Title:  Composition and method for delivery of biologically-active factors

United States Patent:  6,274,552

Assignee:  CytImmune Sciences, Inc. (College Park, MD)

Filed:  November 10, 1997

In accordance with the present invention, a composition and method is provided that allows for the administration of a biologically-active factors to a human or animal. The present invention can be used to treat a disease with a biologically-active factor or combination of biologically-active factors, or can be used to safely vaccinate a human or animal against a biologically-active factor. It can also be used as a method for the delivery of biologically-active factors for the treatment of disease. Additionally, the present invention also includes a method of targeted drug delivery for the treatment of disease through the administration of custom complexes containing of one or more biologically active factors bound to a colloidal metal where at least one of the biologically-active factors is capable of binding a high affinity receptor on a cell surface.

SUMMARY OF THE INVENTION

The present invention satisfies the above-described needs by providing effective compositions containing normally toxic compounds that, when in combination with a colloidal metal, result in significantly reduced toxic side effects. Generally, the composition of the present invention comprises an admixture of a colloidal metal, such as gold chloride (HAuCl₄) in combination with a substance which normally is toxic to a human or animal or a substance capable of producing an immune response, wherein the composition when administered to a human or animal is less or non-toxic.

A method of use of the above composition comprises administering to a human or animal an effective amount of a composition comprising a colloidal metal, such as HAuCl₄, in combination with a substance which normally is toxic to a human or animal capable of producing an immune response, wherein the composition, when administered to a human or animal, is less toxic or non-toxic.

The use of colloidal metals in combination with normally toxic biologically-active factors may be used in the treatment of bacterial infections, viral infections, cancer and immune disease therapies, including, but not limited to, autoimmune diseases, such as rheumatoid arthritis and acquired immune deficiency. Current therapies which consist of administering factors such as interleukins to a human or animal are marginally effective but produce significant, toxic side effects. Also, the occurrence of toxic side effects limits the amount of biologically-active factors that may be administered, and therefore limits the efficacy of the therapy. Additionally, some otherwise therapeutic compounds are not used at all due to their toxicity. The combination of a colloidal metal with such biologically-active factors reduces toxicity while maintaining the therapeutic effectiveness.

The present invention also provides a method for treatment of diseases by administration of one or more biologically-active factors bound to a colloidal metal particle. The biologically-active factor is released in vivo from the colloidal metal to deliver an effective dose of the biologically-active factor over an extended period of time. The advantage of this delivery system is that lower doses of the biologically-active factor are delivered to the patient over a longer period of time. This results in reduced toxicity and fewer side-effects.

The in vivo release of the biologically-active factor from the colloidal metal is thought to be controlled by two factors: equilibrium kinetics and the amount of biologically-active factor initially bound to the colloidal metal. Equilibrium kinetics control the release of the biologically-active factor through the dilution of the factor in the body. The amount of biologically-active factor released is also directly proportional to the amount of biologically-active factor initially bound to the colloid metal particle.

Additionally, the present invention provides a method for the treatment of diseases through the targeted delivery of biologically-active factors. The method comprises administration of a composition containing a custom complex having one or more biologically-active factors bound to colloidal gold. Preferably, the composition contains at least two biologically-active factors where one of the factors is a target molecule capable of binding receptors on a cell surface. Once the composition is bound to the cell surface, the composition is internalized by the cell. After internalization, the biologically-active factors are released from the colloid metal. One advantage of this method is that smaller amounts of biologically-active factor can be used than that with previously known methods because the factor is transported across the cell membrane without disruption of the cell membrane. This method also provides cellular specificity, and, once bound to the cell, the gold-bound, biologically-active factor may serve as an immobilized source of releasable biologically-active factor--a constant release depot.

Accordingly, it is an object of the present invention to provide a composition that is capable of reducing the toxicity of biologically-active factors.

A further object of the present invention is to provide a composition containing higher concentrations of biologically-active factors than are currently utilized due to the toxicity of the substances.

Another object of the present invention is to provide a composition to be used in cancer therapies which results in reduced side effects from toxicity.

Yet another object of the present invention is to provide a composition for immune disease therapy which results in reduced side effects from toxicity.

Another object of the present invention is to provide a therapeutic method for immune disease therapy which results in reduced toxic side effects and maintains its beneficial effects.

Yet another object of the present invention is to provide a method of vaccinating a human or animal against a normally toxic biologically-active factor.

A further object of the present invention is to provide a method for the slow release of biologically-active factors.

Another object of the present invention is to provide a therapeutic method for the treatment of cancer through the extended in vivo release of biologically-active factors.

Another object of the present invention is to provide a therapeutic method for the treatment of immune deficient diseases through the extended in vivo release of biologically-active factors.

Another object of the present invention is to provide custom complexes composed of one or more biologically-active factors bound to a colloidal metal for the treatment of diseases.

It is another object of the present invention is to provide custom complexes composed of one or more biologically-active factors bound to a colloidal metal for the treatment of cancer, both solid tumors as well as blood-borne cancers.

Yet another object of the present invention is to provide custom complexes composed of one or more biologically-active factors bound to a colloidal metal for the treatment of autoimmune diseases.

Still another object of the present invention is to provide custom complexes composed of one or more biologically-active factors bound to a colloidal metal for the treatment of hormone deficiency diseases.

It is another object of the present invention is to provide custom complexes composed of one or more biologically-active factors bound to a colloidal metal for the treatment of hormone abnormalities due to hypersecretion.

It is yet another object of the present invention is to provide custom complexes composed of one or more biologically-active factors bound to a colloidal metal for the treatment of infectious diseases, such as septic shock.

A further object of the present invention is to provide custom complexes composed of one or more biologically-active factors bound to a colloidal metal for the treatment of genetic diseases.

It is another object of the present invention is to provide custom complexes composed of one or more biologically-active factors bound to a colloidal metal for the treatment of immune deficiency diseases.

A further object of the present invention is to provide custom complexes composed of one or more biologically-active factors where at least one of the biologically-active factors is a target molecule capable of binding a high affinity receptor on the cell surface.

Yet another object of the present invention is to provide a method of delivering a biologically-active factor to the interior of a cell.

Another object of the present invention is to provide a method of delivering a biologically-active factor to the interior of a cell by administering a composition containing a custom complex composed of one or more biologically-active factors bound to a colloidal metal where at least one of the biologically-active factors is a target molecule capable of binding a high affinity receptor on a cell surface.

Yet another object of the present invention is a therapeutic method for the treatment of cancer by administering a composition containing a custom complex comprised of one or more biologically-active factors bound to a colloidal metal where at least one of the biologically-active factors is a target molecule capable of binding a high affinity receptor on a cell surface.

Yet another object of the present invention is a therapeutic method for the treatment of immune deficiency diseases by administering a composition containing a custom complex comprised of one or more biologically-active factors bound to a colloidal metal where at least one of the biologically-active factors is a target molecule capable of binding a high affinity receptor on the cell surface.

Claim 1 of 21 Claims

What is claimed is:

1. A composition capable of targeting a particular tissue comprising a biologically-active factor selected from the group consisting of TNF-.alpha. and lymphotoxin and a target molecule admixed with or bound to a colloidal metal.

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