Drug – bio-affecting and body treating compositions – Extract – body fluid – or cellular material of undetermined... – Derived from musculoskeletal system – other than cardiac muscle
Reexamination Certificate
2001-08-28
2003-03-25
Witz, Jean C. (Department: 1651)
Drug, bio-affecting and body treating compositions
Extract, body fluid, or cellular material of undetermined...
Derived from musculoskeletal system, other than cardiac muscle
Reexamination Certificate
active
06537587
ABSTRACT:
FIELD OF THE INVENTION
The present invention generally concerns a novel method for the production of a composition which inhibit growth of tumor cells and stimulates proliferation of normal cells. The invention further concerns the use of such a composition in the prevention and treatment of various malignant disorders and diseases, as well as in combination with chemotherapeutical treatments.
GLOSSARY
The following are terms which will be used throughout the description and claims and which should be understood in accordance with the invention to mean as follows:
Biologically active—having the following biological activities: inhibition of proliferation of tumor cells, stimulation of proliferation of leukocytes, mainly neutrophils, anti-metastatic effect in vivo and reduction of cytotoxic side effects of chemotherapeutic treatments.
Composition of matter—a composition comprising one or more substances each having one or more biological activities.
Muscle tissue—muscle tissue or cells obtained directly from an animal. For preparation of the biologically active composition from the muscle tissue or cells, the muscle tissue or cells may be used immediately after obtaining them from the animal or they may be maintained for various periods of time under conditions which enable, eventually, to prepare the composition of the invention therefrom.
Target cells—the cells affected by the composition.
Anti-metastatic effect—effect of preventing or reducing the metastatic process in a subject. The effect may be manifested in the prevention of appearance of metastatic foci, in a decrease in the rate of occurrence of metastatic tumors, or a decrease in the number of metastatic tumors appearing in the individual or in a decrease in the rate of cancer related mortality.
Chemoprotective effect—reduction of the cytotoxic side effect of chemotherapy and specifically of the reduction in the number of white blood cells and neutrophils in an individual treated with a chemotherapeutic treatment.
BACKGROUND OF THE INVENTION
Small molecules having a molecular weight of less than 3 kD and which inhibit the proliferation of various tumor cells were previously described in International Application Publication No. WO 96/09060. These molecules, termed “muscle factor” (NE), were shown, on the one hand, to have inhibitive activity on tumor cells and, on the other hand, to promote proliferation of non-tumor, normal cells such as fibroblasts and bone marrow cells in vitro. In addition the MFs where shown to exert a chemoprotective effect in vivo in that they decrease or prevent the reduction in the number of leukocytes and percentage of neutrophils in an individual receiving chemotherapeutic treatment. The MFs described above were produced from cultured medium of muscle cells or leukocytes grown in culture.
GENERAL DESCRIPTION OF THE INVENTION
In accordance with the present invention it was found that a very potent biologically active composition of matter may relatively easily be prepared in large quantities from muscle tissue obtained from various animal sources.
The present invention thus provides a method for preparing a biologically active composition of matter comprising:
(i) providing muscle tissue;
(ii) treating the tissue in a liquid medium under conditions in which said composition of matter contained within the tissue is freed into the medium as a supernatant;
(iii) separating the supernatant from cell matter; and
(iv) separating from the supernatant a fraction comprising substances having a molecular weight of below about 10,000 Dalton, preferably below about 3,000 Dalton
said fraction being said biologically active composition of matter.
The muscle tissue from which the biologically active composition of matter of the invention is prepared may, for example, be chicken meat, may be turkey meat, beef, pork meat, etc. The biologically active composition of matter of the invention exerts its effect across species. Thus, for example, said composition of matter which is prepared from chicken muscle, will affect mammalian, including human target cells.
The composition of matter of the invention may be prepared from the muscle tissue immediately following the extraction of the muscle tissue from the animal. Alternatively, the extracted muscle tissue may be maintained for various periods of time following the extraction of the muscle tissue from the animal, under such conditions which will not bar the eventual preparation of the biologically active composition of matter therefrom. Such conditions may, for example, be storage in the cold, at times with a preservative. Furthermore, the meat may additionally be cooked, typically mildly, and stored for a period of time within the broth in which it was cooked. Such cooking, by itself, gives rise to release of the composition of matter to the surrounding medium and thus the broth, may also at times be used for the preparation of the inventive composition of matter.
The biologically active composition of matter obtained from muscle tissue may be in the form of a natural crude extract. The natural crude extract may be maintained in its original liquid form or may be dried, e.g. by lyophilization. In addition, the composition of matter of the invention may also be in the form of a purified extract. In order to obtain a more purified composition of matter, the fraction separated from the supernatant, as described above, may be subjected to additional purification steps such as, for example, fractionation by chromatography, typically high pressure liquid chromatography (HPLC), e.g. reverse phase HPLC. In addition, the original preparation may be subjected to additional filtration stages, may further be purified by dialysis, etc.
The biologically active composition of matter of the invention obtained by the above method was found to have several biological activities. First, the composition inhibits proliferation of malignant cells. Against this, the composition of matter of the invention does not inhibit proliferation of non-malignant cells and moreover, at times, stimulates proliferation of white blood cells, specifically neutrophils.
An additional biological activity of the composition of matter of the invention is its anti-metastatic effect in vivo. Administration of the composition of matter in a variety of animal models showed that it reduces the number of metastatic foci in the tested animals as compared to tumor-bearing animals which were not treated with the composition of matter of the invention.
In addition to the above activities, the composition of matter of the invention also has a chemo-protective effect in an individual receiving chemotherapeutic treatment. Such therapeutic treatments have severe cytotoxic side effects on a variety of cells including hematopoietic cells such as bone marrow cells, leukocytes, particularly neutrophils, and others. The composition of matter of the invention reduces or inhibits some of the toxic effects of such therapeutic treatments resulting in a more limited reduction in the number of the non-malignant leukocytes and, at times even an increase in the number of white blood cells, mainly neutrophils, in individuals receiving the composition of the invention in combination with the therapeutic treatment.
The composition of matter of the invention exerts its biological activity both when administered parenterally, as well as when administered orally. Oral administration of the composition of matter of the invention is a preferred mode of administration in accordance with the invention, as also noted below.
The present invention also provides a biologically active composition of matter having the following characteristics:
(i) it is derived from muscle tissue;
(ii) it filters through a filter with a maximal molecule weight cut-off of about 10,000 Daltons, preferably less than 3,000 Daltons;
(iii) it has a biological effect of inhibiting proliferation of tumor cells and stimulation of proliferation of leukocytes and neutrophils.
Preferably, said composition of matter also exhibits an anti-metastatic effect. Desirably, the i
Can-Fite Biopharma Ltd.
Witz Jean C.
LandOfFree
Compositions containing muscle-derived active agents does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compositions containing muscle-derived active agents, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compositions containing muscle-derived active agents will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3079329