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

• US 7,425,317 B2
• Filed: 03/06/2003
• Issued: 09/16/2008
• Est. Priority Date: 03/08/2002
• Status: Expired due to Fees

• 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: De Santis, Rita, Lindstedt, Ragnar, Nuzzolo, Carlo
• Primary Examiner(s): Jones; D. L
• Application Number:
  US10/506,159
• Publication Number:
  US 20050106102A1
• Time in Patent Office: 2,021 Days
• Field of Search: 424/1.11, 424/1.49, 424/1.65, 424/1.69, 424/1.73, 424/9.1, 424/78.01, 424/9.3, 424/9.4, 424/9.5, 424/9.6, 424/9.7, 424/9.8, 536/1.11, 206/223, 206/569, 206/570
• US Class Current: 424/1.49
• 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. Kit for radiotherapy or diagnosis of tumours, comprising a biotinylated anti-tenascin antibody and an avidin dimer, in which two molecules of avidin are bound via —

NH₂ groups by crosslinking with disuccinimidyl suberate.

3. The kit of claim 1, wherein the avidin is streptavidin.

2. Kit for radiotherapy or diagnosis of tumours, comprising a biotinylated anti-tenascin antibody and an avidin dimer, in which two molecules of avidin are bound via —

COOH groups by crosslinking with polyethylene glycol diamine with a molecular weight of 3400.

4. The kit of claim 2, wherein the avidin is streptavidin.