Anti-zB7H6 antibody-drug conjugates

• US 7,858,759 B2
• Filed: 10/06/2008
• Issued: 12/28/2010
• Est. Priority Date: 10/04/2007
• Status: Active Grant

• Current Assignee: Zymogenetics Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Zymogenetics Incorporated (Bristol-Myers Squibb Company)
• Inventors: Kennedy, Jacob J., Brandt, Cameron S., Yi, Eugene C., Fox, Brian A., Xu, Wenfeng, Gao, Zeren
• Primary Examiner(s): OUSPENSKI, ILIA I
• Application Number:
  US12/246,214
• Publication Number:
  US 20090220502A1
• Time in Patent Office: 813 Days
• Field of Search: None
• US Class Current: 530/391.7
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 47/6851 the antibody targeting a determinant of a tumour cell
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/70532 B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 16/2827 against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/30 characterized by aspects of specificity or valency
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: G01N 2333/705 Assays involving receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: G01N 2500/02 Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
• CPC Class Codes: G01N 33/5011 for testing antineoplastic activity

Abstract

Disclosed is a newly identified B7 family member, zB7H6, which functions as a counter-receptor for the NK cell triggering receptor, NKp30. Methods and compositions for modulating NKp30-mediated NK cell activity based on the interaction of zB7H6 with NKp30, as well as related screening methods, are also disclosed. Further disclosed are anti-zB7H6 antibodies as well as antibody-drug conjugates comprising an anti-zB7H6 antibody conjugated to a therapeutic agent, including methods for using such antibodies and antibody-drug conjugates to exert therapeutic effects against zB7H6-expressing cells.

Claims

1. An antibody-drug conjugate comprising:

an antibody that specifically binds to a polypeptide segment consisting of the amino acid sequence set forth in residues 25-266 of SEQ ID NO;

2, wherein said antibody is conjugated to a cytotoxic agent selected from the group consisting of an anti-tubulin agent, a DNA minor groove binding agent, a DNA minor groove alkylating agent, a duocarmycin, and a puromycin.

2. The antibody-drug conjugate of claim 1, wherein the antibody is a monoclonal antibody.

3. The antibody-drug conjugate of claim 2, wherein the antibody is a human or humanized monoclonal antibody.

4. The antibody-drug conjugate of claim 2, wherein the antibody is a single chain antibody.

5. The antibody-drug conjugate of claim 1, wherein the anti-tubulin agent is selected from the group consisting of a dolastatin, a vinca alkaloid, a podophyllatoxin, a taxane, a baccatin derivative, a cryptophysin, a maytansinoid, and a combretastatin.

6. The antibody-drug conjugate of claim 1, wherein the antibody is conjugated to the cytotoxic agent via a linker.