Humanized antibodies to LIV-1 and use of same to treat cancer

Patent metadata

Field	Value
Publication number	US-9228026-B2
Application number	US-201113990778-A
Country	US
Kind code	B2
Filing date	Dec 6, 2011
Priority date	Dec 6, 2010
Publication date	Jan 5, 2016
Grant date	Jan 5, 2016

Abstract

The invention provides humanized antibodies that specifically bind to LIV-1. The antibodies are useful for treatment and diagnoses of various cancers as well as detecting LIV-1.

First claim

What is claimed is:

1. A humanized antibody, that specifically binds human LIV-1 comprising a mature heavy chain variable region comprising three CDRs of SEQ ID NO:53 and having an amino acid sequence at least 95% identical to SEQ ID NO:53 provided that position H27 is occupied by L, position H29 is occupied by I, H30 by E and H94 by V and a mature light chain variable region comprising three CDRs of SEQ ID NO:60 at least 95% identical to SEQ ID NO:60 provided position L36 is occupied by Y and position L46 by P.

2. The humanized antibody of claim 1 , further provided position H76 is occupied by N.

3. The humanized antibody of claim 1 wherein the mature heavy chain variable region is fused to a heavy chain constant region and the mature light chain variable region is fused to a light chain constant region.

4. The humanized antibody of claim 3 , wherein the heavy chain constant region is a mutant form of a natural human constant region which has reduced binding to an Fcgamma receptor relative to the natural human constant region.

5. The humanized antibody of claim 3 , wherein the heavy chain constant region is of IgG1 isotype.

6. The humanized antibody of claim 3 , wherein the heavy chain constant region has an amino acid sequence comprising SEQ ID NO:44 and the light chain constant region has an amino acid sequence comprising SEQ ID NO:42.

7. The humanized antibody of claim 3 , wherein the heavy chain constant region has an amino acid sequence comprising SEQ ID NO:46 (S239C) and the light chain constant region has an amino acid sequence comprising SEQ ID NO:42.

8. The humanized antibody of claim 1 , wherein the mature heavy chain variable region has an amino acid sequence designated SEQ ID NO:52 or 53 and the mature light chain variable region has an amino acid sequence designated SEQ ID NO: 59 or 60.

9. The humanized antibody of claim 1 , wherein the mature heavy chain variable region has an amino acid sequence designated SEQ ID NO:53 and the mature light chain variable region has an amino acid sequence designated SEQ ID NO:60.

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

11. The humanized antibody of claim 1 , having an association constant for human or cynomolgus monkey LIV-1 of 0.5 to 2×10 9 M −1 .

12. A nucleic acid encoding a mature heavy chain variable region and/or a mature light chain variable region as defined by claim 1 .

13. A method of treating a patient having a cancer expressing LIV-1, comprising administering to the patient an effective regime of a humanized antibody of claim 1 .

14. The method of claim 13 , wherein the cancer is a breast cancer, a prostate cancer, a cervical cancer or a melanoma.

15. A pharmaceutical composition comprising a humanized antibody of claim 1 .

16. The method of claim 13 , wherein the antibody is conjugated to a cytotoxic or cytostatic agent.

17. The method of claim 13 , wherein the isotype of the antibody is human IgG1.

Assignees

• Smith Maria Leia
• Sussman Django
• Arthur William
• Nesterova Albina
• Seattle Genetics Inc

Inventors

• Smith Maria Leia
• Sussman Django
• Arthur William
• Nesterova Albina

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title

• A61P15/00

  Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives · CPC title

• A61P13/08

  of the prostate · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title