Heterodimeric proteins

Patent metadata

Field	Value
Publication number	US-11634506-B2
Application number	US-202016918922-A
Country	US
Kind code	B2
Filing date	Jul 1, 2020
Priority date	Jan 14, 2013
Publication date	Apr 25, 2023
Grant date	Apr 25, 2023

Abstract

The invention provides novel heterodimeric proteins including heterodimeric antibodies.

First claim

We claim:

1. A heterodimeric antibody comprising:
a) a first monomer comprising:
i) a first variant Fc domain; and
ii) a single chain Fv region (scFv) that binds a first antigen, wherein said scFv region comprises a first variable heavy domain, a first variable light domain and a scFv linker, wherein said scFv linker covalently attaches said first variable heavy domain and said first variable light domain; and

b) a second monomer comprising a VH-CH1-hinge-CH2-CH3 monomer, wherein VH is a second variable heavy domain and CH2-CH3 is a second variant Fc domain; and
c) a light chain comprising a second variable light domain (VL) and a constant light chain region;

wherein said VH and VL bind a second antigen, wherein said second variant Fc domain comprises amino acid substitutions N208D/Q295E/N384D/Q418E/N421D, wherein said first and second variant Fc domains each comprise amino acid substitutions E233P/L234V/L235A/G236del/S267K and M428L/N434S; and wherein said first variant Fc domain comprises amino acid substitutions S364K/E357Q and second variant Fc domain comprises amino acid substitutions L368D/K370S, wherein numbering is according to the EU index as in Kabat.

2. The heterodimeric antibody of claim 1 , wherein said scFv linker is a charged linker.

3. The heterodimeric antibody of claim 2 , wherein said charged linker is a positively charged linker.

4. The heterodimeric antibody of claim 1 , wherein said first and second variant Fc domains are selected from the group consisting of variant human IgG1, IgG2 and IgG4 variant Fc domains.

5. The heterodimeric antibody of claim 1 wherein said first and second variant Fc domains are variant human IgG1 Fc domains.

6. A nucleic acid composition comprising:
a) a first nucleic acid encoding said first monomer of claim 1 ;
b) a second nucleic acid encoding said second monomer of claim 1 ; and
c) a third nucleic acid encoding said light chain of claim 1 .

7. An expression vector composition comprising:
a) a first expression vector comprising said first nucleic acid of claim 6 ;
b) a second expression vector comprising said second nucleic acid of claim 6 ; and
c) a third expression vector comprising said third nucleic acid of claim 6 .

8. A host cell comprising the expression vector composition of claim 7 .

9. A method of making a heterodimeric antibody comprising culturing the host cell of claim 8 under conditions wherein said antibody is expressed and recovering said antibody.

Assignees

• Xencor Inc

Inventors

• Moore Gregory
• Bernett Matthew
• Rashid Rumana
• Desjarlais John

Classifications

• C07K2317/64

  comprising a combination of variable region and constant region components · CPC title

• C07K2317/52

  Constant or Fc region; Isotype · CPC title

• C07K2317/528

  CH4 domain · CPC title

• C07K2317/55

  Fab or Fab' · CPC title

• C07K16/468 Primary

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