IP Library Granted Patent US 8,753,628
Granted Patent B2
US 8,753,628 · App. 13/915,608 · Granted Jun 17, 2014

Optimized Fc variants

Inventors: Gregory Alan Lazar (Indianapolis, IN); Wei Dang (Pasadena, CA); John Desjarlais (Pasadena, CA); Sher Bahadur Karki (Santa Monica, CA); Omid Vafa (Monrovia, CA); Robert Hayes (Paoli, PA); Jost Vielmetter (Altadena, CA)
Assignee: Xencor, Inc.
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Quick Facts
Patent No.
US 8,753,628
App. No.
13/915,608
Granted
Jun 17, 2014
Kind
B2
Abstract

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

Claims (14)

1. A method of altering effector function in a subject, comprising administering to the subject a polypeptide comprising an Fc variant of a human parent IgG1 Fc polypeptide, wherein said Fc variant comprises an amino acid substitution in the Fc region of said parent Fc polypeptide at position 243, wherein said numbering is according to the EU index in Kabat.

2. The method according to claim 1 , wherein said polypeptide is an antibody.

3. The method according to claim 1 , wherein said polypeptide comprises an engineered glycoform.

4. The method according to claim 1 , wherein said amino acid substitution is 243L.

5. The method according to claim 1 , wherein said amino acid substitution is 243L and said Fc variant exhibits decreased binding to FcγRIIIa as compared to the human parent IgG1 Fc polypeptide.

6. The method according to claim 1 , wherein said amino acid substitution is 243E.

7. The method according to claim 1 , wherein said amino acid substitution is 243E and said Fc variant exhibits decreased binding to FcγRIIIa as compared to the human parent IgG1 Fc polypeptide.

8. The method according to claim 1 , wherein said amino acid substitution is 243W.

9. The method according to claim 1 , wherein said amino acid substitution is 243W and said Fc variant exhibits increased binding to FcγRIIIa as compared to the human parent IgG1 Fc polypeptide.

10. The method according to claim 2 , wherein said antibody has specificity for a target antigen selected from the group consisting of CD19, CD20, CD22, CD30, CD33, CD40, CD40L, CD52, Her2/neu, EGFR, EpCAM, MUC1, GD3, CEA, CA 125, IgE, HLA-DR, TNFalpha, MUC18, prostate specific membrane antigen (PMSA) and VEGF.

11. The method according to claim 2 , wherein said antibody has specificity for Her2/neu.

12. The method according to claim 2 , wherein said subject has cancer.

13. The method according to claim 1 , wherein said subject has an autoimmune disorder.

14. The method according to claim 1 , wherein said subject has an inflammatory disorder.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 6, 2014
From: VIELMETTER, JOST
To: XENCOR, INC.
Reel/Frame 032365/0001 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 6, 2014
From: LAZAR, GREGORY ALAN; DANG, WEI; DESJARLAIS, JOHN R.; KARKI, SHER BAHADUR; VAFA, OMID; HAYES, ROBERT
To: XENCOR, INC.
Reel/Frame 032365/0259 →
Continuity (14)
Division 13870781 · Apr 25, 2013
Continuation 12896610 · Oct 1, 2010
Continuation 11124620 · May 5, 2005
Continuation In Part 10822231 · Mar 26, 2004
Continuation In Part 10672280 · Sep 26, 2003
Provisional Application 60627774 · Nov 12, 2004
Provisional Application 60626991 · Nov 10, 2004
Provisional Application 60627026 · Nov 9, 2004
Provisional Application 60589906 · Jul 20, 2004
Provisional Application 60477839 · Jun 12, 2003
Provisional Application 60467606 · May 2, 2003
Provisional Application 60442301 · Jan 23, 2003
Provisional Application 60414433 · Sep 27, 2002
Related Publication 20130273043A1 · Oct 17, 2013