Nucleotide sequences coding for variable regions of beta chains of human T lymphocyte receptors, corresponding peptide segments and the diagnostic and therapeutic uses

• US 20030068628A1
• Filed: 03/12/2002
• Published: 04/10/2003
• Est. Priority Date: 06/04/1990
• Status: Active Grant

• Current Assignee: Aventis Pharma SA (Sanofi )
• Original Assignee: Aventis Pharma SA (Sanofi )
• Inventors: Hercend, Thierry, Triebel, Frederic, Roman-Roman, Sergio, Ferradini, Laurent
• Granted Patent: US 7,294,712 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/2809 against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins

Abstract

The present invention relates to new nucleotide sequences coding for variable regions of β chains of human T lymphocyte receptors, corresponding peptide segments and the diagnostic and therapeutic uses.

Claims

1. Nucleotide sequences coding for the variable regions of β

chains of human T lymphocyte receptors, corresponding to cDNAs containing nucleotide sequences chosen from any one of the Vβ

segments corresponding to one of the sequences SEQ ID No. 2 to 19, and the sequences which differ from them by one or more nucleotides.

2. Sequences according to claim 1 coding for the variable regions of β

chains of human T lymphocyte receptors, corresponding to the cDNAs containing nucleotide sequences chosen from any one of the Vβ

segments corresponding to one of the sequences SEQ ID 2 to 5, and the sequences which differ from them by one or more nucleotides.

7. Peptides coded by any one of the nucleotide sequences as defined in any one of claims 1 to 6, as well as the alleles and the derivatives of the latter which possess the same function.

8. Expression vectors containing a DNA sequence coding for one of the peptides as defined in claim 7.

9. Hosts transformed with a vector according to claim 8.

10. Antibodies directed against an antigenic determinant of one of the peptides defined in claim 7.

11. Antibody according to claim 10 which is a monoclonal antibody or a fragment of the latter.

12. Fragment Fab, Fab′

or (Fab′

)₂ of a monoclonal antibody according to claim 11 and derivatives of the latter.

13. Derivatives of a monoclonal antibody or a fragment of the latter according to claim 11 or claim 12 to which a detectable marker and/or at least one therapeutic molecule is attached.

14. Hybridomas producing an antibody according to claim 11.

15. Diagnostic composition containing one or more monoclonal antibodies, fragments or derivatives of the latter as defined in any one of claims 11 to 13.

16. Therapeutic composition containing one or more monoclonal antibodies, fragments or derivatives of the latter as defined in one of claims 11 to 13.

17. Composition according to claim 16 containing derivatives containing a cytotoxic molecule or a radio-isotope.

18. Therapeutic composition containing at least one of the peptides defined in claim 7.

3. Nucleotide sequences coding for the variable regions of β

chains of human T lymphocyte receptors, corresponding to the cDNAs corresponding to all or part of the nucleotide sequences chosen from any one of the Vβ

segments corresponding to one of the sequences SEQ ID Nos. 2 to 5, and the sequences which differ from them by one or two nucleotides.

19. Therapeutic composition containing anti sense oligonucleotides corresponding to any one of the sequences of a Vβ

segment as defined in any one of claims 3 to 6.

20. Use, as primers for the amplification of DNA, of nucleotide sequences of about at least 17 nucleotides contained in any one of the sequences of a Vβ

segment as defined in any one of claims 3 to 6.

21. Use, as a detection probe, of nucleotide sequences of about at least 10 nucleotides contained in any one of the sequences of a Vβ

segment as defined in any one of claims 3 to 6.

4. Nucleotide sequences coding for the variable regions of β

chains of human T lymphocyte receptors, corresponding to the cDNAs corresponding to one of the nucleotide sequences chosen from any one of the Vβ

segments corresponding to one of the sequences SEQ ID Nos. 6 to 15, the sequences which differ from them by one or two nucleotides and fragments of the latter.

5. Nucleotide sequences according to claim 4 in which the fragments of sequences corresponding to all or part of the nucleotide sequences chosen from any one of the Vβ

segments corresponding to one of the sequences

1 to 155 of SEQ ID No. 8

1 to 125 of SEQ ID No. 9

1 to 111 of SEQ ID No. 10

and the sequences which differ from them by one or two nucleotides.

6. Nucleotide sequences coding for the variable regions of β

chains of human T lymphocyte receptors, corresponding to the cDNAs corresponding to all or part of the nucleotide sequences chosen from any one of the Vβ

segments corresponding to one of the sequences

1 to 195 of SEQ ID No. 16

1 to 99 of SEQ ID No. 17

1 to 113 of SEQ ID No. 18

1 to 186 of SEQ ID No. 19

and the sequences which differ from them by one or two nucleotides.

22. Oligonucleotides, which can be used as primers for the amplification of DNA corresponding to variable regions of β

chains of T-cell receptors, chosen form the sequences SEQ ID No. 25 to 48.

23. Use, as primers for the amplification of DNA corresponding to the variable regions of chains of T-cell receptors, of oligonucleotides according to claim 22.

24. Use according to claim 23 of oligonucleotides chosen from the sequences SEQ ID No. 45, 46, 47 and 48.

25. Detection process of nucleotide sequences coding for the Vβ

segments of T receptors or of cDNA corresponding to transcription products of the latter, in a biological sample, characterized in that it contains;

a) the amplification of DNA with at least one pair of primers formed by one of the oligonucleotides according to claim 22 and one oligonucleotide belonging to the Cβ

segment, and

b) the detection of amplified sequences with a Cβ

probe.

26. Process according to claim 25, characterized in that the amplification is carried out in the presence of a pair of control primers and detection is carried out using a control probe.

27. Diagnostic kit for the implementation of a process according to claim 25, characterized in that it contains:

a) at least one oligonucleotide according to claim 22,

b) a Cβ

primer,

c) a Cβ

probe.

28. Diagnostic kit for the implementation of a process according to claim 26, characterized in that it contains:

a) at least one oligonucleotide according to claim 22,

b) a Cβ

primer,

c) a pair of control primers,

d) a Cβ

probe

e) a control probe.

29. Kit according to claim 28 or claim 29, containing:

a) the group of 24 oligonucleotides according to claim

b) a Cβ

primer chosen form the sequences corresponding sequences SEQ ID 49 and 50,

c) a pair of control primers for the β

-actin having a sequence corresponding to sequences SEQ ID No. 52 and 53 respectively,

d) a Cβ

probe corresponding to the sequence SEQ ID No. 1

e) a control probe for the β

-actin corresponding to the sequence SEQ ID No. 54.

30. Hybridomas RO-73 and JU-74 producing anti Vβ

13 monoclonal antibodies deposited at the CNCM on the 12th February 1992 under the numbers I-1172 and I-1173.

31. Anti Vβ

13 monoclonal antibodies produced by the hybridomas according to claim 30.