Granted Patent B2

US 11,401,348 · App. 16/539,986 · Granted Aug 2, 2022

Inventors: Gregory Lazar (Pacifica, CA); Gregory Moore (Azusa, CA)

Assignee: Xencor, Inc.

C07K16/468A61K47/6835C07K16/283C07K16/2809C07K16/2863C07K16/32C07K2317/31C07K2317/52C07K2317/64C07K2317/732C07K2317/92

Abstract

Claims (84)

1. A composition comprising a first and a second variant Fc domains of a parent IgG Fc polypeptide, wherein the first and second variant Fc domains are different, and wherein the first and the second variant Fc domains have amino acid substitutions selected from the following pairs:

A

B

K409E and

L368K;

S364D/K370G and

S364Y/K370R;

S364D and

Y349K;

K409D and

L368K;

K392E and

D399K;

S364E and

Y349K:

L368E/K409E and

L368K:

S364E/F405A and

Y349K/T394F;

S364H and

Y349K;

P395T/V397S/F405A and

T394F;

T394S/P395V/P396T/V397E/F405S and

T394F;

V397S/F405A and

T394F;

S364H/D401K/F405A and

Y349T/T394F/T411E;

L351K/S364H/D401K and

Y349T/L351E/T411E;

S364H and

Y349T;

S364H/D401K and

Y349T/T411E;

S364H/T394F and

Y349T/F405A;

S364H/F405A and

Y349T/T394F;

F405A and

T394F:

S364E/T394F and

Y349K/F405A;

V397T/F405S and

T394F;

S364E/F405S and

Y349K/T394Y;

S364E/T411E/F405A and

Y349K/T394F/D401K;

S364E/T411E and

Y349K/D401K;

L351E/S364D and

Y349K/L351K;

L351E/S364E and

Y349K/L351K;

Y349C/S364E and

Y349K/S354C;

S364H/F405A/T411E and

Y349T/T394F/D401K;

S364D/T394F and

Y349K/F405A

wherein numbering is according to the EU index as in Kabat, and

wherein the substitution(s) of column A and column B are in different variant Fc domains selected from the first variant Fc domain and the second variant Fc domain.

2. The composition of claim 1 , wherein the first and second variant Fc domains have amino acid substitutions selected from the following pairs:

C

D

S364E/F405A and

Y349K/T394F;

S364H/D401K and

Y349T/T411E;

S364H/T394F and

Y349T/F405A;

S364E/T394F and

Y349K/F405A;

S364E/T411E and

Y349K/D401K;

S364D/T394F and

Y349K/F405A;

S364H/F405A and

Y349T/T394F

wherein the substitution(s) of column C and column D are in different variant Fc domains selected from the first variant Fc domain and the second variant Fc domain.

3. The composition of claim 1 , wherein the first and second variant Fc domains further comprise at least one substitution that reduces binding to at least one FcγR receptor.

4. The composition of claim 1 , wherein the first and second variant Fc domains further comprise at least one substitution that increases binding to at least one FcγR receptor.

5. The composition of claim 1 , wherein the first and second variant Fc domains further comprise at least one substitution that increases binding to at least one FcRn receptor.

Assignments (1)

Continuity (4)

Cited By (12)

US 12,319,747 US 12,329,801 US 12,358,963 US 12,364,777 US 12,371,494 US 12,522,639 US 12,577,321 US 12,600,795 US 12,616,756 US 12,624,097 US 12,649,790 US 12,673,991