Anti-B7-H4 antibodies and immunoconjugates

Patent metadata

Field	Value
Publication number	US-9562099-B2
Application number	US-201414207878-A
Country	US
Kind code	B2
Filing date	Mar 13, 2014
Priority date	Mar 14, 2013
Publication date	Feb 7, 2017
Grant date	Feb 7, 2017

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 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) and binds to B7-H4 with an affinity of ≦50 nM, wherein the antibody comprises:
(a)(i) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 31, (ii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 34, and (iii) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 30; or
(b)(i) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 60, (ii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 63, and (iii) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 59.

2. An isolated antibody that binds to B7-H4, wherein the antibody 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) and binds to B7-H4 with an affinity of ≦50 nM, wherein the antibody comprises:
(a)(i) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 29, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 30, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 31; or
(b)(i) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 58, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 59, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 60.

3. An isolated antibody that binds to B7-H4, comprising (a) a VH sequence of SEQ ID NO: 28 and a VL sequence of SEQ ID NO: 27; or (b) a VH sequence of SEQ ID NO: 56 and a VL sequence of SEQ ID NO: 55; or (c) a VH sequence of SEQ ID NO: 56 and a VL sequence of SEQ ID NO: 57.

4. An isolated antibody that binds to B7-H4, wherein the antibody 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) and binds to B7-H4 with an affinity of ≦50 nM, wherein the antibody comprises:
(a)(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 32, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 33, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 34; or
(b)(i) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 61, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 62, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 63.

5. The antibody of claim 4 , further comprising a light chain framework FR2 sequence of SEQ ID NO: 65 or 66 or a light chain framework FR3 sequence of SEQ ID NO: 67.

6. 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: 29, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 30, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 31; (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 32, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 33, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 34; or
(b)(i) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 58, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 59, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 60; (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 61, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 62, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 63.

7. The antibody of claim 6 , which is a monoclonal antibody.

8. The antibody of claim 6 , which is a human, humanized, or chimeric antibody.

9. The antibody of claim 6 , which is an antibody fragment that binds B7-H4.

10. The antibody of claim 6 , wherein B7-H4 is human B7-H4 of SEQ ID NO: 73.

11. The antibody of claim 6 , wherein the antibody comprises:
(a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 28; or
(b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 27; or
(c) a VH sequence as in (a) and a VL sequence as in (b); or
(d) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 56; or
(e) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 55; or
(f) a VH sequence as in (d) and a VL sequence as in (e); or
(g) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 57; or
(h) a VH sequence as in (d) and a VL sequence as in (g).

12. The antibody of claim 11 , comprising a VH sequence of SEQ ID NO: 4 or a VH sequence of SEQ ID NO: 56.

13. The antibody of claim 11 , comprising a VL sequence of SEQ ID NO: 27, a VL sequence of SEQ ID NO: 55, or a VL sequence of SEQ ID NO: 57.

14. The antibody of claim 6 , which is an IgG1, IgG2a or IgG2b antibody.

15. The antibody claim 6 conjugated to a label.

16. The antibody of claim 15 , wherein the label is a positron emitter.

17. The antibody of claim 16 , wherein the positron emitter is 89 Zr.

Assignees

• Genentech Inc

Inventors

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

Classifications

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• C07K16/2827 Primary

  against B7 molecules, e.g. CD80, CD86 · CPC title

• C07K2317/567

  Framework region [FR] · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title