Heterodimeric proteins

• US 9,605,084 B2
• Filed: 03/07/2014
• Issued: 03/28/2017
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Xencor, Inc.
• Original Assignee: Xencor, Inc.
• Inventors: Moore, Gregory, Rashid, Rumana, Desjarlais, John
• Primary Examiner(s): Gamett, Daniel C
• Application Number:
  US14/200,821
• Publication Number:
  US 20140294823A1
• Time in Patent Office: 1,117 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 16/468 Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/72 Increased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

The present invention describes novel immunoglobulin compositions that co-engage at least two antigens, e.g. a first and second antigen, or, as outlined herein, three or four antigens can be bound, in some of the scaffold formats described herein. First and second antigens of the invention are herein referred to as antigen-1 and antigen-2 respectively (or antigen-3 and antigen-4, if applicable. As outlined herein, a number of different formats can be used, with some scaffolds relying combinations of monovalent and bivalent bindings.

Claims

1. A composition comprising a heterodimeric protein comprising a heterodimeric Fc domain comprising:

a) a first monomer comprising a first variant Fc domain comprising amino acid substitutions L368E and K370S; and

b) a second monomer comprising a second variant Fc domain comprising amino acid substitution S364K,

wherein numbering is according to the EU index as in Kabat, and wherein said first and second variant Fc domains are variant human IgG Fc domains.

2. A composition according to claim 1 wherein said first and second monomers each comprise a CH1-hinge-CH2-CH3 monomer.

3. A composition according to claim 1, wherein said first and second variant Fc domains are selected from the group consisting of variant IgG1, IgG2 and IgG4 Fc domains.

4. A nucleic acid encoding a first monomer according to claim 1.

5. A nucleic acid encoding a second monomer according to claim 1.

6. A host cell comprising a first nucleic acid encoding a first monomer according to claim 1 and a second nucleic acid encoding a second monomer according to claim 1.

7. A method of making a composition according to claim 1 comprising culturing a host cell according to claim 6.

8. A composition comprising a heterodimeric protein comprising a heterodimeric Fc domain comprising:

a) a first monomer comprising a first Fc domain comprising amino acid substitutions L368E and K370S; and

b) a second monomer comprising a second variant Fc domain comprising amino acid substitution S364K,

wherein numbering is according to the EU index as in Kabat, and wherein said first and second variant Fc domains are variant human IgG Fc domains.

9. A composition according to claim 8 wherein said first monomer comprises a third fusion partner.

10. A composition according to claim 8 wherein said second monomer comprises a fourth fusion partner.

11. A composition according to claim 8, wherein said first and second monomers each comprise a CH1-hinge-CH2-CH3 monomer.

12. A composition according to claim 8, wherein said first and second variant Fc domains are selected from the group consisting of variant IgG1, IgG2 and IgG4 Fc domains.

13. A nucleic acid encoding a first monomer according to claim 8.

14. A nucleic acid encoding a second monomer according to claim 8.

15. A host cell comprising a first nucleic acid encoding a first monomer according to claim 8 and a second nucleic acid encoding a second monomer according to claim 8.

16. A method of making a composition according to claim 8 comprising culturing a host cell according to claim 14.