Heterodimeric antibodies that bind CD3 and tumor antigens

Patent metadata

Field	Value
Publication number	US-11225528-B2
Application number	US-201916354058-A
Country	US
Kind code	B2
Filing date	Mar 14, 2019
Priority date	Nov 26, 2014
Publication date	Jan 18, 2022
Grant date	Jan 18, 2022

Abstract

The present invention is directed to novel heterodimeric antibodies.

First claim

What is claimed is:

1. A heterodimeric antibody comprising:
a) a first monomer comprising, from N- to C-terminus, a VH1-CH1-linker 1-VL2-scFv linker-VH2-linker 2-CH2-CH3,
wherein VL2-scFv linker-VH2 is an anti-CD3 scFv, linker 1 and linker 2 are a first linker and second linker, respectively, and CH2-CH3 is a first IgG Fc domain;
b) a second monomer comprising, from N- to C-terminus, a VH1-CH1-hinge-CH2-CH3, wherein VH1 is a first variable heavy domain and CH2-CH3 is a second IgG Fc domain;
c) a common light chain (VL1) comprising a first variable light domain (VL1); and
wherein the first variable heavy domain (VH1) on the first monomer and the first variable light domain (VL1) form a first binding domain, and the first variable heavy domain (VH1) on the second monomer and the first variable light domain (VL1) form a second binding domain, and
wherein the second variable heavy domain (VH2) and second variable light domain (VL2) have the amino acid sequence SEQ ID NO: 10 and SEQ ID NO: 14, or SEQ ID NO: 19 and SEQ ID NO: 23, respectively.

2. The heterodimeric antibody of claim 1 , wherein VH2 has the amino acid sequence of SEQ ID NO: 10, and VL2 has the amino acid sequence of SEQ ID NO: 14.

3. The heterodimeric antibody of claim 1 , wherein VH2 has the amino acid sequence of SEQ ID NO: 19, and VL2 has the amino acid sequence of SEQ ID NO: 23.

4. A heterodimeric antibody according to claim 1 , wherein the first and second IgG Fc domains are variants of a human IgG Fc domain.

5. A heterodimeric antibody according to claim 1 , wherein the first IgG Fc domain comprises amino acid substitutions S364K/E357Q and the second IgG Fc domain comprises amino acid substitutions L368D/K370S, wherein numbering is according to EU numbering.

6. A heterodimeric antibody according to claim 1 , wherein the CH1-hinge-CH2-CH3 of the second monomer comprises amino acid substitutions N208D/Q295E/N384D/Q418E/N421D, wherein numbering is according to EU numbering.

7. A heterodimeric antibody according to claim 1 , wherein the first and second IgG Fc domains comprise amino acid substitutions E233P/L234V/L235A/G236del/S267K, wherein numbering is according to EU numbering.

8. A heterodimeric antibody according to claim 1 , wherein the scFv linker is a charged linker.

9. A heterodimeric antibody according to claim 1 , wherein the first IgG Fc domain comprises amino acid substitutions S364K/E357Q and the second Fc domain comprises amino acid substitutions L368D/K370S,
wherein the first and second IgG Fc domains each comprise amino acid substitutions E233P/L234V/L235A/G236del/S267K, and
wherein the CH1-hinge-CH2-CH3 of the second monomer comprises amino acid substitutions N208D/Q295E/N384D/Q418E/N421D, wherein numbering is according to EU numbering.

10. A polynucleotide composition comprising:
a) a first polynucleotide encoding the first monomer of claim 1 ;
b) a second polynucleotide encoding the second monomer of claim 1 ; and
c) a third polynucleotide encoding the common light chain of claim 1 .

11. An expression vector composition comprising:
a) a first expression vector comprising a first polynucleotide encoding the first monomer of claim 1 ;
b) a second expression vector comprising a second polynucleotide encoding the second monomer of claim 1 ; and
c) a third expression vector comprising a third polynucleotide encoding the common light chain of claim 1 .

12. A host cell comprising the expression vector composition of claim claim 11 .

13. A method of making a heterodimeric antibody comprising culturing the host cell of claim 12 under conditions wherein the heterodimeric antibody is expressed, and recovering the heterodimeric antibody.

Assignees

• Xencor Inc

Inventors

• Bernett Matthew J
• Moore Gregory
• Desjarlais John
• Chu Seung
• Rashid Rumana
• Muchhal Umesh
• Lee Sung-Hyung

Classifications

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/528

  CH4 domain · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• C07K16/3061

  Blood cells · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title