Yeda Research and Develpment & Co. Ltd

Ofer Lider

Irun R Cohen

Raanan Margalit

Rami Hershkoviz

Liora Cahalon

Oded Shoseyov

Matityahu Fridkin

Francisco Javier Quintana

Alexandra Zanin-Zhorov

Eran Yavin

Guy Tal

Amiram Ariel

Meirav Pevsner

Ronen Alon

Noam Greenspoon

The present invention provides novel uses for peptide p277&#x2014;positions 437-460 of human heat shock protein 60 (HSP60)&#x2014;in modulation of immune responses and inflammatory diseases. The invention further provides novel uses for HSP60 and p277 in the treatment or prevention of hepatic disorders. The invention discloses methods for treating, preventing or ameliorating the symptoms of T cell mediated inflammatory and autoimmune disorders, including hepatic disorders, which comprise administering to a subject in need thereof a composition comprising as an active ingredient an effective quantity of a molecule selected from: HSP60, p277, fragments, analogs, homologs and derivatives thereof, and nucleic acids encoding same. Also disclosed are T cell vaccination methods for treating or preventing T cell mediated disorders.

HSP60, HSP60 peptides and T cell vaccines for immunomodulation

Substances comprising carboxylated and/or sulfated oligosaccharides in substantially purified form, including compositions containing same and methods of using same, are disclosed for the regulation of cytokine activity in a host. For instance, the secretion of Tumor Necrosis Factor Alpha (TNF-&#x3b1;) can be either inhibited or augmented selectively by administration to the host of effective amounts of substances or their compositions comprising specific oligosaccharides in substantially purified form. Thus, the present invention also relates to pharmaceutical compositions and their use for the prevention and/or treatment of pathological processes involving the induction of active cytokine secretion, such as TNF-&#x3b1;. The invention also relates to the initiation of a desirable immune system-related response by the host to the presence of activators, including pathogens. The substances and pharmaceutical compositions of the present invention may be daily, at very low effective doses, typically below 0.1 mg/kg human, or at intervals of up to about 5-8 days, preferably once a week.

Compositions for the regulation of cytokine activity

A treatment for cancer, and in particular, of therapeutic compounds which block the ability of cytokines and chemokines to promote metastasis of malignant cells. The therapeutic compound comprises a carboxylated and/or sulfated oligosaccharide, preferably in a substantially purified form, which is a heparin or heparan-sulfate derived saccharide compound. In one embodiment of the present invention, the carbohydrate or oligosaccharide has a molecular weight of no more than about 3000 daltons, preferably lying in the range of about 400 to about 2000 daltons, most preferably between about 400 and about 1100 daltons. Generally, substances of the present invention inhibit tumor cell migration, as determined by biological assays, and comprise molecules of various sugar units of which the basic unit of activity is associated with a disaccharide. However, larger oligosaccharide chains of up to about 10 sugar units, containing the basic disaccharide unit of activity can also function to inhibit such activity.

Anti-cancer therapeutic compounds

Synthetic anti-inflammatory peptides derived from the sequence of IL-2 are provided. Parent peptides of the sequences Ile-Val-Leu, Glu-Phe-Leu-Asn-Arg-Trp-Ile-Thr (SEQ ID NO:1) and Arg-Met-Leu-Thr (SEQ ID NO:2), were obtained by elastase enzymatic digestion of IL-2, synthesized and modified. The peptides are useful in conditions of acute and chronic inflammation such as in autoimmune diseases.

Anti-inflammatory peptides derived from IL-2 and analogues thereof

A pharmaceutical composition for the regulation of cytokine activity in a subject. The composition features an effective amount of an oligosaccharide to inhibit the cytokine activity, preferably through inhibition of TNF-alpha activity. The oligosaccharide is more preferably up to four saccharide units in length, and optionally and more preferably, is N-sulfated with at least one other sulfur moeity. The compositions are useful for the treatment of various pathological conditions related to, caused by or promoted through, cytokine activity.

Substances comprising disaccharides and substances comprising carboxylated and/or sulfated oligosaccharides in substantially purified form, and methods of using same, are disclosed for the regulation of cytokine activity in a host. For instance, the secretion of active Tumor Necrosis Factor Alpha (TNF-.alpha.) can be either inhibited or augmented selectively by administration to the host of an effective amount of a substance of the invention. Thus, the present invention also relates to pharmaceutical compositions and their use for the prevention and/or treatment of pathological processes involving the induction of active cytokine secretion, such as TNF-.alpha.. The invention also relates to the initiation of a desirable immune system-related response by the host to the presence of activators, including pathogens. The substances and pharmaceutical compositions of the present invention may be administered daily, at very low effective doses, typically below 0.1 mg/kg human, or at intervals of up to about 5-8 days, preferably once a week.

Compositions and methods for regulation of active TNF-.alpha.

The present invention relates to pharmaceutical compositions for the prevention and/or treatment of pathological processes involving the induction of TNF-.alpha. secretion comprising a pharmaceutically acceptable carrier and a low molecular weight heparin (LMWH). In the pharmaceutical compositions of the present invention, the LMWH is present in a low effective dose and is administered at intervals of about 5-8 days. Furthermore, the LMWH is capable of inhibiting in vitro TNF-.alpha. secretion by resting T cells and/or macrophages in response to T cell-specific antigens, mitogens, macrophage activators, disrupted extracellular matrix (dECM), laminin, fibronectin, and the like.

Methods of using low molecular weight heparins for prevention or

Methods for regulation of active TNF-.alpha.

The present invention relates to methods for the prevention and/or treatment of pathological processes involving the induction of TNF-.alpha. secretion comprising a pharmaceutically acceptable carrier and a low molecular Weight heparin (LMWH). In the pharmaceutical compositions of the present invention, the LMWH present in a low effective dose and is administered at intervals of about 5-8 days. Furthermore, the LMWH is capable of inhibiting in vitro TNF-.alpha. secretion by resting T cells and/or macrophages in response to T cell-specific antigens, mitogens, macrophage activators, disrupted extracellular matrix (dECM), laminin, fibronectin, and the like.

Methods of using low molecular weight heparins for treatment of

A method of inhibition of cellular and molecular level biological interactions which are dependent on RGD interactions is disclosed. The method comprises administering a compound of the formula I

Method of inhibition of cellular and molecular level biological

The present invention relates to methods for the prevention and/or treatment of pathological processes involving the induction of TNF-.alpha. secretion comprising a pharmaceutically acceptable carrier and a low molecular weight heparin (LMWH). In the pharmaceutical compositions of the present invention, the LMWH is present in a low effective dose and is administered at intervals of about 5-8 days. Furthermore, the LMWH is capable of inhibiting in vitro TNF-.alpha. secretion by resting T cells and/or macrophages in response to T cell-specific antigens, mitogens, macrophage activators, disrupted extracellular matrix (dECM), laminin, fibronectin, and the like.

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Kfar Bilu, Israel

Ofer Lider