Antibodies to integrin AVB6 and use of same to treat cancer

Patent metadata

Field	Value
Publication number	US-9493566-B2
Application number	US-201314378746-A
Country	US
Kind code	B2
Filing date	Feb 14, 2013
Priority date	Feb 17, 2012
Publication date	Nov 15, 2016
Grant date	Nov 15, 2016

Abstract

The invention provides antibodies that specifically bind to integrin αvβ6. The antibodies are useful for treatment and diagnoses of various cancers as well as detecting αvβ6.

First claim

What is claimed is:

1. An isolated murine 15H3 monoclonal antibody that specifically binds integrin αvβ6 wherein the antibody comprises a heavy chain variable region comprising the sequence set forth in SEQ ID NO:1 and a light chain variable region comprising the sequence set forth in SEQ ID NO:2; and chimeric or humanized forms thereof.

2. An isolated monoclonal antibody that specifically binds integrin αvβ6 comprising heavy chain complementary determining region (CDR) sequences as set forth in SEQ ID NO:3 (CDR1), SEQ ID NO:4 (CDR2), and SEQ ID NO:5 (CDR3), and light chain CDR sequences as set forth in SEQ ID NO:6 (CDR4), SEQ ID NO:7 (CDR5), and SEQ ID NO:8 (CDR6).

3. A humanized antibody that specifically binds integrin αvβ6 having the heavy chain variable region having the amino acid sequence set forth in HB (SEQ ID NO:11) and a light chain variable region having the amino acid sequence set forth in LA (SEQ ID NO:10), LB (SEQ ID NO:24), LC (SEQ ID NO:25), LD (SEQ ID NO:26), LE (SEQ ID NO:27), LF (SEQ ID NO:28) or LG (SEQ ID NO:29); having the heavy chain variable region having the amino acid sequence set forth in HT (SEQ ID NO:22) and a light chain variable region having the amino acid sequence set forth in LA (SEQ ID NO:10), LB (SEQ ID NO:24), LC (SEQ ID NO:25), LD (SEQ ID NO:26), LE (SEQ ID NO:27), LF (SEQ ID NO:28) or LG (SEQ ID NO:29); having the heavy chain variable region having the amino acid sequence set forth in HL (SEQ ID NO:15) and a light chain variable region having the amino acid sequence set forth in LA (SEQ ID NO:10), LB (SEQ ID NO:24), LC (SEQ ID NO:25), LD (SEQ ID NO:26), LE (SEQ ID NO:27), LF (SEQ ID NO:28) or LG (SEQ ID NO:29); having the heavy chain variable region having the amino acid sequence set forth in HU (SEQ ID NO:23) and a light chain variable region having the amino acid sequence set forth in LA (SEQ ID NO:10), LB (SEQ ID NO:24), LC (SEQ ID NO:25), LD (SEQ ID NO:26), LE (SEQ ID NO:27), LF (SEQ ID NO:28) or LG (SEQ ID NO:29); having the heavy chain variable region having the amino acid sequence set forth in HN (SEQ ID NO:17) and a light chain variable region having the amino acid sequence set forth in LA (SEQ ID NO:10), LB (SEQ ID NO:24), LC (SEQ ID NO:25), LD (SEQ ID NO:26), LE (SEQ ID NO:27), LF (SEQ ID NO:28) or LG (SEQ ID NO:29) or having the heavy chain variable region having the amino acid sequence set forth in HM (SEQ ID NO:16) and a light chain variable region having the amino acid sequence set forth in LA (SEQ ID NO:10), LB (SEQ ID NO:24), LC (SEQ ID NO:25), LD (SEQ ID NO:26), LE (SEQ ID NO:27), LF (SEQ ID NO:28) or LG (SEQ ID NO:29).

4. The antibody of claim 1 wherein the antibody is an antigen binding fragment.

5. The antibody of claim 1 , wherein the heavy chain variable region is fused to a human heavy chain constant region and the light chain variable region is fused to a human light chain constant region.

6. The antibody of claim 5 , wherein the heavy chain constant region is a mutant form of natural human constant region which has reduced binding to an Fcgamma receptor relative to the natural human constant region.

7. The antibody of claim 5 , wherein the heavy chain constant region is of IgG1 isotype.

8. The antibody of claim 1 , wherein the antibody is conjugated to a cytotoxic agent.

9. The antibody of claim 1 , wherein the antibody is a chimeric form of the murine 15H3 antibody and comprises the heavy chain variable region comprising the sequence set forth in SEQ ID NO:1 fused to a human heavy chain constant region, and the light chain variable region comprising the sequence set forth in SEQ ID NO:2 fused to a human light chain constant region.

10. The antibody of claim 1 that is purified.

11. A pharmaceutical composition an antibody of claim 1 wherein comprising the antibody is a chimeric or humanized antibody.

12. An isolated nucleic acid encoding a heavy chain variable region and a light chain variable region as defined in claim 1 .

13. A method of treating a patient having pancreatic cancer or head and neck cancer, comprising administering to the patient an effective regime of an antibody of claim 8 wherein the antibody is a chimeric, human, or humanized antibody.

Assignees

• Seattle Genetics Inc

Inventors

• Ryan Maureen
• Django Sussman

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/6849

  the antibody targeting a receptor, a cell surface antigen or a cell surface determinant · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K19/00

  Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes} · CPC title

• A61K2039/505

  comprising antibodies · CPC title