Heterodimeric antibody Fc-containing proteins and methods for production thereof

Patent metadata

Field	Value
Publication number	US-10597464-B2
Application number	US-201715414122-A
Country	US
Kind code	B2
Filing date	Jan 24, 2017
Priority date	Apr 20, 2010
Publication date	Mar 24, 2020
Grant date	Mar 24, 2020

Abstract

Novel heterodimeric antibody-Fc-containing proteins, such as bispecific antibodies, and novel methods for producing such proteins.

First claim

The invention claimed is:

1. A heterodimeric antibody obtained or obtainable by a method comprising the following steps:
a) providing a first nucleic-acid construct encoding a first chimeric, humanized, or human heavy chain comprising a first Fc region, said first Fc region comprising a first CH3 region of human IgG1, but with an amino acid substitution at position 405 (numbering according to the EU Index),
b) providing a second nucleic-acid construct encoding a second chimeric, humanized, or human heavy chain comprising a second Fc region, said second Fc region comprising a first CH3 region of human IgG1, but with an amino acid substitution at position 409 (numbering according to the EU Index),
wherein the heterodimeric antibody does not bind to c-Met and/or EGFR,
c) co-expressing said first and second nucleic-acid constructs in a host cell, and
d) obtaining said heterodimeric antibody from the cell culture.

2. The heterodimeric antibody of claim 1 , wherein said first and second heavy chains are full-length heavy chains of two antibodies that bind different epitopes.

3. The heterodimeric antibody of claim 2 , further comprising two full-length light chains.

4. A pharmaceutical composition comprising a heterodimeric antibody according to claim 1 and a pharmaceutically-acceptable carrier.

5. The heterodimeric antibody of claim 1 , wherein step c) further comprises co-expressing one or more nucleic-acid constructs encoding a light-chain in said host cell.

6. The heterodimeric antibody of claim 1 , wherein said first Fc region comprises an Arg at position 409 and said second Fc region comprises a Leu at position 405.

7. A heterodimeric antibody comprising a first chimeric, humanized, or human heavy chain comprising a first Fc region, said first Fc region comprising a first CH3 region of human IgG1, but with an amino acid substitution at position 405 (numbering according to the EU Index), and a second chimeric, humanized, or human heavy chain comprising a second Fc region, said second Fc region comprising a second CH3 region of human IgG1, but with an amino acid substitution at position 409 (numbering according to the EU Index), wherein the sequences of the first and second CH3 regions are different, and wherein the heterodimeric antibody does not bind to c-Met and/or EGFR.

8. A pharmaceutical composition comprising a heterodimeric antibody according to claim 7 and a pharmaceutically-acceptable carrier.

9. The heterodimeric antibody of claim 7 , wherein said first and second heavy chains bind different epitopes.

10. The heterodimeric antibody of claim 7 , wherein said first Fc region comprises an Arg at position 409, and said second Fc region comprises a Leu at position 405.

11. The heterodimeric antibody of claim 7 , wherein neither said first nor said second heavy chain comprises a Cys-Pro-Ser-Cys (SEQ ID NO: 5) sequence in the hinge region.

12. The heterodimeric antibody of claim 7 , wherein both said first and said second heavy chains comprise a Cys-Pro-Pro-Cys (SEQ ID NO: 4) sequence in the hinge region.

Assignees

• Genmab As

Inventors

• Labrijn Aran Frank
• Meesters Joyce I
• Van Den Bremer Ewald T J
• Neijssen Joost J
• Van Berkel Patrick
• De Goeij Bart
• Vink Tom
• Van De Winkel Jan
• Schuurman Janine
• Parren Paul

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• G01N33/6854

  Immunoglobulins · CPC title

• C07K16/46 Primary

  Hybrid immunoglobulins (hybrids of an immunoglobulin with a peptide not being an immunoglobulin C07K19/00) · CPC title

• C07K16/2809

  against the T-cell receptor (TcR)-CD3 complex · CPC title

• C07K2317/24

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