Avidin dimers effective in increasing the concentration of radioactive biotin in pretargeted radioimmunotherapy

• US 20050106102A1
• Filed: 03/06/2003
• Published: 05/19/2005
• Est. Priority Date: 03/08/2002
• Status: Active Grant

• Current Assignee: Sigma-Tau Industrie Farmaceutiche Riunite SPA (Alfasigma S.p.A.)
• Original Assignee: Sigma-Tau Industrie Farmaceutiche Riunite SPA (Alfasigma S.p.A.)
• Inventors: Rita, De Santis, Carlo Antonio, Nuzzolo, Ragnar, Lindstedt
• Granted Patent: US 7,425,317 B2
• Time in Patent Office: Days
• US Class Current: 424/9.100
• CPC Class Codes: A61K 47/665 the pre-targeting system, clearing therapy or rescue therapy involving biotin-(strept) avidin systems
• CPC Class Codes: A61K 47/6898 using avidin- or biotin-conjugated antibodies
• CPC Class Codes: A61K 51/0497 conjugates with a carrier being an organic compounds
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07K 16/30 from tumour cells

Abstract

Dimers of avidin and streptavidins (diavidins) are described wherein the linker is suberate, which in turn, is bound to different functional groups (—NH2 o-COOH) of avidin. As compared to avidin, the diavidins have shown the ability to increase the amount of labelled biotin on the target, when used in an in vitropretargeting test using supported human tenascin, the biotinylated anti-tenascin monoclonal antibody (Mab-B), avidin/diavidin, and biotin-3H. The use of such diavidins is also described in cancer diagnosis and anticancer therapy based on the three-step pretargeted radioimmunotherapy procedure.

Claims

1. Avidin dimer, in which two molecules of avidin are bound via the NH2 groups by means of suberate.

3. Dimer according to claim 1, wherein the avidin is streptavidin.

4. Pharmaceutical and/or diagnostic composition containing the dimer of claim 1.

5. Composition according to claim 4, which can be administered parenterally or locoregionally.

6. Use of the dimer of claim 1 for the preparation of medicaments and diagnostic means.

7. Use of the dimer of claim 1 for the preparation of a medicament useful in the diagnosis or treatment of pathological conditions of organs or tissues.

8. Use of the dimer of claim 1 for the preparation of medicaments or diagnostic means useful for the therapy or diagnosis of tumours.

9. Use of the dimer of claim 1 in pretargeting methods using antibodies in vitro.

10. Use of the dimer of claim 1 for the preparation of a medicament useful for the treatment of disease using pretargeting methods with antibodies.

11. Use according to claim 10, where said disease is a tumour.

12. Use according to claim 10, where said antibody is an anti-tenascin antibody.

13. Use according to claim 12, where said anti-tenascin antibody is monoclonal.

14. Use according to claim 10, where said medicament is part of a kit which is useful in the diagnosis and treatment of tumours by means of the three-step pretargeting technique.

15. Use according to claim 14, where said kit contains a radiopharmaceutical.

16. Kit for the radiotherapy or diagnosis of tumours, characterised in that at least one of the components of said kit contains a dimer according to claim 1.

17. Kit according to claim 16, for use in the pretargeting technique.

18. Kit according to claim 17, where said pretargeting technique is three-step.

19. Kit according to claim 16, containing a biotinylated anti-tenascin.

20. Kit according to claim 19, where said antibody is a monoclonal antibody.

2. Avidin dimer, in which two molecules of avidin are bound via the COOH groups by means of polyethylene glycol with a molecular weight of 3400.