Compositions and methods for treating IgE-mediated disorders

• US 9,540,451 B2
• Filed: 04/10/2013
• Issued: 01/10/2017
• Est. Priority Date: 09/17/2008
• Status: Active Grant

• Current Assignee: Xencor, Inc.
• Original Assignee: Xencor, Inc.
• Inventors: Desjarlais, John R., Chu, Seung Y., Horton, Holly M., Bernett, Matthew J.
• Primary Examiner(s): SZPERKA, MICHAEL EDWARD
• Application Number:
  US13/860,484
• Publication Number:
  US 20130203966A1
• Time in Patent Office: 1,371 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C07K 16/4291 against IgE
• CPC Class Codes: C07K 16/464 Igs containing CDR-residues from one specie grafted between FR-residues from another
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• 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 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The present invention relates to immunoglobulins that bind IgE and FcγRIIb with high affinity, said compositions being capable of inhibiting cells that express membrane-anchored IgE. Such compositions are useful for treating IgE-mediated disorders, including allergies and asthma.

Claims

1. An antibody comprising a variable region and variable Fc region as compared to a human IgG Fc region, wherein said variable region binds membrane anchored IgE, wherein the variable heavy chain of said variable region comprises SEQ ID NO:

17, wherein the variable light chain of said variable region comprises SEQ ID NO;

21, and wherein said Fc region is a variable Fc region comprising an amino acid substitution at position 267, wherein said substitution is 267E or 267D, and wherein said numbering is according to the EU index of Kabat.

2. An antibody according to claim 1 wherein said amino acid substitution of said variable Fc region is 267E.

3. An antibody according to claim 2, wherein said variable Fc region further comprises an amino acid substitution at position 328, wherein said substitution is 328F.

4. An antibody according to claim 2, wherein said Fc region further comprises an amino acid substitution at position 236, wherein said substitution is 236D.

5. An antibody according to claim 1 wherein said amino acid substitution of said variable Fc region is 267D.

6. An antibody according to claim 1, wherein the variable Fc region is a variable human IgG1 Fc region.