Heterodimeric proteins

Patent metadata

Field	Value
Publication number	US-9650446-B2
Application number	US-201414205248-A
Country	US
Kind code	B2
Filing date	Mar 11, 2014
Priority date	Jan 14, 2013
Publication date	May 16, 2017
Grant date	May 16, 2017

Abstract

The invention provides novel heterodimeric proteins including heterodimeric antibodies.

First claim

We claim:

1. A heterodimeric antibody comprising:
a) a first heavy chain 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 chain, a variable light chain and a charged scFv linker, wherein said charged scFv linker covalently attaches said first variable heavy chain and said variable light chain; and
b) a second heavy chain comprising a VH-CH1-hinge-CH2-CH3 monomer, wherein VH is a second variable heavy chain and CH2-CH3 is a second variant Fc domain; and
c) a light chain;
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
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 the charged linker is a positive charged linker.

3. The heterodimeric antibody of claim 1 , wherein the charged linker has the amino acid sequence SEQ ID NO: 450.

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 2 , wherein said first and second variant Fc domains are selected from the group consisting of variant human IgG1, IgG2 and IgG4 variant Fc domains.

6. The heterodimeric antibody of claim 3 , wherein said first and second variant Fc domains are selected from the group consisting of variant human IgG1, IgG2 and IgG4 variant Fc domains.

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

8. The heterodimeric antibody of claim 2 wherein said first and second variant Fc domains are variant human IgG1 Fc domains.

9. The heterodimeric antibody of claim 3 wherein said first and second variant Fc domains are variant human IgG1 Fc domains.

Assignees

• Xencor Inc

Inventors

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

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07K2317/55

  Fab or Fab' · CPC title

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title