Anti-B7-H4 antibodies and immunoconjugates

Patent metadata

Field	Value
Publication number	US-12281165-B2
Application number	US-202217677283-A
Country	US
Kind code	B2
Filing date	Feb 22, 2022
Priority date	Sep 12, 2014
Publication date	Apr 22, 2025
Grant date	Apr 22, 2025

Abstract

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

First claim

What is claimed is:

1. Isolated nucleic acid encoding
an antibody that binds to B7-H4, wherein the antibody comprises:
(a) (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 39, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 40, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 128, (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 42, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 43, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 129; or
(b) (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 39, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 40, and (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 41, (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 42, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 43, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 129.

2. A host cell comprising the nucleic acid of claim 1 .

3. A method of producing an antibody comprising culturing the host cell of claim 1 so that the antibody is produced.

4. The method of claim 3 , further comprising isolating the antibody.

5. The isolated nucleic acid of claim 1 , wherein the antibody further comprises a heavy chain framework FR3 sequence of SEQ ID NO: 53.

6. The isolated nucleic acid of claim 1 , wherein the antibody comprises a light chain framework FR3 sequence of SEQ ID NO: 47.

7. The isolated nucleic acid of claim 1 , wherein the antibody comprises:
(a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 38;
(b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 126; or
(c) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 127; or
(d) a VH sequence as in (a) and a VL sequence as in (b); or
(e) a VH sequence as in (c) and a VL sequence as in (b).

8. The isolated nucleic acid of claim 1 , wherein the antibody comprises a VH sequence of SEQ ID NO: 38 or 127.

9. The isolated nucleic acid of claim 1 , wherein the antibody comprises a VL sequence of SEQ ID NO: 126.

10. The isolated nucleic acid of claim 1 , wherein the antibody comprises: (a) a VH sequence of SEQ ID NO: 38 and a VL sequence of SEQ ID NO: 126; or (b) a VH sequence of SEQ ID NO: 127 and a VL sequence of SEQ ID NO: 126.

11. The isolated nucleic acid of claim 1 , wherein the antibody is a humanized or chimeric antibody.

12. The isolated nucleic acid of claim 1 , wherein the antibody is an antibody fragment that binds B7-H4.

13. The isolated nucleic acid of claim 1 , wherein the antibody is an IgG1, IgG2a or IgG2b antibody.

14. The isolated nucleic acid of claim 1 , wherein the antibody comprises one or more engineered cysteine amino acids residues.

15. The isolated nucleic acid of claim 14 , wherein the one or more engineered cysteine amino acid residues is located in the light chain.

16. The isolated nucleic acid of claim 15 , wherein the antibody comprises at least one mutation in the light chain constant region selected from K149C and V205C.

17. The isolated nucleic acid of claim 14 , wherein the one or more engineered cysteine amino acid residues is located in the heavy chain.

18. The isolated nucleic acid of claim 17 , wherein the antibody comprises at least one mutation in the heavy chain constant region selected from A118C and S400C.

19. The isolated nucleic acid of claim 1 , wherein the antibody comprises (a) a heavy chain sequence of SEQ ID NO: 132 and a light chain sequence of SEQ ID NO: 134; or (b) a heavy chain sequence of SEQ ID NO: 130 and a light chain sequence of SEQ ID NO: 140; or (c) a heavy chain sequence of SEQ ID NO: 130 and a light chain sequence of SEQ ID NO: 141; or (d) a heavy chain sequence of SEQ ID NO: 130 and a light chain sequence of SEQ ID NO: 145; or (e) a heavy chain sequence of SEQ ID NO: 130 and a light chain sequence of SEQ ID NO: 146.

20. The isolated nucleic acid of claim 1 , wherein is the antibody binds human B7-H4 of SEQ ID NO: 73.

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

• C07K2317/567

  Framework region [FR] · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• A61K38/05

  Dipeptides · CPC title

• A61K31/706

  containing six-membered rings with nitrogen as a ring hetero atom · CPC title