157 of SEQ ID NO: 73); or binds to an epitope within all or a portion of the B7-H4 Ig-C containing domain (amino acids 158-250 of SEQ ID NO: 73); or binds to an epitope within all or a portion of the B7-H4 Ig-V and Ig-C domains (amino acids 29-250 of SEQ ID NO:73); or binds to an epitope within all or a portion of SEQ ID NO: 74 (mature human B7-H4); or binds to an epitope within all or a portion of SEQ ID NO: 73 (precursor human B7-H4), and
(b) binds to B7-H4 with an affinity of ≤50 nM.

20. The antibody of claim 2 , wherein the antibody has at least one of the following characteristics:
(a) binds to an epitope within all or a portion of the B7-H4 Ig-V containing domain (amino acids 29-157 of SEQ ID NO: 73); or binds to an epitope within all or a portion of the B7-H4 Ig-C containing domain (amino acids 158-250 of SEQ ID NO: 73); or binds to an epitope within all or a portion of the B7-H4 Ig-V and Ig-C domains (amino acids 29-250 of SEQ ID NO:73); or binds to an epitope within all or a portion of SEQ ID NO: 74 (mature human B7-H4); or binds to an epitope within all or a portion of SEQ ID NO: 73 (precursor human B7-H4), and
(b) binds to B7-H4 with an affinity of <50 nM.

21. The antibody of claim 3 , wherein the antibody has at least one of the following characteristics:
(a) binds to an epitope within all or a portion of the B7-H4 Ig-V containing domain (amino acids 29-157 of SEQ ID NO: 73); or binds to an epitope within all or a portion of the B7-H4 Ig-C containing domain (amino acids 158-250 of SEQ ID NO: 73); or binds to an epitope within all or a portion of the B7-H4 Ig-V and Ig-C domains (amino acids 29-250 of SEQ ID NO:73); or binds to an epitope within all or a portion of SEQ ID NO: 74 (mature human B7-H4); or binds to an epitope within all or a portion of SEQ ID NO: 73 (precursor human B7-H4), and
(b) binds to B7-H4 with an affinity of ≤50 nM.

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

23. The antibody of claim 22 , 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

• A61K51/1027

  against receptors, cell-surface antigens or cell-surface determinants · CPC title

• A61K47/6809

  Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin · CPC title

• A61K47/65

  Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers · CPC title

• A61K47/6801

  Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent · CPC title

• A61K38/08

  Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title