Optimized Fc variants and methods for their generation

• US 9,714,282 B2
• Filed: 05/23/2014
• Issued: 07/25/2017
• Est. Priority Date: 09/26/2003
• Status: Active Grant

• Current Assignee: Xencor, Inc.
• Original Assignee: Xencor, Inc.
• Inventors: Dang, Wei, Chirino, Arthur J., Hayes, Robert J., Vafa, Omid, Doberstein, Stephen K., Lazar, Gregory Alan, Desjarlais, John R., Karki, Sher Bahadur
• Primary Examiner(s): DAHLE, CHUN WU
• Application Number:
  US14/286,825
• Publication Number:
  US 20140377256A1
• Time in Patent Office: 1,159 Days
• Field of Search: None
• 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 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• 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 2317/71 Decreased effector function due to an Fc-modification
• 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 2317/734 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, and antibodies and Fc fusions comprising optimized Fc variants.

Claims

1. A protein comprising an Fc variant of a parent Fc polypeptide, said Fc variant comprising an amino acid substitution A330R in the Fc region, wherein said Fc variant exhibits decreased binding to Fcγ

RIIIa as compared to the parent Fc polypeptide and wherein numbering is according to the EU index.

2. The protein according to claim 1, where said protein is an antibody or immunoadhesin.

3. The protein according to claim 2, where said protein is an antibody.

4. The protein according to claim 2, where said protein is an immunoadhesin.

5. A nucleic acid encoding a protein according to claim 1.

6. An expression vector comprising the nucleic acid of claim 5.

7. A host cell comprising a nucleic acid according to claim 5.

8. A method of making a protein comprising:

a) culturing a host cell according to claim 7 under conditions wherein said protein is produced; and

b) purifying said protein.