Compositions and methods for the diagnosis and treatment of tumor

• US 7,989,595 B2
• Filed: 06/14/2006
• Issued: 08/02/2011
• Est. Priority Date: 06/20/2005
• Status: Expired

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Mallet, William, Polakis, Paul, Dennis, Mark S.
• Primary Examiner(s): GUSSOW, ANNE
• Application Number:
  US11/452,990
• Publication Number:
  US 20090041749A1
• Time in Patent Office: 1,875 Days
• Field of Search: None
• US Class Current: 530/388.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/4025 not condensed and containing further heterocyclic rings, e.g. cromakalim
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/537 spiro-condensed or forming part of bridged ring systems
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 38/07 Tetrapeptides
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/6803 Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
• CPC Class Codes: A61K 47/68031 the drug being an auristatin
• CPC Class Codes: A61K 47/68033 the drug being a maytansine
• CPC Class Codes: A61K 47/6817 Toxins
• CPC Class Codes: A61K 47/6835 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
• CPC Class Codes: A61K 47/6851 the antibody targeting a determinant of a tumour cell
• CPC Class Codes: A61P 1/18 : for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 : Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 15/00 : Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: C07K 16/3015 : Breast
• CPC Class Codes: C07K 16/303 : Liver or Pancreas
• CPC Class Codes: C07K 16/3069 : Reproductive system, e.g. ovaria, uterus, testes, prostate
• CPC Class Codes: C07K 16/3092 : against tumour-associated mucins
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/55 : Fab or Fab'
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: Y10T 428/13 : Hollow or container type article [e.g., tube, vase, etc.]

Abstract

The present invention is directed to compositions of matter useful for the diagnosis and treatment of tumor in mammals and to methods of using those compositions of matter for the same.

Claims

1. A monoclonal antibody produced by the hybridoma cell 3A5.3 that binds to a TAT10772 polypeptide.

3. An antibody drug conjugate comprising an antibody covalently attached by a linker to one or more toxin drug moieties, the compound having the formula:

Ab-(L-D)p

or a pharmaceutically acceptable salt or solvate thereof, wherein;

Ab is an antibody according to claim 1 or 2;

L is a linker;

D is a toxin drug moiety; and

p is 1 to about 20.

4. The antibody drug conjugate of claim 3 wherein Ab is a humanized 3A5.3 antibody.

5. The antibody drug conjugate of claim 3 wherein D is a maytansinoid.

6. The antibody drug conjugate of claim 5 wherein the maytansinoid is DM1.

7. The antibody drug conjugate of claim 3 wherein D is an auristatin.

8. The antibody drug conjugate of claim 7 wherein the auristatin is MMAE or MMAF.

9. The antibody drug conjugate of claim 3 wherein L is MC-val-cit-PAB or MC.

10. The antibody drug conjugate of claim 3 wherein L is SMCC, SPP, or BMPEO.

11. The antibody drug conjugate of claim 3 selected from the formula:

Ab-MC-val-cit-PAB-MMAE, Ab-MC-val-cit-PAB-MMAF, Ab-MC-MMAE, Ab-MC-MMAF, Ab-SPP-DM1, and Ab-SMCC-DM1.

12. The antibody drug conjugate compound of claim 3 wherein the antibody is attached to the linker through a cysteine thiol of the antibody.

13. A pharmaceutical formulation comprising the antibody drug conjugate of claim 3, and a pharmaceutically acceptable diluent, carrier or excipient.

14. The pharmaceutical formulation of claim 13 further comprising a therapeutically effective amount of a chemotherapeutic agent selected from letrozole, oxaliplatin, doxetaxel, 5-FU, leucovorin, lapatinib, and gemcitabine.

15. An article of manufacture comprising

an antibody-drug conjugate compound of claim 3;

a container; and

a package insert or label indicating that the compound can be used to treat cancer characterized by the overexpression of a TAT10772 polypeptide.

16. The article of manufacture of claim 15 wherein the cancer is prostate cancer, cancer of the urinary tract, pancreatic cancer, lung cancer, breast cancer, colon cancer or ovarian cancer.

2. An isolated antibody that specifically binds a TAT10772 polypeptide, said antibody comprising three light chain hypervariable regions (HVR-L1, HVR-L2and HVR-L3) and three heavy chain hypervariable regions (HVR-H1, HVR-H2 and HVR-H3) wherein:

(a) HVR-L1 comprises the amino acid sequence of SEQ ID NO;

119;

(b) HVR-L2 comprises the amino acid sequence of any one of SEQ ID NOS;

120-121;

(c) HVR-L3 comprises the amino acid sequence of SEQ ID NO;

122;

(d) HVR-H1 comprises the amino acid sequence of SEQ ID NO;

123;

(e) HVR-H2 comprises the amino acid sequence of any one of SEQ ID NOS;

124-127; and

(f) HVR-H3 comprises the amino acid sequence of any one of SEQ ID NOS;

128-183.

17. The antibody of claim 2 which is an antibody fragment.

18. The antibody of claim 2 which is a chimeric or a humanized antibody.

19. The antibody of claim 2 which is conjugated to a growth inhibitory agent.

20. The antibody of claim 2 which is conjugated to a cytotoxic agent.

21. The antibody of claim 20, wherein the cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes.

22. The antibody of claim 20, wherein the cytotoxic agent is a toxin.

23. The antibody of claim 22, wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin.

24. The antibody of claim 22, wherein the toxin is a maytansinoid.

25. The antibody of claim 2 which is produced in bacteria.

26. The antibody of claim 2 which is produced in CHO cells.

27. The antibody of claim 2 which induces death of a cell to which it binds.

28. The antibody of claim 27, wherein said cell is an ovarian cancer cell.

29. The antibody of claim 2 which is detectably labeled.

30. The antibody of claim 2 that comprises the VH sequence shown as SEQ ID NO:

208.