Heterodimeric antibodies that bind CD3 and tumor antigens

Patent metadata

Field	Value
Publication number	US-11111315-B2
Application number	US-201815945681-A
Country	US
Kind code	B2
Filing date	Apr 4, 2018
Priority date	Nov 26, 2014
Publication date	Sep 7, 2021
Grant date	Sep 7, 2021

Abstract

The present invention is directed to novel heterodimeric antibodies.

First claim

What is claimed:

1. A composition comprising an CD123 antigen binding domain comprising:
a) a variable heavy domain comprising a vhCDR1 having SEQ ID NO:440, vhCDR2 having SEQ ID NO:441 and a vhCDR3 having SEQ ID NO:442; and
b) a variable light domain comprising a v1CDR1 having SEQ ID NO:444, v1CDR2 having SEQ ID NO:445 and a v1CDR3 having SEQ ID NO:446.

2. A composition according to claim 1 , wherein said variable heavy domain has an amino acid sequence according to SEQ ID NO:439 and said variable light domain has an amino acid sequence according to SEQ ID NO:443.

3. A heterodimeric antibody comprising:
a) a first monomer comprising:
i) a first IgG Fc domain; and
ii) a single chain variable fragment comprising a first variable heavy chain, a first variable light chain, and a linker that attaches said first variable heavy chain with said first variable light chain;

b) a second monomer comprising:
i) a VH-CH1-hinge-CH2-CH3 monomer, wherein VH is a second variable heavy chain comprising a vhCDR1 having SEQ ID NO:440, vhCDR2 having SEQ ID NO:441 and a vhCDR3 having SEQ ID NO:442, and CH2-CH3 is a second IgG Fc domain; and

c) a light chain comprising a second variable light chain comprising a v1CDR1 having SEQ ID NO:444, v1CDR2 having SEQ ID NO:445 and a v1CDR3 having SEQ ID NO:446,
wherein said second variable heavy chain and said second variable light chain form a CD123 binding domain.

4. A heterodimeric antibody according to claim 3 , wherein said second variable heavy chain has an amino acid sequence having SEQ ID NO: 439 and said second variable light chain has an amino acid sequence having SEQ ID NO: 443.

5. A nucleic acid composition comprising:
a) a nucleic acid encoding the variable heavy domain of claim 1 ; and
b) a nucleic acid encoding the variable light domain of claim 1 .

6. An expression vector composition comprising:
a) a first expression vector comprising a first nucleic acid encoding said variable heavy domain of claim 1 ; and
b) a second expression vector comprising a second nucleic acid encoding said variable light domain of claim 1 .

7. A host cell comprising said expression vector composition of claim 6 .

8. A nucleic acid composition comprising:
a) a first nucleic acid encoding said first monomer of claim 3 ;
b) a second nucleic acid encoding said second monomer chain of claim 3 ; and
c) a third nucleic acid encoding said light chain of claim 3 .

9. An expression vector composition comprising:
a) a first expression vector comprising a first nucleic acid encoding said first monomer of claim 3 ;
b) a second expression vector comprising a second nucleic acid encoding said second monomer chain of claim 3 ; and
c) a third expression vector comprising a third nucleic acid encoding said light chain of claim 3 .

10. A host cell comprising said expression vector composition of claim 9 .

11. A method of making a heterodimeric antibody according to claim 3 comprising culturing the host cell according to claim 10 under conditions wherein said heterodimeric antibody is expressed, and recovering said heterodimeric antibody.

Assignees

• Xencor Inc

Inventors

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

Classifications

• C07K2317/92

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

• C07K16/2887

  against CD20 · CPC title

• C07K16/2809

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

• C07K2317/526

  CH3 domain · CPC title

• C07K16/468 Primary

  Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies · CPC title