Optimized anti-CD20 monoclonal antibodies having Fc variants

• US 8,084,582 B2
• Filed: 06/30/2005
• Issued: 12/27/2011
• Est. Priority Date: 03/03/2003
• Status: Active Grant

• Current Assignee: Xencor, Inc.
• Original Assignee: Xencor, Inc.
• Inventors: Dahiyat, Bassil I., Lazar, Gregory Alan, Vafa, Omid
• Primary Examiner(s): DAHLE, CHUN WU
• Application Number:
  US11/174,287
• Publication Number:
  US 20060121032A1
• Time in Patent Office: 2,371 Days
• Field of Search: None
• US Class Current: 530/387.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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 16/2893 against CD52
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• 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 2317/77 Internalization into the cell
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The present invention relates to optimized CD20 antibodies having Fc variants, methods for their generation, and method for their application, such as methods of enhancing macrophage activation, particularly for therapeutic purposes.

Claims

1. A protein comprising a human Fc variant of a parent human Fc polypeptide, wherein said Fc variant comprises an amino acid modification in the Fc region of said parent Fc polypeptide at position 328, wherein numbering is according to the EU index.

2. A protein according to claim 1 wherein said amino acid modification is selected from the group consisting of 328A, 328D, 328E, 328F, 328G, 328H, 328I, 328K, 328M, 328N, 328P, 328Q, 328R, 328S, 328T, 328V, 328W and 328Y.

3. A protein according to claim 1 wherein said amino acid modification is 328R.

4. A protein according to claim 1 wherein said amino acid modification is 328F.

5. A protein according to claim 1 wherein said amino acid modification is 328Y.

6. A protein according to claim 1, wherein said human Fc variant exhibits altered binding to an Fcγ

R as compared to the parent Fc polypeptide.

7. A protein according to claim 1, wherein said protein is an antibody.

8. A protein according to claim 7, wherein said antibody is a human antibody.