Engineering of an antibody for tumor-selective binding of CD47

Patent metadata

Field	Value
Publication number	US-12428488-B2
Application number	US-202017594131-A
Country	US
Kind code	B2
Filing date	Apr 3, 2020
Priority date	Apr 5, 2019
Publication date	Sep 30, 2025
Grant date	Sep 30, 2025

Abstract

Antibodies are provided which comprise at least one Fab portion that binds CD47 and at least one Fab portion that binds the tumor associated antigen (TAA) CD20; wherein the Fab portion that binds CD47 exhibits low affinity for CD47; and, wherein the Fab portion that binds CD20 exhibits high affinity for CD20; and, wherein the antibody selectively binds CD47 and blocks CD47 interaction with SIRPα in tumor cells while exhibiting no substantial binding to CD47 in normal cells.

First claim

What is claimed is:

1. A bispecific antibody comprising at least one Fab portion that binds CD47 and at least one Fab portion that binds CD20; wherein the Fab portion that binds CD47 comprises:
(i) a light chain variable region (VL) region comprising VL CDRs RASQGISSWLA (SEQ ID NO:377), AASVLES (SEQ ID NO:378), and QQANSFPYT (SEQ ID NO: 379); and
(ii) a heavy chain variable region (VH) region comprising VH CDRs NFVMS (SEQ ID NO: 380), TISGSGGSTYYADSVKG (SEQ ID NO:381), and HYILRYFD (SEQ ID NO: 382);
wherein the bispecific antibody selectively binds B cells; and
wherein the bispecific antibody is isotype IgG1.

2. A bispecific antibody according to claim 1 wherein the bispecific antibody comprises an anti-CD47 light chain (LC) constant region comprising SEQ ID NO:340.

3. A bispecific antibody according to claim 2 wherein the bispecific antibody comprises an anti-CD47 heavy chain (HC) constant region comprising SEQ ID NO:342.

4. A bispecific antibody according to claim 1 that selectively binds malignant B cells.

5. A bispecific antibody according to claim 3 that selectively binds malignant B cells.

6. A bispecific antibody according to claim 5 wherein the bispecific antibody comprises an anti-CD20 light chain (LC) constant region comprising SEQ ID NO:344.

7. A bispecific antibody according to claim 6 wherein the bispecific antibody comprises an anti-CD20 heavy chain (HC) constant region comprising SEQ ID NO:346.

8. A bispecific antibody according to claim 1 comprising a VL region comprising SEQ ID NO:383; and, a VH region comprising SEQ ID NO:384.

9. A bispecific antibody according to claim 7 comprising anti-CD20 VL CDRs RASSSVSYIH (SEQ ID NO:353), ATSNLAS (SEQ ID NO:354), QQWTSNPPT (SEQ ID NO:355); and, VH CDRs SYNMH (SEQ ID NO:356), AIYPGNGDTSYNQKFKG (SEQ ID NO:357), STYYGGDWYFNV (SEQ ID NO:358).

10. A bispecific antibody according to claim 9 comprising an anti-CD20 VL region comprising SEQ ID NO: 323 and a VH region comprising SEQ ID NO: 324.

11. A bispecific antibody according to claim 10 comprising an anti-CD20 LC region comprising SEQ ID NO:331 and an anti-CD20 HC region comprising SEQ ID NO: 332.

12. A bispecific antibody according to claim 8 comprising anti-CD20 VL CDRs RASSSVSYIH (SEQ ID NO:353), ATSNLAS (SEQ ID NO:354), QQWTSNPPT (SEQ ID NO:355); and, VH CDRs SYNMH (SEQ ID NO:356), AIYPGNGDTSYNQKFKG (SEQ ID NO:357), STYYGGDWYFNV (SEQ ID NO:358).

13. A bispecific antibody according to claim 12 comprising an anti-CD20 VL region comprising SEQ ID NO: 323 and a VH region comprising SEQ ID NO: 324.

14. A bispecific antibody according to claim 13 comprising an anti-CD20 LC region comprising SEQ ID NO:331 and an anti-CD20 HC region comprising SEQ ID NO:332.

15. A bispecific antibody according to claim 14 comprising an anti-CD47 LC region comprising SEQ ID NO:385 and an anti-CD47 HC region comprising SEQ ID NO:386.

16. A pharmaceutical composition for administration to a patient in need thereof comprising
i) the bispecific antibody of claim 1 ; and
ii) at least one pharmaceutically acceptable carrier.

17. A method of treating a B-cell malignancy in a patient comprising administering an effective amount of the bispecific antibody of claim 1 .

Assignees

• Celgene Corp

Inventors

• Hadjivassiliou Haralambos
• Zhu Dan
• Sun Jeonghoon
• Acharya Sharmistha
• Johnson Jeffrey
• Chan Henry
• Hariharan Kandasamy
• Cho Ho

Classifications

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/734

  Complement-dependent cytotoxicity [CDC] · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title