Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2007-03-07
2010-11-02
Lewis, Patrick T (Department: 1623)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C514S042000, C514S045000, C514S046000
Reexamination Certificate
active
07825096
ABSTRACT:
Disclosed are prodrugs of inactivators of O6-alkylguanine-DNA alkyltransferase (AGT). The prodrugs are cleavable by the β-glucuronidase enzyme, which is either administered to the patient or produced by necrotic tumor cells. The prodrugs are represented by the formula A-B-C, wherein A is a glucuronosyl residue linked through its 1-oxygen to the phenyl ring of B; B is a benzyloxycarbonyl group, optionally ring-substituted with one or more electron withdrawing groups; and C is an inactivator of AGT, e.g., a substituted or unsubstituted O6-benzylguanine or O6-benzyl-2′-deoxyguanosine. Also disclosed are additional inactivators of AGT, pharmaceutical compositions comprising an inactivator or prodrug and a pharmaceutically acceptable carrier, and a method of use of the inactivator or prodrug in enhancing the chemotherapeutic treatment of tumor cells in a mammal, e.g., a human, with an antineoplastic alkylating agent that causes cytotoxic lesions at the O6-position of guanine.
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Loktionova Natalia A.
Moschel Robert C.
Moschel, legal representative Matthew Karl
Pauly Gary T.
Pegg Anthony E.
Lewis Patrick T
Leydig , Voit & Mayer, Ltd.
The Penn State Research Foundation
The United States of America as represented by the Department of
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