Modified FC molecules

• US 9,040,041 B2
• Filed: 06/04/2010
• Issued: 05/26/2015
• Est. Priority Date: 10/03/2005
• Status: Active Grant

• Current Assignee: Xencor, Inc.
• Original Assignee: Xencor, Inc.
• Inventors: Desjarlais, John R., Karki, Sher Bahadur, Lazar, Gregory Alan, Richards, John O., Moore, Gregory L., Carmichael, David F.
• Primary Examiner(s): DAHLE, CHUN WU
• Application Number:
  US12/794,560
• Publication Number:
  US 20100249382A1
• Time in Patent Office: 1,817 Days
• Field of Search: None
• US Class Current: 424/130.1
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 16/2863 against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 16/2887 against CD20
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• 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 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/77 Internalization into the cell

Abstract

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

Claims

1. A method of enhancing mediation of ADCP (antibody dependent cellular phagocytosis) comprising contacting a antibody with a macrophage expressing FcyRIIa, wherein said antibody comprises an Fc variant of a human parent Fc polypeptide, wherein said Fc variant comprises an amino acid substitution at position 236 in the Fc region as compared to the human parent Fc polypeptide, wherein said substitution is alanine, said Fc variant is an engineered glycoform with reduced fucose content as compared to the human parent Fc polypeptide, and said Fc variant exhibits an increase in affinity for Fcγ

RIIa over Fcγ

RIIb, thereby resulting in the binding of said Fc variant to FcyRIIa, wherein said increased affinity is relative to the affinity exhibited by the human parent Fc polypeptide and wherein the numbering is according to the EU index.

2. The method of claim 1, wherein said antibody is selected from the group consisting of a human antibody, a humanized antibody, and a monoclonal antibody.

3. The method of claim 1, wherein said antibody has specificity for a target antigen selected from the group consisting of Ep-CAM, CD19, CD20, CD22, CD30, CD33, CD40, CD40L, CD52, Her2/neu, EGFR, IGF-1 R, EpCAM, MUC1, GD3, CEA, CA 125, HLA-DR, MUC18, and prostate specific membrane antigen (PMSA).