Granted Patent B2

US 12,486,311 · App. 17/736,917 · Granted Dec 2, 2025

Inventors: Gregory A. Lazar (Pacifica, CA); Matthew J. Bernett (Monrovia, CA)

Assignee: Xencor, Inc.

C07K14/70521C07K16/46C07K19/00A61K38/00C07K2319/30C07K2319/31C07K2319/74

Abstract

Claims (17)

1 . A CTLA-4-fusion protein comprising a variant CTLA-4 as compared to SEQ ID NO: 6 and an IgG Fc region,

wherein the variant CTLA-4 comprises amino acid substitutions A29H, T51N, L61E, and K93Q, and

wherein the IgG Fc region comprises M428L/N434S substitutions, wherein amino acid numbering is according to the EU index.

2 . The CTLA-4-fusion protein of claim 1 , wherein the variant CTLA-4 further comprises an E31I, E31T or E31M mutation.

3 . The CTLA-4-fusion protein of claim 1 , wherein the variant CTLA-4 further comprises an I106 mutation selected from I106E or I106Y.

4 . The CTLA-4-fusion protein of claim 1 , wherein the variant CTLA-4 further comprises a L104 mutation selected from L104V, L104M, L104F, L104H, L104D, L104E, L104W and L104Y.

5 . The CTLA-4-fusion protein of claim 1 , wherein the variant CTLA-4 further comprises a M53 mutation selected from M53W, M53F, M53Q, and M53Y.

6 . The CTLA-4-fusion protein of claim 1 , wherein the variant CTLA-4 further comprises a S64 mutation selected from S64K or S64R.

7 . The CTLA-4-fusion protein of claim 1 , wherein the variant CTLA-4 further comprises a T30 mutation selected from T30E, T30H, T30N, and T30R.

8 . The CTLA-4-fusion protein of claim 1 , wherein the variant CTLA-4 further comprises a T59 mutation selected from T59L.

9 . The CTLA-4-fusion protein of claim 1 , wherein the variant CTLA-4 further comprises a Y103 mutation selected from Y103E, Y103D, Y103F, Y103H, Y103N, and Y103Q.

10 . The CTLA-4-fusion protein of claim 1 , wherein the IgG is IgG1.

11 . The CTLA-4-fusion protein of claim 1 , wherein the IgG is IgG2.

12 . The CTLA-4-fusion protein of claim 1 , wherein the IgG is an IgG1/IgG2 hybrid.

13 . A method of inhibiting T cell activation in the presence of B7-expressing antigen presenting cells (APCs) comprising contacting said T cells with the variant CTLA-4-fusion protein of claim 1 .

14 . A cultured host cell comprising an expression vector comprising a nucleic acid encoding the variant CTLA-4 fusion protein of claim 1 .

15 . A method of making a variant CTLA-4-fusion protein comprising a) culturing the cultured host cell of claim 14 under conditions where said variant CTLA-4-fusion protein is produced; and b) purifying said variant CTLA-4-fusion protein.

Assignments (1)

Continuity (9)

References Cited (25)