Anti-NTB-A antibodies and related compositions and methods

• US 9,708,404 B2
• Filed: 12/20/2013
• Issued: 07/18/2017
• Est. Priority Date: 12/21/2012
• Status: Active Grant

• Current Assignee: Seagen Inc.
• Original Assignee: Seattle Genetics Incorporated
• Inventors: Lewis, Timothy S, Law, Che-Leung
• Primary Examiner(s): BRISTOL, LYNN ANNE
• Application Number:
  US14/758,430
• Publication Number:
  US 20150376276A1
• Time in Patent Office: 1,306 Days
• Field of Search: 4241331, 4241721, 5303873, 53038822, 5303917
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 2317/20 characterized by taxonomic origin
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/64 comprising a combination of variable region and constant region components
• CPC Class Codes: C07K 2317/71 Decreased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/77 Internalization into the cell
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

Disclosed are antibodies, including antibody drug conjugates, that specifically bind to NTB-A. Also disclosed are methods for using the anti-NTB-A antibodies to detect or modulate activity of (e.g., inhibit proliferation of) an NTB-A-expressing cell, as well as for diagnoses or treatment of diseases or disorders (e.g., cancer) associated with NTB-A-expressing cells. Further disclosed is a method of treating multiple myeloma using an anti-NTB-A antibody drug conjugate, which optionally includes an anti-NTB-A antibody as disclosed herein.

Claims

1. An isolated monoclonal antibody that specifically binds to human NTB-A (SLAMF6), wherein the antibody comprises:

a CDR-H1 amino acid sequence as shown in SEQ ID NO;

5 or SEQ ID NO;

11;

a CDR-H2 amino acid sequence as shown in SEQ ID NO;

6 or SEQ ID NO;

12;

a CDR-H3 amino acid sequence as shown in SEQ ID NO;

7 or SEQ ID NO;

13;

a CDR-L1 amino acid sequence as shown in SEQ ID NO;

8 or SEQ ID NO;

14;

a CDR-L2 amino acid sequence as shown in SEQ ID NO;

9 or SEQ ID NO;

15; and

a CDR-L3 amino acid sequence as shown in SEQ ID NO;

10 or SEQ ID NO;

16.

2. The antibody of claim 1, further comprising at least a portion of an immunoglobulin heavy chain constant region.

3. The antibody of claim 1, wherein the antibody further comprises VH and VL domains having amino acid sequences as respectively shown in residues 20-135 of SEQ ID NO:

1 and residues 21-140 of SEQ ID NO;

2.

4. The antibody of claim 3, wherein the antibody comprises a first polypeptide chain comprising the VH domain and a second polypeptide chain comprising the VL domain, the first polypeptide chain further comprising at least a portion of an immunoglobulin heavy chain constant region fused to the VH domain, and the second polypeptide chain further comprising at least a portion of an immunoglobulin light chain constant region fused to the VL domain.

5. The antibody of claim 2, wherein the heavy chain constant region is a mutant form of a natural human constant region having reduced binding to an Fcγ

receptor relative to the natural human constant region.

6. The antibody of claim 2, wherein the heavy chain constant region is of an isotype selected from the group consisting of human isotypes IgG1, IgG2, IgG3, and IgG4.

7. The antibody of claim 1, wherein the antibody is conjugated to a cytotoxic or cytostatic agent.

8. The antibody of claim 4, wherein the heavy chain constant region is a mutant form of a natural human constant region having reduced binding to an Fcγ

receptor relative to the natural human constant region.

9. A pharmaceutical composition comprising:

the antibody of claim 1; and

a pharmaceutically compatible ingredient.

10. An isolated murine monoclonal antibody comprising VH and VL domains having amino acid sequences as respectively shown in residues 20-135 of SEQ ID NO:

1 and residues 21-140 of SEQ ID NO;

2, or a chimeric or humanized form thereof.

11. An antibody drug conjugate comprising an antibody conjugated to a cytotoxic agent, wherein the antibody comprises VH and VL domains having amino acid sequences as respectively shown in residues 20-135 of SEQ ID NO:

1 and residues 21-140 of SEQ ID NO;

2, or a chimeric or humanized form thereof, and wherein the cytotoxic agent is vcMMAE.

12. A pharmaceutical composition comprising the antibody drug conjugate of claim 11.