Compositions and diagnostic technique for tumour

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology, and represents an antibody able to bind a tumour-associated antigen TAT 10772 polypeptide. Besides, there are presented antibody conjugate with a drug, pharmaceutical composition, method of cell proliferation inhibition, method of treating the TAT 10772 expressing tumours , analysis for tumour cell detection, as well as kit for treating the tumours.

EFFECT: invention can be used in treating the tumours expressing the tumour associated antigen TAT 10772 polypeptide.

41 cl, 45 dwg, 11 tbl, 18 ex

 

The text descriptions are given in facsimile form.

1. The selected antibody can bind TAT 10772 and contains three hypervariable region of the light chain (HVR-L1, HVR-L2 and HVR-L3) and three hypervariable region of the heavy chain (HVR-H1, HVR-H2 and HVR - H3) or antigennegative fragment, where:
(a) HVR-L1 comprises the amino acid sequence represented in SEQ ID NO:119;
(b) HVR-L2 comprises amino acid sequence selected from the sequences represented by SEQ ID NO:120-121;
(C) HVR-L3 comprises the amino acid sequence represented in SEQ ID NO:122;
(d) HVR-H1 comprises the amino acid sequence represented in SEQ ID NO:123;
(e) HVR-H2 comprises the amino acid sequence selected from the presented in SEQ ID NO:124-127; and (f) HVR-H3 comprises the amino acid sequence selected from the presented in SEQ ID NO:128-183.

2. The selected antibody according to claim 1, further containing a sequence of the acceptor human consensus wireframe plot VH selected from one of the sequences presented in SEQ ID NO:184-193.

3. The selected antibody according to claim 1, further containing a sequence of the acceptor human consensus frame section VL selected from one of the sequences presented in SEQ ID NO:194-197.

4. The selected antibody according to claim 1, additionally containing p is the sequence of the acceptor human consensus wireframe plot VH, selected from one of the sequences presented in SEQ ID NO:184-193, and the sequence of the acceptor human consensus frame section VL selected from one of the sequences presented in SEQ ID NO:194-197.

5. The antibody according to claim 1, which represents a chimeric or humanitariannet antibody.

6. The antibody of claim 1 conjugated with inhibiting the growth of the agent.

7. The antibody of claim 1 conjugated with a cytotoxic agent.

8. The antibody according to claim 7, in which the cytotoxic agent is selected from the group including toxins, antibiotics, radioactive isotopes or nucleotidase enzymes.

9. The antibody according to claim 7, in which the cytotoxic agent is a toxin.

10. The antibody according to claim 9, in which the toxin is selected from the group comprising maytansinoid and calicheamicin.

11. The antibody according to claim 9, in which the toxin is maytansinoid.

12. The antibody according to claim 1, which is produced in bacteria.

13. The antibody according to claim 1, which is produced in Cho-cells.

14. The antibody according to claim 1, which induces death of cells with which it is associated.

15. The antibody according to 14, where the cell is a cancer cell of the ovary.

16. The antibody according to claim 1, which is detectable label.

17. The antibody according to clause 16, which comprises the VH sequence shown in SEQ ID NO:208.

18. The antibody according to item 16, which is before the sequence VL, shown in SEQ ID NO:211.

19. The antibody according to clause 16, which comprises the VH sequence shown in SEQ ID NO:208, and the VL sequence shown in SEQ ID NO:211.

20. Conjugate antibody with a drug, comprising an antibody covalently attached by a linker to one or more particles of the medicinal product, representing the toxin, where the compound has the formula
Ab-(L-D)p
or its pharmaceutically acceptable salt, where
AB is an antibody according to claim 1,
L is a linker,
D - particle medicines, representing the toxin, and
p is from 1 to 20.

21. Conjugate antibodies with drug in claim 20, where AB represents A or 11D 10.

22. Conjugate antibodies with drug in claim 20, where D is maytansinoids.

23. Conjugate antibodies with drug and 22, where maytansinoid is DM1.

24. Conjugate antibodies with drug in claim 20, where D is auristatin.

25. Conjugate antibody with a drug under paragraph 24, where auristatin is MMAE or MMAF.

26. Conjugate antibodies with drug in claim 20, where L is the MC-val-cit-PAB or MILLISECONDS.

27. Conjugate antibodies with drug in claim 20, where L is the SMCC, SPP or UMRAO.

28. Conjugate antibodies with drug in claim 20, selected is of the formula Ab-MC-val-cit-PAB-MMAE, Ab-MC-val-cit-PAB-MMAF, Ab-MS-MMAE, Ab-MC-MMAF, Ab-SPP-DM1 and Ab-SMCC-DM1.

29. Conjugate antibodies with drug on p, where AB represents A or 11D 10.

30. Conjugate antibodies with drug in claim 20, where the antibody is attached to the linker through cysteinyl antibodies.

31. The pharmaceutical composition intended for the treatment of tumors expressing TAT 10772, and comprising a conjugate of the antibody with the drug in claim 20 and a pharmaceutically acceptable solvent, carrier or excipient.

32. The pharmaceutical composition according to p, optionally containing a therapeutically effective amount of chemotherapeutic agent selected from letrozole, oxiplatin, docetaxel, 5-FU, leucovorin, lapatinib and gemcitabine.

33. Method of inhibiting cell proliferation, comprising the treatment of tumor cells of a mammal expressing TAT 10772, in cell culture medium conjugate antibodies with drug on item 21, in which the proliferation of tumor cells is inhibited.

34. The method according to p, in which the cell is a cancer cell of the ovary.

35. A method of treatment of tumors expressing THAT, providing for the introduction to the patient the pharmaceutical composition according to p.

36. The method according to p, in which the tumor is selected from the group comprising prostate cancer, cancer of the urinary put the th, pancreatic cancer, lung cancer, breast cancer, colon cancer and ovarian cancer.

37. The method according to p, wherein the patient is administered a chemotherapeutic agent in combination with a conjugate of an antibody with a drug, where the chemotherapeutic agent is selected from the group including letrozole, oxiplatin, docetaxel, 5-FU, leucovorin, lapatinib and gemcitabine.

38. Analysis for the detection of tumor cells, including:
(a) treatment of the cells with a conjugate of the antibody with the drug in item 21; and
(b) determining the amount of binding of the conjugate antibody with a drug from the cell.

39. The analysis in 38, in which the cell is a cancer cell of the prostate, pancreas, lung, breast, colon and ovary.

40. Set includes
conjugate antibodies with drug on item 21;
container; and
a package insert or label, which indicates that the connection can be used to treat tumors, characterized by sverkhekspressiya associated with tumor functionally active polypeptide comprising the amino acid sequence that is 80% identical to the amino acid sequence of SEQ ID NO:2.

41. Set p, where the tumor is selected from the group comprising cancer, prostate cancer, urinary tract cancer, pancreatic cancer, lung cancer, breast cancer, the AK colon and ovarian cancer.



 

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