IP Library › Granted Patent US 8,409,568
Granted Patent B2
US 8,409,568 · App. 12/837,208 · Granted Apr 2, 2013

Mutant antibody Fc domains and fusion proteins thereof

Inventors: Changshou Gao (Potomac, MD); Herren Wu (Boyds, MD)
Assignee: MedImmune, LLC
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Quick Facts
Patent No.
US 8,409,568
App. No.
12/837,208
Granted
Apr 2, 2013
Kind
B2
Abstract

The present invention relates to a viral vector encoding for a library of antibodies or antibody fragments that are displayed on the cell membrane when expressed in a cell. The present invention provides cells comprising the viral vector nucleic acids and methods of screening the libraries for antibodies or antibody fragments with desired characteristics.

Claims (12)

1. An isolated antibody comprising a variant human IgG1 Fc region having a reduced affinity for an effector molecule wherein said human IgG1 Fc region comprises an amino acid substitution, insertion or combination thereof selected from the group consisting of: W277T; K246R/L251E/T260R; InR234/235; InV235/236; InR236/237; InR237/238; InV238/239; InN238/239; InL238/239; InE238/239; InG238/239; InS239/240; InG240/241; InE240/241; InG240/241/1198T; InL238/239/P238Q; InE238/239N348A; InS239/240/V266A; InR237/238/G236A, wherein the numbering is according to EU index as set forth in Kabat.

2. The antibody of claim 1 , wherein the effector molecule is selected from the group consisting of C1q, FcγRI, FcγRII and FcγRIIIA.

3. The antibody of claim 1 , wherein the antibody has reduced effector function.

4. The antibody of claim 3 , wherein the effector function is antibody-dependent cell-mediated cytotoxicity (ADCC.

5. The antibody of claim 1 , wherein the human IgG1 Fc region has a reduced affinity for C1q, FcγRI, FcγRII and FcγRIIIA.

6. The antibody of claim 3 , wherein the effector function is complement dependent cytotoxicity (CDC).

7. An Fc fusion protein comprising a human IgG1 Fc region having a reduced affinity for an effector molecule wherein said human IgG1 Fc region comprises an amino acid substitution, insertion or combination thereof selected from the group consisting of: W277T; K246R/L251E/T260R; InR234/235; InV235/236; InR236/237; InR237/238; InV238/239; InN238/239; InL238/239; InE238/239; InG238/239; InS239/240; InG240/241; InE240/241; InG240/241/1198T; InL238/239/P238Q; InE238/239N348A; InS239/240/V266A; InR237/238/G236A, wherein the numbering is according to EU index as set forth in Kabat.

8. The Fc fusion protein of claim 7 , wherein the effector molecule is selected from the group consisting of C1q, FcγRI, FcγRII and FcγRIIIA.

9. The Fc fusion protein of claim 7 , wherein the human IgG1 Fc region has a reduced affinity for C1q, FcγRI, FcγRII and FcγRIIIA.

10. The Fc fusion protein of claim 7 , wherein the antibody has reduced effector function.

11. The Fc fusion protein of claim 10 , wherein the effector function is ADCC.

12. The Fc fusion protein of claim 10 , wherein the effector function is CDC.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 25, 2014
From: GAO, CHANGSHOU; WU, HERREN
To: MEDIMMUNE, INC.
Reel/Frame 034259/0194 →
CHANGE OF NAME Recorded Nov 25, 2014
From: MEDIMMUNE, INC.
To: MEDIMMUNE, LLC
Reel/Frame 034469/0685 →
Continuity (3)
Division 11580005 · Oct 13, 2006
Provisional Application 60726161 · Oct 14, 2005
Related Publication 20100331208A1 · Dec 30, 2010