New antiproliferative antibodies

FIELD: medicine, pharmaceutics.

SUBSTANCE: this invention relates to biotechnology and immunology. One proposes: JAM-A protein antibody or functional fragment thereof, hybridoma secreting such antibody, nucleic acid, expression vector and host cell as well as a method for the antibody and composition production. One considers application of the JAM-A protein antibody or functional fragment thereof.

EFFECT: invention usage ensures creation of new JAM-A protein antibodies which may be further applied in treatment or prevention of diseases related to proliferation of tumour cells extracting JAM-A protein.

34 cl, 31 dwg, 5 tbl, 19 ex

 

The text descriptions are given in facsimile form.

1. An isolated antibody or functional fragment can inhibit the proliferation of tumor cells expressing JAM-A, in vitro and/or in vivo, which is characterized in that it includes a CDR, it is matter of sequence SEQ ID No. 1, 2, 3, 4, 5 and 6.

2. The antibody or functional fragment according to claim 1, characterized in that it is a monoclonal antibody.

3. The antibody or functional fragment according to claim 1, characterized in that it comprises a heavy chain that contains the following three CDRs, respectively CDR-H1, CDR-H2 and CDR-H3, where:
CDR-H1 contains the sequence SEQ ID No. 2, 7, or 9;
CDR-H2 has the sequence SEQ ID No. 4 or 11; and
CDR-H3 has the sequence SEQ ID No. 6 or 12.

4. The antibody or functional fragment according to claim 1, characterized in that it comprises a heavy chain contains the CDR-H1 sequence of SEQ ID No. 7, CDR-H2 of the sequence SEQ ID No. 4 and CDR-H3 of the sequence SEQ ID No. 12.

5. The antibody or functional fragment according to claim 1, characterized in that it comprises a heavy chain contains the CDR-H1 sequence of SEQ ID No. 9, CDR-H2 of the sequence SEQ ID No. 11, and CDR-H3 of the sequence SEQ ID No. 6.

6. The antibody or functional fragment according to claim 1, characterized in that it comprises a light chain that contains the following three CDRs, respectively CDR - L1, CDR-L2 and CDR-L3, where:
CDR-L1 contains the sequence SEQ ID No. 1 or 8;
CDR-L2 contains the sequence SEQ ID No. 3 or 10; and
CDR-L3 contains the sequence SEQ ID No. 5.

7. The antibody or functional fragment according to claim 1, characterized in that it comprises a light chain, sod is readuy CDR-L1 of the sequence SEQ ID No. 1, CDR-L2 of the sequence SEQ ID No. 3 and CDR-L3 of the sequence SEQ ID No. 5.

8. The antibody or functional fragment according to claim 1, characterized in that it comprises a light chain contains the CDR-L1 of the sequence SEQ ID No. 8, CDR-L2 of the sequence SEQ ID No. 10 and CDR-L3 of the sequence SEQ ID No. 5.

9. The antibody or functional fragment according to claim 1, characterized in that it comprises a light chain that contains the following three CDRs:
CDR-L1 of the sequence SEQ ID No. 1;
CDR-L2 of the sequence SEQ ID No. 3; and
CDR-L3 of the sequence SEQ ID No. 5, and a heavy chain that contains the following three CDRs:
CDR-H1 sequence of SEQ ID No. 7;
CDR-H2 of the sequence SEQ ID No. 4; and
CDR-H3 of the sequence SEQ ID No. 12.

10. The antibody or functional fragment according to claim 1, characterized in that it comprises a light chain that contains the following three CDRs:
CDR-L1 of the sequence SEQ ID No. 8;
CDR-L2 of the sequence SEQ ID No. 10; and
CDR-L3 of the sequence SEQ ID No. 5, and a heavy chain that contains the following three CDRs:
CDR-H1 sequence of SEQ ID No. 9;
CDR-H2 of the sequence SEQ ID No. 11, and
CDR-H3 of the sequence SEQ ID No. 6.

11. The antibody or functional fragment according to claim 1, characterized in that it comprises the sequence of the variable domain of the light chain containing the amino acid sequence of SEQ ID No. 13, as well as the fact that it contains a follower of the awn variable domain of the heavy chain, containing the amino acid sequence of SEQ ID No. 14.

12. Humanitariannet antibody or functional fragment according to claim 1, characterized in that it comprises the sequence of the variable domain of the light chain containing the amino acid sequence of SEQ ID No. 17, and also that it contains the sequence of the variable domain of the heavy chain containing the amino acid sequence of SEQ ID No. 18 or 19.

13. The antibody or functional fragment according to claim 1, characterized in that the said functional fragment is selected among the fragments Fv, Fab, (Fab')2, Fab', scFv, scFv-Fc and dimeric antibodies or any fragment, the half-life of which is enlarged, such as Paglierani fragments.

14. The antibody or functional fragment according to claim 1, characterized in that said antibody is a murine antibody, and the fact that it comprises a light chain amino acid sequence SEQ ID No. 15 and a heavy chain amino acid sequence of SEQ ID No. 16.

15. The antibody or functional fragment according to claim 1, characterized in that said antibody is a chimeric antibody contains a constant region of the light chain and heavy chain derived from an antibody from a species heterologous mouse.

16. Chimeric antibody or functional fragment according to item 15, characterized is to be so, the specified heterologous species is man.

17. Humanitariannet antibody or functional fragment according to item 16, characterized in that the constant region of the light chain and heavy chain derived from a human antibody are lambda or Kappa and gamma-1, gamma-2 or gamma-4 regions, respectively.

18. Mouse hybridoma, secreting the antibody according to claim 1, registered in the National collection of microorganism cultures (CNCM, Institut Pasteur, Paris, France) under the number I-3646.

19. The antibody is able to inhibit the proliferation of tumor cells expressing JAM-A, in vitro and/or in vivo, which is characterized in that it includes a CDR having the sequence SEQ ID№1, 2, 3, 4, 5 and 6, Sekretareva hybridomas on p.

20. The antibody or functional fragment according to any one of claims 1 to 19 or 21, characterized in that it is specific to contact the protein JAM-A (connective adhesion molecule-A).

21. The antibody or functional fragment according to claim 20, characterized in that the Kd for the protein JAM-A is from about 1 nm to 1 PM, more preferably from 10 PM until 40 PM.

22. An isolated nucleic acid, characterized in that it is selected among the following nucleic acids:
a) nucleic acid, DNA or RNA) that encodes the antibody or the functional fragment is one which one of claims 1 to 17, and 19-21; and
b) a nucleic acid complementary to the nucleic acid defined in paragraph (a).

23. The expression vector for the expression of antibodies according to claim 1, containing a nucleic acid according to item 22.

24. A host cell containing a vector according to item 23.

25. A method of producing an antibody or functional fragment according to one of claims 1 to 17 and 19 to 21, characterized by the presence of the following stages:
a) culturing in the medium and culture conditions suitable for the host cell according to paragraph 24; and
b) the allocation thus obtained indicated antibody or one of its functional fragments from culture medium or from these cultured cells.

26. The antibody or functional fragment according to one of claims 1 to 17 and 19 to 21 for use as anticancer drugs.

27. The composition is capable of inhibiting the proliferation of tumor cells expressing JAM-A, containing as active ingredient a compound consisting of an antibody or functional fragment according to one of claims 1 to 17, 19 to 21 and 26 in an effective amount.

28. The composition according to item 27, characterized in that it as a combination product for use in simultaneous, separate or delayed form also contains anti-tumor antibody other than an antibody directed against the protein JAM-A.

29. The composition according to item 27, characterizes the jaś fact, it is as a combination product for use in simultaneous, separate or delayed form also contains a cytotoxic/cytostatic agent.

30. Composition according to one of PP-29 for use as a medicine.

31. The use of antibodies or functional fragment according to one of claims 1 to 17, 19 to 21 and 27, and/or composition according to any one of p-33 for the manufacture of drugs for the prevention or treatment of diseases associated with proliferation of tumor cells expressing JAM-A.

32. Use p for the manufacture of drugs for the prevention or treatment of cancer.

33. Use p, characterized in that said cancer is a cancer selected among prostate cancer, osteosarcoma, lung cancer, breast cancer, endometrial cancer, multiple myeloma, ovarian cancer, pancreatic cancer and colon cancer.

34. Use p, characterized in that said cancer is a cancer selected among estrogen-dependent breast cancer, lung cancer, colon cancer and pancreatic cancer.



 

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