Bispecific antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-2025074982-A1
Application number	US-202418818983-A
Country	US
Kind code	A1
Filing date	Aug 29, 2024
Priority date	Aug 29, 2023
Publication date	Mar 6, 2025
Grant date	—

Abstract

Provided herein are, inter alia, antibody compounds comprising an anti-immune cell antibody (e.g., anti-CD3 antibody) covalently bound to a CS-1-binding antibody; immune cells bound to compounds comprising an anti-immune cell antibody (e.g., anti-CD3 antibody) covalently bound to a CS-1-binding antibody; humanized OKT3 antibodies; pharmaceutical compositions; and methods for treating cancer, such as multiple myeloma.

First claim

What is claimed is:

1 . A compound comprising an anti-CD3 antibody covalently bound to a CS-1-binding antibody.

2 . The compound of claim 1 , wherein the anti-CD3 antibody comprises an OKT3 antibody and the CS-1-binding antibody comprises elotuzumab.

3 . The compound of claim 2 , wherein the anti-CD3 antibody comprises:
(i) a light chain variable domain CDR 1 as set forth in SEQ ID NO:1, CDR 2 as set forth in SEQ ID NO:2 and CDR 3 as set forth in SEQ ID NO:3; and (ii) a heavy chain variable domain CDR 1 as set forth in SEQ ID NO:4, CDR 2 as set forth in SEQ ID NO:5 and CDR 3 as set forth in SEQ ID NO:6.

4 . The compound of claim 3 , wherein anti-CD3 antibody comprises:
(i) a light chain variable domain having at least 95% sequence identity to SEQ ID NO:9; and (ii) a heavy chain variable domain having at least 95% sequence identity to SEQ ID NO:10.

5 . The compound of claim 4 , wherein the anti-CD3 antibody comprises:
(i) a light chain variable domain having SEQ ID NO:9; and (ii) a heavy chain variable domain having SEQ ID NO:10.

6 . The compound of claim 4 , wherein:
(i) the 5′ end of the light chain variable domain further comprises a signal sequence as set forth in SEQ ID NO:7; and (ii) the 5′ end of the heavy chain variable domain further comprises a signal sequence as set forth in SEQ ID NO:8.

7 . The compound of claim 2 , wherein the CS-1-binding antibody comprises:
(i) a light chain variable domain CDR L1 as set forth in SEQ ID NO:15, CDR L2 as set forth in SEQ ID NO:16, and CDR L3 as set forth in SEQ ID NO:17; and (ii) a heavy chain variable domain CDR H1 as set forth in SEQ ID NO:19, CDR H2 as set forth in SEQ ID NO:20, and CDR H3 as set forth in SEQ ID NO:21.

8 . The compound of claim 2 , wherein the CS-1-binding antibody comprises:
(i) a light chain variable domain having at least 95% sequence identity to SEQ ID NO:14; and (ii) a heavy chain variable domain having at least 95% sequence identity to SEQ ID NO:18.

9 . The compound of claim 8 , wherein the CS-1-binding antibody comprises:
(i) a light chain variable domain having SEQ ID NO:14; and (ii) a heavy chain variable domain having SEQ ID NO:18.

10 . The compound of claim 8 , wherein the CS-1-binding antibody comprises a light chain having at least 95% sequence identity to SEQ ID NO:12 and a heavy chain having at least 95% sequence identity to SEQ ID NO:13.

11 . The compound of claim 10 , wherein the CS-1-binding antibody comprises a light chain having SEQ ID NO:12 and a heavy chain having SEQ ID NO:13.

12 . The compound of claim 1 , wherein the CS-1-binding antibody comprises SEQ ID NO:11.

13 . The compound of claim 1 , wherein the anti-CD3 antibody is an antibody, a F(ab′) fragment, a F(ab′) 2 fragment, or a single chain variable domain; and wherein the CS-1-binding antibody is an antibody, a F(ab′) fragment, a F(ab′) 2 fragment, or a single chain variable domain.

14 . The compound of claim 1 , wherein a cysteine residue in the anti-CD3 antibody is covalently bound to a cysteine residue in the CS-1-binding antibody.

15 . The compound of claim 1 , wherein a cysteine residue in the hinge region of the anti-CD3 antibody is covalently bound to a cysteine residue in the hinge region of the CS-1-binding antibody.

16 . The compound of claim 1 , wherein a cysteine residue in the anti-CD3 antibody is covalently bound to a cysteine residue in the CS-1-binding antibody via a linking group of the formula: -L 1 -L 2 -L 3 -, wherein L 1 , L 2 , and L 3 are each independently a bond, an amino acid, a peptide, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene;

17 . The compound of claim 1 , wherein a cysteine residue in the hinge region of the anti-CD3 antibody is covalently bound to a cysteine residue in the hinge region of the CS-1-binding antibody via a linking group of the formula: -L 1 -L 2 -L 3 -, wherein L 1 is a 2 to 12 membered substituted or unsubstituted heteroalkylene; L 2 is a substituted or unsubstituted fused heteroarylene having from 2 to 4 rings fused together; and L 3 is —W(OCH 2 CH 2 ) n where W is a bond or unsubstituted C 1-6 alkylene and n is an integer from 1 to 100; wherein L 1 is covalently bound to the cysteine residue in the hinge region of the anti-CD3 antibody and L 3 is covalently bound to the cysteine residue in the hinge region of the CS-1-binding antibody.

18 . The compound of claim 1 , wherein the compound is non-covalently bound to an immune cell, wherein the immune cell is a T cell, a B cell, a natural killer cell, a monocyte, a neutrophil, a macrophage, or a genetically-engineered immune cell.

19 . A composition comprising the compound of claim 1 and
(i) a pharmaceutically acceptable excipient;
(ii) an immune cell selected from the group consisting of a T cell, a B cell, a natural killer cell, a monocyte, a neutrophil, a macrophage, or a genetically-engineered immune cell; or
(iii) a pharmaceutically acceptable excipient and an immune cell selected from the group consisting of a T cell, a B cell, a natural killer cell, a monocyte, a neutrophil, a macrophage, or a genetically-engineered immune cell.

20 . A method of treating multiple myeloma in a patient in need thereof, the method comprising administering to the patient an effective amount of the compound of claim 1 , thereby treating multiple myeloma in the patient.

Assignees

• Hope City

Inventors

• Wang Xiuli
• Shively John Ernest
• Awuah Dennis
• Kujawski Maciej
• Li Lin
• Yazaki Paul

Classifications

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K2317/53

  Hinge · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K16/2803

  against the immunoglobulin superfamily · CPC title