Anti-HER2 antibodies and immunoconjugates

Patent metadata

Field	Value
Publication number	US-12492263-B2
Application number	US-202217720717-A
Country	US
Kind code	B2
Filing date	Apr 14, 2022
Priority date	Sep 12, 2014
Publication date	Dec 9, 2025
Grant date	Dec 9, 2025

Abstract

The invention provides anti-HER2 antibodies and immunoconjugates and methods of using the same.

First claim

What is claimed is:

1 . An isolated antibody that binds to HER2, wherein the antibody comprises
(i)(a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 15; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 20 or 21; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 17; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 12; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 13; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 14; (ii)(a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 15; (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO: 8; (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO: 22; (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 12; (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO: 13; and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO: 14; (iii) a light chain variable region comprising the sequence of SEQ ID NO: 10 and a heavy chain variable region comprising the sequence of SEQ ID NO: 11 with one of the following substitutions: (a) position 53 is serine, position 55 is serine, and position 101 is lysine; (b) position 53 is methionine and position 55 is serine; or (c) position 53 is leucine, wherein positions are numbered according to Kabat numbering; or (iv) a light chain variable region comprising the sequence of SEQ ID NO: 10 and a heavy chain variable region comprising the sequence of SEQ ID NO: 11 with one of the following substitutions (a) HVR-H2 (SEQ ID NO: 16) is substituted with SEQ ID NO: 8 and HVR-H3 (SEQ ID NO: 17) is substituted with SEQ ID NO: 22; (b) HVR-H2 (SEQ ID NO: 16) is substituted with SEQ ID NO: 20; or (c) HVR-H2 (SEQ ID NO: 16) is substituted with SEQ ID NO: 21.

2 . The antibody of claim 1 , wherein the antibody comprises
(i) a light chain variable region comprising the sequence of SEQ ID NO: 10 and a heavy chain variable region comprising the sequence of SEQ ID NO: 11 with one of the following substitutions (a) position 53 is serine, position 55 is serine, and position 101 is lysine; (b); (b) position 53 is methionine and position 55 is serine; or (c) position 53 is leucine, wherein positions are numbered according to Kabat numbering; or (ii) a light chain variable region comprising the sequence of SEQ ID NO: 10 and a heavy chain variable region comprising the sequence of SEQ ID NO: 11 with one of the following substitutions (a) HVR-H2 (SEQ ID NO: 16) is substituted with SEQ ID NO: 8 and HVR-H3 (SEQ ID NO: 17) is substituted with SEQ ID NO: 22; (b) HVR-H2 (SEQ ID NO: 16) is substituted with SEQ ID NO: 20; or (c) HVR-H2 (SEQ ID NO: 16) is substituted with SEQ ID NO: 21.

3 . The antibody of claim 1 , which is a monoclonal, humanized, or chimeric antibody.

4 . The antibody of claim 1 , which is an antibody fragment that binds HER2.

5 . The antibody of claim 1 , wherein the antibody binds to extracellular domain I of HER2.

6 . The antibody of claim 1 , which is an IgG1, IgG2a or IgG2b antibody.

7 . The antibody of claim 1 , wherein the antibody comprises at least one mutation in the heavy chain constant region selected from A118C and S400C.

8 . The antibody of claim 1 , wherein the antibody comprises at least one mutation in the light chain constant region selected from K149C and V205C.

9 . The antibody of claim 1 , wherein the antibody comprises the heavy chain constant region of SEQ ID NO: 28 or SEQ ID NO: 19.

10 . The antibody of claim 1 , wherein the antibody comprises the light chain constant region of SEQ ID NO: 25 or SEQ ID NO: 23.

11 . An isolated nucleic acid encoding the antibody of claim 1 .

12 . A host cell comprising the nucleic acid of claim 11 .

13 . A method of producing an antibody comprising culturing the host cell of claim 12 so that the antibody is produced.

14 . An immunoconjugate comprising the antibody of claim 1 and a cytotoxic agent.

15 . The antibody of claim 1 , conjugated to a label.

Assignees

• Genentech Inc

Inventors

• Chen Xiaocheng
• Dennis Mark
• Junutula Jagath Reddy
• Phillips Gail Lewis
• Pillow Thomas Harden
• Sliwkowski Mark X

Classifications

• G01N33/57515

  of the breast · CPC title

• G01N33/5759

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

• G01N33/5753

  of the stomach or small intestine · CPC title

• C07K16/3015

  Breast · CPC title

• A61K49/00

  Preparations for testing in vivo · CPC title