Drug – bio-affecting and body treating compositions – Conjugate or complex of monoclonal or polyclonal antibody,... – Conjugated via claimed linking group – bond – chelating agent,...
Patent
1996-07-22
1998-07-28
Knode, Marian C.
Drug, bio-affecting and body treating compositions
Conjugate or complex of monoclonal or polyclonal antibody,...
Conjugated via claimed linking group, bond, chelating agent,...
4241781, 4242831, 424502, 514943, 436547, A61K 39395, A61K 4744
Patent
active
057859698
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP94/02827, filed Aug. 25, 1994.
The present invention relates to pharmaceutical and diagnostic compositions containing antibody aggregates and a drug or a marker and a method for drug targeting and diagnostics. More specifically said invention relates to a composition containing aggregates of antibodies, wherein a drug or any other marker probe is solubilized in said aggregates. The invention relates also to a process for the preparation of said pharmaceutical and diagnostic composition and to the method of targeting the aggregates to specific molecules or sites in the body, or in vitro tests.
Since the aggregates are composed of antibodies, they are capable of recognizing specific molecules, and therefore can be used for drug targeting or diagnostic purposes, provided that suitable molecules--drugs, fluorescent markers, etc.--can be loaded into these aggregates.
BACKGROUND OF THE INVENTION
The present invention relates to drug targeting, or marker molecule targeting, by small antibody aggregates, while the targeting molecules also form the carrier for specific targeted molecule. The advantages of being able to direct a drug to the tissue or cells where it is required, and to minimize the amount delivered to inappropriate sites has implications for many clinical situations, such as cancer chemotherapy, inflammations and viral infections (Davis S. S et al. Drug Exptl. Clin. Res. 9 632 1985).
In the past, several attempts to achieve drug targeting were reported, by using polyclonal and monoclonal antibodies. These attempts include: polymer molecule such as dextran. particles, by covalent linkage by direct adsorption or by adsorption via protein A. modification of the antibody. binding process for each drug to be tested. reaction between the drug and the antibody. attachment. solid particle. to overcome problems related to size of particles, and therefore destruction or clearance of the particles from the body. overcomes most of the above disadvantages, by the use of antibody aggregates. The antibody-aggregates can also be used for diagnostic purposes, namely detection of specific antigens, in vivo and in vitro tests. This can be achieved by solubilizing various probes in the aggregates, such as hydrophobic fluorescent molecules, or radioactive molecules.
BRIEF DESCRIPTION OF THE INVENTION
The present invention relates to pharmaceutical and diagnostic compositions containing an antibody-aggregates and a drug or a marker wherein the antibody-aggregates are capable of solubilizing hydrophobic molecules, and the drug or the marker probe are solubilized in the aggregates.
The present invention further relates to a process for the preparation of pharmaceutical and diagnostic compositions comprising: of a surface-active agent. Various chain lengths and degree of modifications are possible. aggregates are formed.
The present invention also relates to a method for drug targeting towards specific sites in the body (such as antigenic determinants), comprising administration of an effective amount of pharmaceutical to a host. The present invention also relates to a method for in vivo and in vitro diagnostics, in which the aggregates contain molecules which can be detected by suitable instruments.
DESCRIPTION OF THE INVENTION
The new method for drug targeting is based on formation of aggregates of antibodies. These aggregates are formed by covalent attachment of hydrophobic chains to various antibodies, hence leading to micelle-like structures in a similar way to that in which classical surfactant ("detergents") may form micelles. These antibody aggregates have unique properties, especially two: (1) the aggregates are capable of solubilizing hydrophobic molecules, (2) the antibodies may recognize specific antigens. Therefore, such aggregates can be used for drug targeting, while the targeting molecules (the antibodies) also play the role of a conventional carrier. The aggregates are very small--about 200-1000 .ANG. in diameter, hence they might overcome problems which are encoun
REFERENCES:
patent: 4957735 (1990-09-01), Huang
patent: 5135736 (1992-08-01), Anderson et al.
Chekhonin et al., Fatty acid acylated Fab-fragments of antibodies to neurospecific proteins as carriers for neuroleptid targeted delivery in brain. FEBS Letters 287 (1,2):149-152, 1991.
Huang et al., Monoclonal Antibody Covalently Coupled with Fatty Acid. Journal of Biological Chemistry 255:8015-8018, 1980.
Magdassi Shlomo
Rones Zichria Zazkay
Toledano Ofer
Knode Marian C.
Wortman Donna C.
Yissum Research Development Company of The Hebrew University of
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