Optimized FC variants

• US 8,188,231 B2
• Filed: 05/05/2005
• Issued: 05/29/2012
• Est. Priority Date: 09/27/2002
• Status: Active Grant

• Current Assignee: Xencor, Inc.
• Original Assignee: Xencor, Inc.
• Inventors: Lazar, Gregory Alan, Dang, Wei, Desjarlais, John R., Karki, Sher Bahadur, Vafa, Omid, Hayes, Robert, Vielmetter, Jost
• Primary Examiner(s): Dahle, Chun
• Application Number:
  US11/124,620
• Publication Number:
  US 20060024298A1
• Time in Patent Office: 2,581 Days
• Field of Search: None
• US Class Current: 530/387.1
• CPC Class Codes: C07K 16/2893 against CD52
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The present invention relates to optimized Fc variants, methods for their generation, Fc polypeptides comprising optimized Fc variants, and methods for using optimized Fc variants.

Claims

1. A protein comprising an Fc variant of a parent Fc polypeptide, wherein said Fc variant comprises an amino acid modification in the Fc region of said parent Fc polypeptide at position 243, wherein said protein exhibits altered binding affinity to an Fcγ

receptor (Fcγ

R) as compared to a parent polypeptide, wherein numbering is according to the EU index.

3. A protein according to claim 1, wherein said Fcγ

R is Fcγ

RIII.

4. A protein according to claim 1 or 2, wherein said Fc region comprises an engineered glycoform.

5. A protein according to claim 4, wherein said engineered glycoform has a reduced level of fucose as compared to said parent polypeptide.

8. A protein according to claim 1, 2, or 6, wherein said protein is an antibody.

9. A composition comprising a protein according to claim 1, 2, or 6, further comprising an acceptable carrier.

2. A protein comprising an Fc variant of a parent Fc polypeptide, wherein said Fc variant comprises an amino acid modification in the Fc region of said parent Fc polypeptide at position 243, wherein numbering is according to the EU index.

6. A protein comprising an Fc variant of a parent Fc polypeptide, wherein said Fc variant comprises an amino acid modification in the Fc region of said parent Fc polypeptide selected from the group consisting of 243E, 243H, 243L, 243Q, 243R, 243W and 243Y, wherein numbering is according to the EU index.

7. A protein according to claim 6 wherein said amino acid substitution is 243L.

10. An antibody or immunoadhesin, wherein said antibody or immunoadhesin comprises an amino acid modification in the Fc region selected from the group consisting of 243E, 243H, 243L, 243Q, 243R, 243W and 243Y, wherein numbering is according to the EU index.