IP Library › Granted Patent US 9,834,604
Granted Patent B2
US 9,834,604 · App. 14/128,461 · Granted Dec 5, 2017

Inhibitors of T-cell activation

Inventors: Yunxiang Zhu (Bridgewater, NJ); Jozsef Karman (Bridgewater, NJ); Ronnie Wei (Bridgewater, NJ); Canwen Jiang (Southborough, MA); Seng Cheng (Bridgwater, NJ)
Assignee: GENZYME CORPORATION
C07K16/2803C07K14/47C07K14/70532C07K14/70539C07K2319/00
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Quick Facts
Patent No.
US 9,834,604
App. No.
14/128,461
Granted
Dec 5, 2017
Kind
B2
Abstract

The present invention provides a bispecific biologic comprising a ligand specific for CTLA-4 and a ligand specific for a pMHC complex.

Claims (13)

1. A bispecific fusion protein comprising a ligand specific for CTLA-4 selected from the group consisting of CD80 (B7-1) and CD86 (B7-2), and a ligand specific for a peptide-MHC class II (pMHCII) complex, wherein the CD80 or the CD86 and the ligand specific for the pMHCII complex are spaced apart by a linker.

2. The bispecific fusion protein according to claim 1 , wherein the ligand specific for the pMHCII complex is LAG-3.

3. The bispecific fusion protein according to claim 1 , wherein the linker is one or more of a polyamino acid sequence and an antibody Fc domain.

4. The bispecific fusion protein according to claim 3 , wherein the polyamino acid sequence is G9 (Gly-9).

5. The bispecific fusion protein according to claim 1 , wherein the ligand specific for CTLA-4 is CD80.

6. The bispecific fusion protein according to claim 5 , wherein the CD80 is mutated to increase specificity for CTLA-4 over CD28.

7. The bispecific fusion protein according to claim 6 , wherein CD80 is human CD80 comprising the amino acid sequence SEQ ID NO:15 modified to include at least one of mutations W84A, K71G, K71V, S109G, R123S, R123D, G124L, S190A, S201A, R63A, M81A, N97A and E196A.

8. The bispecific fusion protein according to claim 7 , wherein CD80 comprises the mutation W84A or E196A of human CD80.

9. The bispecific fusion protein according to claim 2 , wherein LAG-3 is mutated to increase specificity for pMHCII.

10. The bispecific fusion protein according to claim 9 , wherein LAG-3 is human LAG-3 comprising at least one of mutations R73E, R75A, R75E and R76E.

11. The bispecific fusion protein according to claim 10 , wherein LAG-3 comprises the mutation R75A or R75E.

12. The bispecific fusion protein according to claim 1 , wherein the ligand specific for the pMHCII complex is an anti-MHCII antibody.

13. The bispecific fusion protein according to claim 1 , wherein the ligand specific for CTLA-4 is CD86.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 9, 2016
From: ZHU, YUNXIANG; KARMAN, JOZSEF; WEI, RONNIE; JIANG, CANWEN; CHENG, SENG
To: GENZYME CORPORATION
Reel/Frame 038853/0071 →
Continuity (2)
Provisional Application 61503282 · Jun 30, 2011
Related Publication 20140348832A1 · Nov 27, 2014