Glycosyl-etoposide prodrugs, a process for preparation...

Details Glycosyl-etoposide prodrugs, a process for preparation... Glycosyl-etoposide prodrugs, a process for preparation...

1999-06-30

2002-11-05

Celsa, Bennett (Department: 1627)

Drug, bio-affecting and body treating compositions

Immunoglobulin, antiserum, antibody, or antibody fragment,...

C424S085100, C424S085100, C435S188000, C530S350000, C530S387300

Reexamination Certificate

active

06475486

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to glycosyl-etoposide prodrugs, a process for the preparation thereof and the use thereof in combination with functionalized tumor-specific enzyme conjugates for treating cancers, and specifically relates to 4′-O-glycosyl-etoposides as prodrugs which can be cleaved by the action of tumor-specific enzyme conjugates to give cytotoxic active substances, the liberated active substance being suitable, by reason of its cytostatic activity, for treating cancers.
The present invention further relates to enzyme conjugates for prodrug activation, including fusion proteins of the general formula huTuMAb-L-&bgr;-Gluc, where huTuMAb is a humanized or human tumor-specific monoclonal antibody, a fragment or a derivative thereof, L is linker, and &bgr;-Gluc comprises human &bgr;-glucuronidase. These fusion proteins are prepared by genetic manipulation. huTuMAb ensures the specific localization of tumors, L connects the huTuMAb to &bgr;-Gluc in such a way that the specific properties of the two fusion partners are not impaired, and &bgr;-Gluc activates a suitable prodrug compound by elimination of glucuronic acid, where a virtually autologous system for use in humans is provided by the humanized or human fusion partners.


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