Bispecific HER2 antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-10584178-B2
Application number	US-201615186098-A
Country	US
Kind code	B2
Filing date	Jun 17, 2016
Priority date	Dec 20, 2013
Publication date	Mar 10, 2020
Grant date	Mar 10, 2020

Abstract

The present invention relates to bispecific HER2 antibodies, novel HER2 antibody variants, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

First claim

We claim:

1. A bispecific antibody comprising a first antigen binding site specific for extracellular domain II of HER2 and a second antigen binding site specific for extracellular domain IV of HER2, wherein the antibody comprises
(a) a first heavy chain comprising a heavy chain CDR1 of SEQ ID NO: 55, a heavy chain CDR 2 of SEQ ID NO: 77, and a heavy chain CDR 3 of SEQ ID NO: 56;
(b) a second heavy chain comprising a heavy chain CDR1 of SEQ ID NO: 20, a heavy chain CDR2 of SEQ ID NO: 29, and a heavy chain CDR3 of SEQ ID NO: 30;
(c) a first light chain comprising a light chain CDR1 of SEQ ID NO: 89; a light chain CDR2 of SEQ ID NO: 90; and a light chain CDR3 of SEQ ID NO: 19; and
(d) a second light chain comprising a light chain CDR1 of SEQ ID NO: 89; a light chain CDR2 of SEQ ID NO: 90; and a light chain CDR3 of SEQ ID NO: 19.

2. A bispecific antibody comprising a first antigen binding site specific for extracellular domain II of HER2 and a second antigen binding site specific for extracellular domain IV of HER2, wherein the antibody comprises two variable light chains comprising the amino acid sequence of SEQ ID NO: 54, a first heavy chain comprising a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 64, and a second heavy chain comprising a variable heavy chain comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 92.

3. The bispecific antibody of claim 1 or 2 , wherein said antibody induces complement-dependent cytotoxicity to a higher degree than the combination of Pertuzumab and Trastuzumab.

4. The bispecific antibody of claim 3 , wherein the complement dependent cytotoxicity of the bispecific antibody is determined by a LDH assay or a complement assay and compared to the complement dependent cytotoxicity of the combination of Pertuzumab and Trastuzumab as determined by the same assay.

5. The bispecific antibody of claim 4 , wherein the complement dependent cytotoxicity is determined in vitro on cancer cells, preferably on breast cancer cells.

6. A pharmaceutical composition comprising a bispecific antibody of claim 1 or claim 2 .

Assignees

• Hoffmann La Roche

Inventors

• Croasdale-Wood Rebecca
• Hanisch Lydia Jasmin
• Georges Guy
• Hofer Thomas
• Hosse Ralf
• Klein Christian
• Moessner Ekkehard
• Moser Samuel
• Schaefer Wolfgang
• Schanzer Juergen Michael
• Scheuer Werner
• Sustmann Claudio
• Umana Pablo

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title