Title:  Individual medicament dosing conjugate

United States Patent:  6,410,695

Assignee:  Deutsches Krebsforschungszentrum Stiftung Des Offentlichen Rechts (Heidelberg, DE)

Filed:  February 9, 1998

PCT NO:  PCT/DE96/00267

102(e) Date:  February 9, 1998

PCT PUB. Date:  August 29, 1996

The present invention relates to a conjugate comprising an active substance and a compound having a binding site for metallic compounds. In addition, this invention relates to a process for the preparation of such a conjugate and its use.

DETAILED DESCRIPTION OF THE INVENTION

In a preferred embodiment, a conjugate according to the invention has a detectable metallic compound. Such a compound may contain or consist of one or more detectable metals and/or metal ions. Examples of such metals are Zn, Cu, Co, Fe, Ni, Pt, Gd and In, which are preferably bivalent or trivalent, d^{3 +} being especially preferred. The metals and/or metal ions may be radioactive such as 111In.

In another preferred embodiment, a conjugate according to the invention has a carrier. The expression "carrier" comprises compounds of any kind which are suitable to concentrate the conjugate in a certain tissue, e.g., a tumor or a focus of inflammation.

Examples of such carriers include proteins which are not considered exogenous and polyethers. The former are preferably available in native form. In addition, they preferably have a molecular weight of up to 90,000 daltons. Especially preferred is the protein albumin, particularly human serum albumin (HSA), or transferrin. Examples of polyethers are polyethylene glycols such as methoxypolyethylene glycol, methoxypolyethylene glycol-p-nitrophenylcarbonate, methoxypolyethylene glycol succinimidylsuccinate, methoxypolyethylene glycol tresylate, methoxypolyoxyethyleneamine, methoxypolyoxyethylenecarboxylic acid and methoxypolyoxyethyleneimidazolcarbonyl. The polyethers preferably have a molecular weight of 100 to 20,000 daltons, especially preferably about 5,000 daltons.

A conjugate according to the invention may have one or more of the above carriers. If several carriers are present, they may be the same or differ from one another.

In a conjugate according to the invention, one or more active substances may be linked with one or more compounds which have binding sites for metallic compounds. In addition, the active substances and/or the compounds may be linked among one another.

Such a conjugate may also contain one or more detectable metallic compounds. They may be exempt from the linkage between the active substance or active substances and the compound or compounds or represent the same.

An above conjugate may also contain one or more carriers. They may be linked with the active substance or active substances, the compound or compounds and/or the metallic compound or metallic compounds.

A process for the preparation of a conjugate according to the present invention is also provided. Such a process carries out common reactions occurring in chemistry such as activation of an acid group and linkage of the activated acid group with an amino group. 

Conjugates according to the invention may be provided in labeled and unlabeled form. Both forms are well suited for therapeutic purposes. It is favorable to administer the labeled formed al differing times of the treatment so as to determine the absorption and distribution of the conjugate according to the invention in the body and its effect. This renders it possible to dose the conjugate individually. This represents a major advantage that has an effect especially on chemotherapy. The side effects on healthy tissue can be minimized by individually dosing the conjugate. Above all, this is achieved when the conjugate according to the invention contains a carrier that effects a concentration of the conjugate in certain tissues, e.g., tumors or foci of inflammation. Thus, the present invention enables the target-specific and dose-specific administration of pharmaceutical preparations.

Claim 1 of 9 Claims

What is claimed is:

1. A conjugate of an active substance, a compound having a binding site for metal compounds and an albumin carrier, wherein the compound is diethylenetriaminepentaacetate, and the active substance is mitoxantrone or 1,4,5,8-tetraaminoanthraquinone.

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