Anti-Idiotypic Antibodies Neutralizing the Inhibitory Activity of an Inhibitory Antibody Directed Against the C1 Domain of Factor VIII

• US 20080160015A1
• Filed: 02/26/2007
• Published: 07/03/2008
• Est. Priority Date: 02/24/2006
• Status: Abandoned Application

• Current Assignee: Lfb Biomedicaments (Agence des Participations de l’Etat)
• Original Assignee: Lfb Biomedicaments (Agence des Participations de l’Etat)
• Inventors: Gilles, Jean-Guy, Saint-Remy, Jean-Marie, Behrens, Christian, Jacquemin, Marc G.
• Application Number:
  US11/817,018
• Publication Number:
  US 20080160015A1
• Time in Patent Office: Days
• US Class Current: 424/131.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: C07K 16/4241 against anti-human or anti-animal Ig

Abstract

The present invention is related to a monoclonal anti-idiotypic antibody directed against a Factor VIII inhibitor antibody binding to the C1 domain of Factor VIII, as well as to a cell line producing this monoclonal anti-idiotypic antibody, to the use of this monoclonal anti-idiotypic antibody as medicament, and more particularly to the use thereof for manufacturing a medicament intended for the treatment of haemophilia A.

Claims

1. A monoclonal anti-idiotypic antibody directed against a Factor VIII human inhibitory antibody, said inhibitory antibody being directed against the C1 domain of Factor VIII, wherein at least one CDR region (Complementarity Determining Region) of each of the light chains of said antibody contains a peptide sequence having at least 70% identity to a sequence selected from the sequences SEQ ID NO:

12, SEQ ID NO;

13, SEQ ID NO;

14 and in that at least one CDR region of each of the heavy chains of said antibody contains a peptide sequence having at least 70% identity to a sequence selected from the sequences SEQ ID NO;

9, SEQ ID NO;

10, SEQ ID NO;

11.

2. The antibody according to claim 1, wherein each CDR region of each of the light chains of said antibody contains a peptide sequence having at least 70% identity to respectively the sequences SEQ ID NO:

12, SEQ ID NO;

13 and SEQ ID NO;

14, and in that each CDR region of each of the heavy chains of said antibody contains a peptide sequence having at least 70% identity to respectively the sequences SEQ ID NO;

9, SEQ ID NO;

10 and SEQ ID NO;

11.

3. The antibody according to claim 1, wherein the variable region of each of the light chains of said antibody is coded by a nucleic acid sequence having at least 70% identity to the nucleic acid sequence SEQ ID NO:

16, and in that the variable region of each of heavy chains of said antibody is coded by an nucleic acid sequence having at least 70% identity to the nucleic acid sequence SEQ ID NO;

15.

4. The antibody according to claim 1, wherein variable region of each of the light chains of said antibody is coded by the nucleic acid sequence SEQ ID NO:

16, and in that the variable region of each of the heavy chains of said antibody is coded by the nucleic acid sequence SEQ ID NO;

15.

5. The antibody according to claim 1, wherein peptide sequence of the variable region of each of the light chains thereof is a sequence exhibiting at least 70% identity to the sequence SEQ ID NO:

18, and the peptide sequence of the variable region of each of the heavy chains thereof is a sequence exhibiting at least 70% identity to the sequence SEQ ID NO;

17.

6. The antibody according to claim 1, wherein peptide sequence deduced from the sequence SEQ ID NO:

16 is the sequence SEQ ID NO;

18 and in that the peptide sequence deduced from the sequence SEQ ID NO;

15 is the sequence SEQ ID NO;

17.

7. The antibody according to claim 1, wherein inhibitory antibody is the antibody RHD5 (deposited at the collection BCCM/LMBP under the number LMBP 6165CB).

8. The antibody according to claim 1, wherein said anti-idiotypic antibody is a mouse antibody.

9. The antibody according claim 8, wherein said anti-idiotypic antibody is a IgG1kappa

10. The antibody according to claim 1, wherein said antibody is a chimeric antibody.

11. The antibody according to claim 10, wherein said antibody is a human hybrid antibody.

12. The antibody according to claim 1, wherein said antibody is a humanized antibody.

13. The antibody according to claim 1, wherein it is selected from the group consisting in a F(ab′

)2 fragment, a Fab′

fragment, a Fab fragment, a CDR region and any modified version of any one of these fragments or region.

14. The antibody according to claim 1, wherein it is capable of being produced by the hybridoma 18B6 deposited under registration number CNCM I-3559 at the Collection Nationale de Cultures de Microorganismes (CNCM).

15. A stable cell line producing an antibody according to claim 1.

16. The stable cell line according to claim 15, selected from the group consisting of:

SP2/0, YB2/0, IR983F, the human myeloma Namalwa, PERC6, the cell lines CHO, namely CHO-K-1, CHO-Lec10, CHO-Lec1, CHO-Lec13, CHO Pro-5, CHO dhfr-, Wil-2, Jurkat, Vero, Molt-4, COS-7, 293-HEK, BHK, K6H6, NSO, SP2/0-Ag 14 and P3X63Ag8.653.

19. A DNA fragment exhibiting the sequence SEQ ID NO:

15 coding the variable region of the heavy chain of an antibody according to claim 1.

20. A DNA fragment exhibiting the sequence SEQ ID NO:

16 coding the variable region of the light chain of an antibody according to claim 1.

21. A pharmaceutical composition comprising an antibody according to claim 1 and at least one excipient and/or at least one pharmaceutically acceptable carrier.

22. The composition according to claim 21, characterized in that it comprises at least one anti-idiotypic antibody directed against an anti-FVIII antibody directed against a domain different from the C1 domain of Factor VIII.

23. The composition according to anyone of claim 21, wherein it comprises an anti-idiotypic antibody directed against an anti-FVIII antibody directed against the C2 domain of Factor VIII and/or an antibody directed against the A2 domain of Factor VIII.

24. The use of an antibody according to claim 1, for the manufacturing of a medicament.

25. The use of an antibody according to claim 1, for the manufacturing of a medicament intended for the treatment of type A haemophilia.

26. The use of an antibody according to claim 25, wherein the type A haemophilia is a haemophilia with inhibitors.

27. The use of an antibody according to claim 1, for in vitro neutralizing the inhibitory activity of an inhibitory antibody directed against the C1 domain of Factor VIII.

28. The use of an antibody according to claim 1, for in vitro detection and/or purification of Factor VIII inhibitory antibodies.

29. A medicament comprising an antibody according to claim 1.

17. The hybridoma 18B6 deposited under the registration number CNCM I-3559 at the Collection Nationale de Cultures de Microorganismes (CNCM).

18. A monoclonal anti-idiotypic antibody directed against a Factor VIII human inhibitory antibody, said inhibitory antibody being directed against the C1 domain of Factor VIII produced by the hybridoma 18B6 deposited under the registration number CNCM I-3559 at the Collection Nationale de Cultures de Microorganismes (CNCM).