KIR3DL2 binding agents

Patent metadata

Field	Value
Publication number	US-10246510-B2
Application number	US-201314429416-A
Country	US
Kind code	B2
Filing date	Sep 17, 2013
Priority date	Sep 19, 2012
Publication date	Apr 2, 2019
Grant date	Apr 2, 2019

Abstract

The present invention relates to methods for the treatment of cancer and inflammatory disease using antibodies (e.g. monoclonal antibodies), antibody fragments, and derivatives thereof that specifically bind KIR3DL2. The invention also relates to antibodies, cells producing such antibodies; methods of making such antibodies; fragments, variants, and derivatives of the antibodies; pharmaceutical compositions comprising the same.

First claim

The invention claimed is:

1. An isolated monoclonal antibody selected from the group consisting of:
(a) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 4 (HCDR1), SEQ ID NO: 7 (HCDR2) and SEQ ID NO: 9 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 10, 11 and 12, respectively;
(b) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 15 (HCDR1), SEQ ID NO: 18 (HCDR2) and SEQ ID NO: 20 (HCDR3) respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 21, 22 and 23, respectively;
(c) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 16 (HCDR1), SEQ ID NO: 18 (HCDR2) and SEQ ID NO: 28 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 29, 30 and 31, respectively;
(d) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 26 (HCDR1), SEQ ID NO: 36 (HCDR2) and SEQ ID NO: 38 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 39, 40 and 41, respectively;
(e) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 16 (HCDR1), SEQ ID NO: 36 (HCDR2) and SEQ ID NO: 38 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 44, 45 and 41, respectively; and
(f) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 48 (HCDR1), SEQ ID NO: 51 (HCDR2) and SEQ ID NO: 53 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 54, 55 and 56, respectively.

2. The antibody of claim 1 , wherein said antibody has reduced binding to a mutant KIR3DL2 polypeptide comprising a mutation at residues V178 and P179, a mutant KIR3DL2 polypeptide comprising a mutation at residues H180 and S181, and/or a mutant KIR3DL2 polypeptide comprising a mutation at residues E130, H131 and R145, relative to binding between the antibody and a wild-type KIR3DL2 polypeptide of SEQ ID NO: 1.

3. The antibody of claim 1 , wherein said antibody comprises a human IgG heavy chain constant region.

4. The antibody of claim 1 , wherein said antibody is a chimeric, human or humanized antibody.

5. The antibody of claim 1 , wherein said antibody is conjugated or covalently bound to a toxic agent.

6. A pharmaceutical composition comprising an antibody of claim 1 , and a pharmaceutically acceptable carrier.

7. A method for the treatment of a KIR3DL2-expressing CD4+ T cell cancer in a patient in need thereof, the method comprising administering to said patient an effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a monoclonal antibody selected from the group consisting of:
(a) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 4 (HCDR1), SEQ ID NO: 7 (HCDR2) and SEQ ID NO: 9 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 10, 11 and 12, respectively;
(b) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 15 (HCDR1), SEQ ID NO: 18 (HCDR2) and SEQ ID NO: 20 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 21, 22 and 23, respectively;
(c) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 16 (HCDR1), SEQ ID NO: 18 (HCDR2) and SEQ ID NO: 28 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 29, 30 and 31, respectively;
(d) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 26 (HCDR1), SEQ ID NO: 36 (HCDR2) and SEQ ID NO: 38 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 39, 40 and 41, respectively;
(e) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 16 (HCDR1), SEQ ID NO: 36 (HCDR2) and SEQ ID NO: 38 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 44, 45 and 41, respectively; and
(f) a monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 48 (HCDR1), SEQ ID NO: 51 (HCDR2) and SEQ ID NO: 53 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 54, 55 and 56, respectively.

8. The method of claim 7 , wherein said cancer is selected from Mycosis fungoides and Sézary Syndrome.

9. The method of claim 7 , said monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 4 (HCDR1), SEQ ID NO: 7 (HCDR2) and SEQ ID NO: 9 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 10, 11 and 12, respectively.

10. The method of claim 7 , said monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 15 (HCDR1), SEQ ID NO: 18 (HCDR2) and SEQ ID NO: 20 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 21, 22 and 23, respectively.

11. The method of claim 7 , said monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 16 (HCDR1), SEQ ID NO: 18 (HCDR2) and SEQ ID NO: 28 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 29, 30 and 31, respectively.

12. The method of claim 7 , said monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 26 (HCDR1), SEQ ID NO: 36 (HCDR2) and SEQ ID NO: 38 (HCDR3), respectively, and (ii) a 7 light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 39, 40 and 41, respectively.

13. The method of claim 7 , said monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 16 (HCDR1), SEQ ID NO: 36 (HCDR2) and SEQ ID NO: 38 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a sequence of SEQ ID NO: 44, 45 and 41, respectively.

14. The method of claim 7 , said monoclonal antibody having (i) a heavy chain comprising CDR 1, 2 and 3 (HCDR1, HCDR2, HCDR3) comprising a sequence of SEQ ID NO: 48 (HCDR1), SEQ ID NO: 51 (HCDR2) and SEQ ID NO: 53 (HCDR3), respectively, and (ii) a light chain comprising CDR 1, 2 and 3 (LCDR1, LCDR2, LCDR3) comprising a s

Assignees

• Innate Pharma

Inventors

• Gauthier Laurent
• Rossi Benjamin
• Sicard Hélène
• Paturel Carine

Classifications

• G01N2800/7095

  Inflammation · CPC title

• A61K47/6849

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

• C07K2317/77

  Internalization into the cell · CPC title

• G01N33/56972

  White blood cells · CPC title

• G01N2800/7028

  Cancer · CPC title