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1. WO2000016808 - ANTIBODY DIRECTED ENZYME PRODRUG THERAPY (EDEPT) WITH GLUCORONIDASE

Publication Number WO/2000/016808
Publication Date 30.03.2000
International Application No. PCT/US1999/021308
International Filing Date 17.09.1999
Chapter 2 Demand Filed 18.03.2000
IPC
A61K 47/48 2006.01
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
47Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
48the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
CPC
A61K 47/6899
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
47Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
50the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
51the non-active ingredient being a modifying agent
68the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
6891Pre-targeting systems involving an antibody for targeting specific cells
6899Antibody-Directed Enzyme Prodrug Therapy [ADEPT]
A61P 35/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35Antineoplastic agents
B82Y 5/00
BPERFORMING OPERATIONS; TRANSPORTING
82NANOTECHNOLOGY
YSPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
5Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
Applicants
  • IMMUNOMEDICS, INC. [US]/[US] (AllExceptUS)
  • GRIFFITHS, Gary, L. [GB]/[US] (UsOnly)
  • HANSEN, Hans, J. [US]/[US] (UsOnly)
Inventors
  • GRIFFITHS, Gary, L.
  • HANSEN, Hans, J.
Agents
  • SAXE, Bernhard, D.
Priority Data
60/101,03918.09.1998US
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) ANTIBODY DIRECTED ENZYME PRODRUG THERAPY (EDEPT) WITH GLUCORONIDASE
(FR) PROCEDES ET COMPOSITIONS PERMETTANT D'AUGMENTER LA TOXICITE SPECIFIQUE CIBLE D'UN MEDICAMENT CHIMIOTHERAPIQUE
Abstract
(EN)
A method for increasing the target-specific toxicity of a drug is effected by pretargeting an enzyme to a mammalian target site, and then administering a cytotoxic drug known to act at the target site, or a prodrug form thereof which is converted to the drug $i(in situ), which drug is also detoxified to form an intermediate of lower toxicity using said mammal's ordinary metabolic processes, whereby the detoxified intermediate is reconverted to its more toxic form by the pretargeted enzyme and thus has enhanced cytotoxicity at the target site. Further enhancement can be achieved by pretargeting an enzyme which converts the prodrug to the cytotoxic drug at the target site. Kits for use with the method also are provided. The method and kits permit lower doses of cytotoxic agents, maximize target site activity and minimize systemic side effects.
(FR)
L'invention concerne un procédé permettant d'augmenter la toxicité spécifique cible d'un médicament, qui consiste à précibler une enzyme vers un site cible de mammifère, puis à administrer un médicament cytotoxique connu pour agir sur le site cible, ou une forme de promédicament de celui-ci qui est converti en médicament $i(in situ), lequel médicament est également détoxiqué pour former un intermédiaire de toxicité inférieure à l'aide des processus métaboliques ordinaires du mammifère, l'intermédiaire détoxiqué étant reconverti à sa forme plus toxique par l'enzyme préciblée et ayant renforcé ainsi la cytotoxicité au site cible. On peut encore obtenir un renforcement en préciblant une enzyme qui convertit le promédicament en médicament cytotoxique au site cible. L'invention porte également sur des trousses utilisées avec ce procédé. Le procédé et les trousses, qui permettent de réduire les doses d'agents cytotoxiques, optimisent l'activité du site cible et réduisent les effets systémiques secondaires.
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