Anti-CD47 x anti-mesothelin antibodies and methods of use thereof

Patent metadata

Field	Value
Publication number	US-11260117-B2
Application number	US-201815991774-A
Country	US
Kind code	B2
Filing date	May 29, 2018
Priority date	May 26, 2017
Publication date	Mar 1, 2022
Grant date	Mar 1, 2022

Abstract

The invention also relates to novel bispecific antibodies carrying a different specificity for each binding site of the immunoglobulin molecule, where one of the binding sites is specific for CD47 and the second is specific for mesothelin (MSLN).

First claim

What is claimed is:

1. An isolated bispecific antibody comprising a first arm that specifically binds CD47 and a second arm that binds mesothelin (MSLN), wherein the bispecific antibody comprises two heavy chains each comprising a CDRH1 comprising the amino acid sequence of SEQ ID NO: 225, a CDRH2 comprising the amino acid sequence of SEQ ID NO: 226, a CDRH3 comprising the amino acid sequence of SEQ ID NO: 227,
one kappa light chain comprising a CDRL1 comprising the amino acid sequence of SEQ ID NO: 240, a CDRL2 comprising the amino acid sequence of SEQ ID NO: 242, and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 254, and
one lambda light chain comprising a combination of a CDRL1 amino acid sequence, a CDRL2 amino acid sequence, and a CDRL3 amino acid sequence selected from the group consisting of:
(a) a CDRL1 comprising the amino acid sequence of SEQ ID NO: 286, a CDRL2 comprising the amino acid sequence of SEQ ID NO: 292, and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 298;
(b) a CDRL1 comprising the amino acid sequence of SEQ ID NO: 282, a CDRL2 comprising the amino acid sequence of SEQ ID NO: 288, and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 294;
(c) a CDRL1 comprising the amino acid sequence of SEQ ID NO: 283, a CDRL2 comprising the amino acid sequence of SEQ ID NO: 289, and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 295;
(d) a CDRL1 comprising the amino acid sequence of SEQ ID NO: 284, a CDRL2 comprising the amino acid sequence of SEQ ID NO: 290, and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 296;
(e) a CDRL1 comprising the amino acid sequence of SEQ ID NO: 285, a CDRL2 comprising the amino acid sequence of SEQ ID NO: 291, and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 297;
(f) a CDRL1 comprising the amino acid sequence of SEQ ID NO: 287, a CDRL2 comprising the amino acid sequence of SEQ ID NO: 293, and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 299; and
(g) a CDRL1 comprising the amino acid sequence of SEQ ID NO: 282, a CDRL2 comprising the amino acid sequence of SEQ ID NO: 288, and a CDRL3 comprising the amino acid sequence of SEQ ID NO: 300.

2. The isolated bispecific antibody of claim 1 , wherein the bispecific antibody inhibits interaction between human CD47 and human signal-regulatory protein alpha (SIRPα).

3. The isolated bispecific antibody of claim 1 , wherein the first arm comprises a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 114 and a variable light chain comprising the amino acid sequence of SEQ ID NO: 168.

4. The isolated bispecific antibody of claim 1 , wherein the first arm comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 2 and a light chain comprising the amino acid sequence of SEQ ID NO: 56.

5. The isolated bispecific antibody of claim 1 , wherein isolated bispecific antibody comprises a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 114, a kappa variable light chain comprising the amino acid sequence of SEQ ID NO: 168, and a lambda variable light chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 212, 214, 216, 218, 220, 222, and 224.

6. The isolated bispecific antibody of claim 1 , wherein isolated bispecific antibody comprises a variable heavy chain comprising the amino acid sequence of SEQ ID NO: 114, and a combination of a kappa variable light chain and a lambda light chain selected from the group consisting of
(a) a kappa variable light chain comprising the amino acid sequence of SEQ ID NO: 168, and a lambda variable light chain comprising the amino acid sequence of SEQ ID NO: 212;
(b) a kappa variable light chain comprising the amino acid sequence of SEQ ID NO: 168, and a lambda variable light chain comprising the amino acid sequence of SEQ ID NO: 214;
(c) a kappa variable light chain comprising the amino acid sequence of SEQ ID NO: 168, and a lambda variable light chain comprising the amino acid sequence of SEQ ID NO: 216;
(d) a kappa variable light chain comprising the amino acid sequence of SEQ ID NO: 168, and a lambda variable light chain comprising the amino acid sequence of SEQ ID NO: 218;
(e) a kappa variable light chain comprising the amino acid sequence of SEQ ID NO: 168, and a lambda variable light chain comprising the amino acid sequence of SEQ ID NO: 220;
(f) a kappa variable light chain comprising the amino acid sequence of SEQ ID NO: 168, and a lambda variable light chain comprising the amino acid sequence of SEQ ID NO: 222; and
(g) a kappa variable light chain comprising the amino acid sequence of SEQ ID NO: 168, and a lambda variable light chain comprising the amino acid sequence of SEQ ID NO: 224.

7. The isolated bispecific antibody of claim 1 , wherein isolated bispecific antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 2, a kappa light chain comprising the amino acid sequence of SEQ ID NO: 56, and a lambda light chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 98, 100, 102, 104, 106, 108, and 110.

8. The isolated bispecific antibody of claim 1 , wherein isolated bispecific antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 2, and a combination of a kappa light chain and a lambda light chain selected from the group consisting of
(a) a kappa light chain comprising the amino acid sequence of SEQ ID NO: 56, and a lambda light chain comprising the amino acid sequence of SEQ ID NO: 98;
(b) a kappa light chain comprising the amino acid sequence of SEQ ID NO: 56, and a lambda light chain comprising the amino acid sequence of SEQ ID NO: 100;
(c) a kappa light chain comprising the amino acid sequence of SEQ ID NO: 56, and a lambda light chain comprising the amino acid sequence of SEQ ID NO: 102;
(d) a kappa light chain comprising the amino acid sequence of SEQ ID NO: 56, and a lambda light chain comprising the amino acid sequence of SEQ ID NO: 104;
(e) a kappa light chain comprising the amino acid sequence of SEQ ID NO: 56, and a lambda light chain comprising the amino acid sequence of SEQ ID NO: 106;
(f) a kappa light chain comprising the amino acid sequence of SEQ ID NO: 56, and a lambda light chain comprising the amino acid sequence of SEQ ID NO: 108; and
(g) a kappa light chain comprising the amino acid sequence of SEQ ID NO: 56, and a lambda light chain comprising the amino acid sequence of SEQ ID NO: 110.

9. The isolated bispecific antibody of claim 1 , wherein the bispecific antibody comprises two copies of a single heavy chain polypeptide and a first light chain and a second light chain, wherein the first and second light chains are different.

10. The isolated bispecific antibody of claim 9 , wherein at least a portion of the first light chain is of the Kappa type and at least a portion of the second light chain is of the Lambda type.

11. The isolated bispecific antibody of claim 10 , wherein the first light chain comprises at least a Kappa constant region.

12. The isolated bispecific antibody of claim 11 , wherein the first light chain further comprises a Kappa variable region.

13. The isolated bispecific antibody of claim 11 , wherein the first light chain further comprises a Lambda variable region.

14. The isolated bispecific antibody of claim 10 , wherein the second light chain comprises at least a Lambda constant region.

15. The isolated bispecific antibody of claim 14 , wherein the second light chain further comprises a Lambda variable region.

16. The isolated bispecific antibody of claim 14 , wherein the second light

Assignees

• Novimmune Sa

Inventors

• Masternak Krzysztof
• Fischer Nicolas

Classifications

• A61K39/001129

  Molecules with a "CD" designation not provided for elsewhere · CPC title

• A61K39/001168 Primary

  Mesothelin [MSLN] · CPC title

• A61K39/00 Primary

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• C07K16/30

  from tumour cells · CPC title

• C07K16/468

  Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies · CPC title