Compositions and diagnostic techniques for tumour and methods of treating it

FIELD: medicine.

SUBSTANCE: invention refers to immunology and biotechnology. What is offered is a TAT 10772 antibody which is characterised by the presence of six CDR. What is described is a method for identifying the antibody which binds TAT 10772 polypeptide. What is disclosed is using the antibody according to claim 1 for TAT 10772 expressing cell growth inhibition, and for therapeutic treatment of a tumour in a mammal where the tumour expresses TAT 10772. There are described: a presence-absence test of TAT 10772 protein in a sample which is supposed to contain it, and a method of diagnostic detection of a TAT 10772 expressing tumour, based on using the antibody according to claim 1.

EFFECT: presented inventions can find further application in therapy and diagnostics of TAT 10772 expressing tumours.

31 cl, 37 dwg, 11 tbl, 18 ex

 

The text descriptions are given in facsimile form.

1. The selected antibody that contains three hypervariable region of the light chain (HVR-L1=SEQ ID NO:14, HVR-L2=SEQ ID NO:35 and HVR-L3 is SEQ ID NO:59) and three hypervariable region of the heavy chain (HVR-H1=SEQ ID NO:74, HVR-H2=SEQ ID NO:94 and HVR-H3=SEQ ID NO:113), where
(a) sequence HVR-L1 can be replaced by one of the sequences represented by SEQ ID NO:15-34;
(b) sequence HVR-L2 can be replaced by one of the sequences represented by SEQ ID NO:36-58;
(C) sequence HVR-L3 may be replaced by one of the sequences presented in SEQ ID NO:60-73;
(g) a sequence of HVR-H1 can be replaced by one of the sequences presented in SEQ ID NO:74-93;
(d) sequence HVR-H2 can be replaced by one of the sequences presented in SEQ ID NO:95-112; and
(e) sequence HVR-H3 may be replaced by one of the sequences presented in SEQ ID NO:114-118, where the specified antibody binds to the polypeptide having SEQ ID NO:2.

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 sequence is, presented in SEQ ID NO:194-197.

4. 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, 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, represents a fragment of the antibody.

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

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

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

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

10. The antibody of claim 8, in which the cytotoxic agent is a toxin.

11. The antibody of claim 10, in which the toxin is selected from the group comprising maytansinoid and calicheamicin.

12. The antibody of claim 10, in which the toxin is maytansinoid.

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

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

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

16. Antibody pop, where the cell is a cancer cell of the ovary.

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

18. The manner of identification of an antibody that binds to the polypeptide having SEQ ID NO:2, and the second antibody, where the second antibody is an antibody according to claim 1, namely, that determine the capacity of the first antibody to block the binding of the second antibody, with the polypeptide having SEQ ID NO:2, where the first ability of antibodies to block the binding of the second antibody, with the polypeptide having SEQ ID NO:2 is at least 40%, and when using the same concentration of antibodies indicates that the first antibody has the ability to contact the epitope is associated with the second the antibody.

19. The use of antibodies according to claim 1 for inhibiting growth of cells that expresses a protein having the amino acid sequence represented in SEQ ID NO:2.

20. The application of claim 19, in which the cell is a cancer cell of the ovary.

21. The application of claim 19, in which the indicated antibody conjugated with a cytotoxic agent.

22. The use of antibodies according to claim 1 for therapeutic treatment of a mammal, which has a malignant tumor containing cells that Express a protein having the amino acid sequence of which is presented in SEQ IDNO:2.

23. The application of article 22, in which a malignant tumor is a tumor of the ovary.

24. The application of article 22, in which the indicated antibody conjugated with a cytotoxic agent.

25. The method of determining the presence of TAT protein 10772 in the sample, which assumes the presence of a specified protein, which consists in the fact that the treated sample with an antibody according to claim 1 and determine the binding of an antibody to the polypeptide having SEQ ID NO:2, where the binding of an antibody to the specified polypeptide indicates the presence of the indicated protein in the sample.

26. The method according A.25, in which the sample contains a cell, which is expected expresses this protein.

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

28. The method according to item 27, in which the antibody carries a detectable label.

29. The diagnostic method of identifying a tumor that expresses TAT 10772 antigen, namely, that bring into contact a test sample of tissue cells obtained from the body of the mammal with an antibody according to claim 1, and reveal the formation of a complex between the antibody and the polypeptide having SEQ ID NO:2, in the test sample, where the formation of the complex indicates the presence of tumor in the body of a mammal.

30. The method according to item 27, in which the test sample of tissue cells obtained from the organism of the individual, is vtorogo assumes the presence of a malignant tumor.

31. The method according to p in which a malignant tumor is a tumor of the ovary, breast or pancreas.



 

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27 cl, 19 dwg, 8 tbl, 18 ex

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24 cl, 41 dwg, 1 tbl, 26 ex

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FIELD: medicine, pharmaceutics.

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19 cl, 7 tbl, 23 ex

FIELD: medicine.

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26 cl, 26 dwg, 9 ex

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29 cl, 15 dwg, 6 tbl, 9 ex

FIELD: medicine.

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14 cl, 44 dwg, 4 ex

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6 cl, 5 dwg, 2 tbl, 8 ex

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9 cl, 20 dwg, 7 tbl, 23 ex

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7 cl, 12 dwg, 1 tbl, 3 ex

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41 cl, 45 dwg, 11 tbl, 18 ex

FIELD: medicine.

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32 cl, 3 tbl, 6 ex

FIELD: medicine.

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44 cl, 45 dwg, 8 ex

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16 cl, 4 dwg, 1 tbl, 13 ex

FIELD: medicine.

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2 cl, 8 dwg, 1 tbl, 2 ex

FIELD: medicine.

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4 cl, 6 dwg, 22 tbl, 19 ex

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10 cl, 21 dwg, 11 ex

FIELD: medicine.

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23 cl, 4 dwg, 5 tbl, 15 ex

FIELD: immunology, antibodies.

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11 cl, 8 dwg, 2 tbl, 13 ex

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67 cl, 11 dwg, 1 tbl, 11 ex

FIELD: medicine.

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5 cl, 4 tbl, 7 ex

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