IP Library › Granted Patent US 11,827,713
Granted Patent B2
US 11,827,713 · App. 16/626,721 · Granted Nov 28, 2023

Chimeric antibody immune effector cell engagers and methods of use thereof

Inventors: Xiaohu Fan (Edmonton, CA); Qiuchuan Zhuang (Nanjing, CN); Lei Yang (Huainan, CN); Pingyan Wang (Fengyang, CN); Qingyan Li (Nanjing, CN)
Assignee: Nanjing Legend Biotech Co., Ltd.
C07K16/2896A61P35/00C07K14/765C07K16/2809C07K16/2878A61K2039/505C07K2317/24C07K2317/31C07K2317/565C07K2317/569C07K2317/622C07K2317/73C07K2317/92C07K2319/02C07K2319/30
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Quick Facts
Patent No.
US 11,827,713
App. No.
16/626,721
Granted
Nov 28, 2023
Kind
B2
Abstract

Provided is a chimeric antibody immune cell engager comprising a target cell binding domain that specifically binds to an antigen on a target cell, and an immune effector cell binding domain comprising an antigen-binding fragment that specifically binds to an antigen on an immune effector cell. Also provided are pharmaceutical compositions, kits and methods of treatment.

Claims (69)

1. A chimeric antibody immune effector cell engager comprising:

(a) a target cell binding domain, wherein the target cell binding domain comprises an anti-BCMA single-domain antibody (sdAb) comprising:

(1) a CDR1 comprising the amino acid sequence of SEQ ID NO:1; a CDR2 comprising the amino acid sequence of SEQ ID NO:12; and a CDR3 comprising the amino acid sequence of SEQ ID NO:23;

(2) a CDR1 comprising the amino acid sequence of SEQ ID NO:2; a CDR2 comprising the amino acid sequence of SEQ ID NO:13; and a CDR3 comprising the amino acid sequence of SEQ ID NO:24;

(3) a CDR1 comprising the amino acid sequence of SEQ ID NO:3; a CDR2 comprising the amino acid sequence of SEQ ID NO:14; and a CDR3 comprising the amino acid sequence of SEQ ID NO:25;

(4) a CDR1 comprising the amino acid sequence of SEQ ID NO:4; a CDR2 comprising the amino acid sequence of SEQ ID NO:15; and a CDR3 comprising the amino acid sequence of SEQ ID NO:26;

(5) a CDR1 comprising the amino acid sequence of SEQ ID NO:5; a CDR2 comprising the amino acid sequence of SEQ ID NO:16; and a CDR3 comprising the amino acid sequence of SEQ ID NO:27;

(6) a CDR1 comprising the amino acid sequence of SEQ ID NO:6; a CDR2 comprising the amino acid sequence of SEQ ID NO:17; and a CDR3 comprising the amino acid sequence of SEQ ID NO:28;

(7) a CDR1 comprising the amino acid sequence of SEQ ID NO:7; a CDR2 comprising the amino acid sequence of SEQ ID NO:18; and a CDR3 comprising the amino acid sequence of SEQ ID NO:29;

(8) a CDR1 comprising the amino acid sequence of SEQ ID NO:8; a CDR2 comprising the amino acid sequence of SEQ ID NO:19; and a CDR3 comprising the amino acid sequence of SEQ ID NO:30;

(9) a CDR1 comprising the amino acid sequence of SEQ ID NO:9; a CDR2 comprising the amino acid sequence of SEQ ID NO:20; and a CDR3 comprising the amino acid sequence of SEQ ID NO:31;

(10) a CDR1 comprising the amino acid sequence of SEQ ID NO:10; a CDR2 comprising the amino acid sequence of SEQ ID NO:21; and a CDR3 comprising the amino acid sequence of SEQ ID NO:32; or

(11) a CDR1 comprising the amino acid sequence of SEQ ID NO:11; a CDR2 comprising the amino acid sequence of SEQ ID NO:22; and a CDR3 comprising the amino acid sequence of SEQ ID NO:33; and,

(b) an immune effector cell binding domain comprising an anti-CD3 antigen-binding fragment.

2. The chimeric antibody immune effector cell engager of claim 1 , wherein the sdAb is camelid, chimeric, or humanized.

3. The chimeric antibody immune effector cell engager of claim 1 , wherein the sdAb is a V H H fragment.

4. A chimeric antibody immune effector cell engager comprising:

(a) a target cell binding domain, wherein the target cell binding domain comprises an anti-CD38 single domain antibody (sdAb) comprising:

(1) a CDR1 comprising the amino acid sequence of SEQ ID NO:34; a CDR2 comprising the amino acid sequence of SEQ ID NO:46; and a CDR3 comprising the amino acid sequence of SEQ ID NO:58;

(2) a CDR1 comprising the amino acid sequence of SEQ ID NO:35; a CDR2 comprising the amino acid sequence of SEQ ID NO:47; and a CDR3 comprising the amino acid sequence of SEQ ID NO:59;

(3) a CDR1 comprising the amino acid sequence of SEQ ID NO:36; a CDR2 comprising the amino acid sequence of SEQ ID NO:48; and a CDR3 comprising the amino acid sequence of SEQ ID NO:60;

(4) a CDR1 comprising the amino acid sequence of SEQ ID NO:37; a CDR2 comprising the amino acid sequence of SEQ ID NO:49; and a CDR3 comprising the amino acid sequence of SEQ ID NO:61;

(5) a CDR1 comprising the amino acid sequence of SEQ ID NO:38; a CDR2 comprising the amino acid sequence of SEQ ID NO:50; and a CDR3 comprising the amino acid sequence of SEQ ID NO:62;

(6) a CDR1 comprising the amino acid sequence of SEQ ID NO:39; a CDR2 comprising the amino acid sequence of SEQ ID NO:51; and a CDR3 comprising the amino acid sequence of SEQ ID NO:63;

(7) a CDR1 comprising the amino acid sequence of SEQ ID NO:40; a CDR2 comprising the amino acid sequence of SEQ ID NO:52; and a CDR3 comprising the amino acid sequence of SEQ ID NO:64;

(8) a CDR1 comprising the amino acid sequence of SEQ ID NO:41; a CDR2 comprising the amino acid sequence of SEQ ID NO:53; and a CDR3 comprising the amino acid sequence of SEQ ID NO:65;

(9) a CDR1 comprising the amino acid sequence of SEQ ID NO:42; a CDR2 comprising the amino acid sequence of SEQ ID NO:54; and a CDR3 comprising the amino acid sequence of SEQ ID NO:66;

(10) a CDR1 comprising the amino acid sequence of SEQ ID NO:43; a CDR2 comprising the amino acid sequence of SEQ ID NO:55; and a CDR3 comprising the amino acid sequence of SEQ ID NO:67; or

(11) a CDR1 comprising the amino acid sequence of SEQ ID NO:44; a CDR2 comprising the amino acid sequence of SEQ ID NO:56; and a CDR3 comprising the amino acid sequence of SEQ ID NO:68; and,

(b) an immune effector cell binding domain comprising an anti-CD3 antigen-binding fragment.

5. The chimeric antibody immune effector cell engager of claim 1 , wherein the target cell binding domain comprises an anti-BCMA sdAb that specifically binds to BCMA and an anti-CD38 sdAb that specifically binds to CD38.

6. The chimeric antibody immune effector cell engager of claim 1 , wherein the target cell binding domain comprises a first anti-BCMA sdAb and a second anti-BCMA sdAb.

7. The chimeric antibody immune effector cell engager of claim 1 , wherein the target cell binding domain is fused to the N-terminus of the immune effector cell binding domain, or wherein the target cell binding domain is fused to the C-terminus of the immune effector cell binding domain.

8. The chimeric antibody immune effector cell engager of claim 1 , wherein the immune effector cell is a T cell or an NK cell.

9. The chimeric antibody immune effector cell engager of claim 1 , wherein the anti-CD3 antigen-binding fragment is derived from OKT3, L2K, UCHT1, 60E11, or 117G03.

10. An isolated nucleic acid comprising a nucleic acid sequence encoding the chimeric antibody immune effector cell engager of claim 1 .

11. A vector comprising the isolated nucleic acid of claim 10 .

12. A pharmaceutical composition, comprising the chimeric antibody immune effector cell engager of claim 1 , and a pharmaceutically acceptable carrier.

13. A method of treating a BCMA-expressing cancer in an individual, comprising administering to the individual an effective amount of the pharmaceutical composition of claim 12 .

14. The chimeric antibody immune effector cell engager of claim 4 , wherein the anti-CD3 antigen-binding fragment is derived from OKT3, L2K, UCHT1, 60E11, or 117G03.

15. The chimeric antibody immune effector cell engager of claim 1 , wherein the anti-BCMA sdAb comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 78-88 and 290-316.

16. The chimeric antibody immune effector cell engager of claim 4 , wherein the anti-CD38 sdAb comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 89-100.

17. The chimeric antibody immune effector cell engager of claim 1 , wherein the anti-CD3 binding fragment is a V H H or an scFv.

18. The chimeric antibody immune effector cell engager of claim 4 , wherein the anti-CD3 binding fragment is a V H H or an scFv.

19. The chimeric antibody immune effector cell engager of claim 1 , wherein the anti-CD3 binding fragment comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 103-105 and 182-183.

20. The chimeric antibody immune effector cell engager of claim 4 , wherein the anti-CD3 binding fragment comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 103-105 and 182-183.

21. The chimeric antibody immune effector cell engager of claim 5 , wherein the chimeric antibody immune effector cell engager comprises an the amino acid sequence selected from the group consisting of SEQ ID NOs: 160-163 and 206-207.

22. The chimeric antibody immune effector cell engager of claim 5 , wherein the chimeric antibody immune effector cell engager comprises:

a) a target binding domain comprising:

(i) an anti-BCMA sdAb comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:1; a CDR2 comprising the amino acid sequence of SEQ ID NO:12; and a CDR3 comprising the amino acid sequence of SEQ ID NO:23; and

(ii) an anti-CD38 sdAb comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:38; a CDR2 comprising the amino acid sequence of SEQ ID NO:50; and a CDR3 comprising the amino acid sequence of SEQ ID NO:62; and, b) an immune effector cell binding domain comprising an anti-CD3 V H H comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 317; a CDR2 comprising the amino acid sequence of SEQ ID NO: 318; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 319.

23. The chimeric antibody immune effector cell engager of claim 5 , wherein the chimeric antibody immune effector cell engager comprises:

a) a target binding domain comprising:

(i) an anti-BCMA sdAb comprising the amino acid sequence of SEQ ID NO: 78; and

(ii) an anti-CD38 sdAb comprising the amino acid sequence of SEQ ID NO: 93; and,

b) an immune effector cell binding domain comprising an anti-CD3 V H H comprising the amino acid sequence of SEQ ID NO: 182.

24. The chimeric antibody immune effector cell engager of claim 5 , wherein the chimeric antibody immune effector cell engager comprises:

a) a target binding domain comprising:

(i) an anti-BCMA sdAb comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:1; a CDR2 comprising the amino acid sequence of SEQ ID NO:12; and a CDR3 comprising the amino acid sequence of SEQ ID NO:23; and

(ii) an anti-CD38 sdAb comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:38; a CDR2 comprising the amino acid sequence of SEQ ID NO:50; and a CDR3 comprising the amino acid sequence of SEQ ID NO:62; and,

b) an immune effector cell binding domain comprising an anti-CD3 V H H comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 320; a CDR2 comprising the amino acid sequence of SEQ ID NO: 321; and a CDR3 comprising the amino acid sequence of SEQ ID NO: 322.

25. The chimeric antibody immune effector cell engager of claim 5 , wherein the chimeric antibody immune effector cell engager comprises:

a) a target binding domain comprising:

(i) an anti-BCMA sdAb comprising the amino acid sequence of SEQ ID NO: 78; and

(ii) an anti-CD38 sdAb comprising the amino acid sequence of SEQ ID NO: 93; and,

b) an immune effector cell binding domain comprising an anti-CD3 V H H comprising the amino acid sequence of SEQ ID NO: 183.

26. A pharmaceutical composition, comprising the chimeric antibody immune effector cell engager of claim 4 , and a pharmaceutically acceptable carrier.

27. The chimeric antibody immune effector cell engager of claim 1 , wherein the anti-BCMA sdAb comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:1; a CDR2 comprising the amino acid sequence of SEQ ID NO:12; and a CDR3 comprising the amino acid sequence of SEQ ID NO:23.

28. The chimeric antibody immune effector cell engager of claim 4 , wherein the anti-CD38 sdAb comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:38; a CDR2 comprising the amino acid sequence of SEQ ID NO:50; and a CDR3 comprising the amino acid sequence of SEQ ID NO:62.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 26, 2019
From: FAN, XIAOHU; ZHUANG, QIUCHUAN; YANG, LEI; WANG, PINGYAN; LI, QINGYAN
To: NANJING LEGEND BIOTECH CO., LTD.
Reel/Frame 051372/0243 →
Priority Claims (1)
WO PCT/CN2017/090343 · Jun 27, 2017 · international
Continuity (1)
Related Publication 20200123269A1 · Apr 23, 2020