Compositions and methods for the diagnosis and treatment of tumor

Patent metadata

Field	Value
Publication number	US-RE47223-E
Application number	US-201514752767-A
Country	US
Kind code	E1
Filing date	Jun 26, 2015
Priority date	Jun 20, 2005
Publication date	Feb 5, 2019
Grant date	Feb 5, 2019

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.

First claim

What is claimed is:

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

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.

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 isolated antibody that specifically binds a TAT10772 polypeptide, said antibody comprising three light chain hypervariable regions (HVR-L1, HVR-L2 and 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 SEQ ID NO: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 SEQ ID NO:125; and
(f) HVR-H3 comprises the amino acid sequence of SEQ ID NO:183;
L is a linker;
D is a toxin drug moiety an auristatin; 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 3 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, and 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.

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 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 is sequence shown as SEQ ID NO:208.

31. An antibody drug conjugate comprising an antibody (Ab) covalently attached by a linker (L) to one or more toxin drug moieties (D), the compound having the formula:
Ab-(L-D)p or a pharmaceutically acceptable salt or solvate thereof, wherein:
Ab is an isolated antibody comprising the VH sequence shown in SEQ ID NO:208 and the VL sequence shown as SEQ ID NO:211;
L is a linker;
D is an auristatin; and
p is 1 to about 20.

32. The antibody drug conjugate of claim 31, wherein said conjugate is selected from the group consisting of Ab-MC-val-cit-PAB-MMAE, Ab-MC-val-cit-PAB-MMAF, Ab-MC-MMAE, and Ab-MC-MMAF.

33. The antibody drug conjugate of claim 32 wherein said conjugate is Ab-MC-val-cit-PAB-MMAE.

34. The antibody drug conjugate of claim 3 wherein said conjugate is Ab-MC-val-cit-PAB-MMAE.

35. The antibody drug conjugate of claim 3, wherein said auristatin is MMAE.

36. The antibody drug conjugate of claim 31, wherein said auristatin is MMAE.

Assignees

• Genentech Inc

Inventors

• Dennis Mark S
• Polakis Paul
• Mallet William

Classifications

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• G01N33/5756

  involving tumour-associated glycolinkage [TAG] · CPC title

• C07K2317/77

  Internalization into the cell · CPC title

• C07K2317/55

  Fab or Fab' · CPC title

• A61K2039/505

  comprising antibodies · CPC title