Apoptosis-mimicking synthetic entities and use thereof in medical treatment

Abstract

Synthetic and semisynthetic bodies having a three-dimensional structure, sized and shaped to resemble apoptotic cells and apoptotic bodies, and having phosphatidyl serine (PS) molecules on the surface thereof, are administered to a patient, to alleviate a variety of disorders such as T-cell mediated disorders (autoimmune conditions). The bodies are believed to trigger an apoptosis-like mechanism in the patient.

1 . A method for treating a T-cell function-mediated disorder comprising administering to a mammalian patient a non-toxic effective T-cell function-mediated disorder-treating amount of PS-carrying bodies wherein the progression of the T-cell function-mediated disorder is inhibited and/or the symptoms of the disorder are reduced. 
     
     
         2 . A method for treating an inflammatory disorder comprising administering to a mammalian patient a non-toxic effective inflammatory disorder-treating amount of PS-carrying bodies, wherein the progression of the inflammatory disorder are inhibited and/or the symptoms of the disorder are reduced. 
     
     
         3 . A method for treating an endothelial function disorder comprising administering to a mammalian patient a non-toxic effective endothelial function disorder-treating amount of PS-carrying bodies, wherein the progression of the endothelial function disorder is inhibited and/or the symptoms of the disorder are reduced. 
     
     
         4 . A method for treating an immune system disorder characterized by an inappropriate cytokine expression comprising administering to a mammalian patient a non-toxic effective inappropriate cytokine expression-treating amount of PS-carrying bodies, wherein the progression of the disorder are inhibited and/or the symptoms of the reduced. 
     
     
         5 . The method of  claims 1  wherein the amount of PS-carrying bodies administered is from about 500 to about 500,000,000 bodies. 
     
     
         6 . The method of  claim 5  wherein the amount of PS-carrying bodies administered is from about 10,000 to about 10,000,000 bodies. 
     
     
         7 . The method of  claim 6  wherein the amount of PS-carrying bodies administered is from about 200,000 to about 2,000,000 bodies. 
     
     
         8 . The method of  claims 1  wherein the PS-carrying bodies comprise from about greater than 65% PS. 
     
     
         9 . The method of  claims 1  wherein the PS-carrying bodies comprise from about 65% to about 90% PS. 
     
     
         10 . The method of  claims 1  wherein the PS-carrying bodies comprise from about 70% to about 80% PS. 
     
     
         11 . The method of  claims 1  wherein the PS-carrying bodies comprise about 75% PS. 
     
     
         12 . The method of  claims 1  wherein said PS-carrying bodies are liposomes. 
     
     
         13 . The method of  claim 12  wherein said liposomes have a diameter of about 50 nanometers-500 microns. 
     
     
         14 . The method of  claim 12  wherein said liposomes have a diameter of about 50 nanometers-1000 nanometers. 
     
     
         15 . The method of  claims 1  wherein said PS-carrying bodies are biocompatible non-liposomal synthetic bodies. 
     
     
         16 . The method of  claim 15  wherein said biocompatible non-liposomal synthetic bodies have a diameter of about 50 nanometers-500 microns. 
     
     
         17 . The method of  claim 15  wherein said biocompatible non-liposomal synthetic bodies have a diameter of about 50 nanometers-1000 nanometers. 
     
     
         18 . A pharmaceutical composition comprising pharmaceutically acceptable biocompatible synthetic or semi-synthetic bodies for administration to a mammalian patient and a pharmaceutically acceptable carrier, wherein at least a portion of said bodies have a conformation and size corresponding to mammalian apoptotic bodies wherein the surface of said bodies have been modified to contain a plurality of ligands for one or more phosphatidylserine receptors; which bodies are capable of binding to a phosphatidylserine receptor on an antigen presenting cell when administered to the mammalian patient. 
     
     
         19 . The pharmaceutical composition of  claim 18 , wherein the pharmaceutically acceptable synthetic or semi-synthetic body is a liposome. 
     
     
         20 . The pharmaceutical composition of  claim 1  comprising a unit dosage form. 
     
     
         21 . A pharmaceutical composition comprising a pharmaceutical carrier and biocompatible non-liposomal synthetic bodies for administration to a mammalian patient wherein the non-liposomal biocompatible synthetic bodies comprise pharmaceutically acceptable bodies have a conformation and size corresponding to mammalian apoptotic bodies wherein the surface of said pharmaceutically acceptable body has been modified to contain a plurality of ligands for one or more phosphatidylserine receptors; which biocompatible synthetic bodies are capable of binding to a phosphatidylserine receptor on an antigen presenting cell when administered to the mammalian patient. 
     
     
         22 . The pharmaceutical composition of  claim 21  wherein the biocompatible non-liposomal synthetic body is selected from hydroxyethylcellulose, polyethylene glycol, hydroxethyl starch, polyvinylprrolidone, polysaccharides, polystyrene and agarose. 
     
     
         23 . The pharmaceutical composition of  claim 21  comprising a unit dosage form. 
     
     
         24 . A process for alleviating the symptoms of a disorder in a mammalian patient, which comprises administering to the patient an effective amount of PS-carrying bodies as defined herein. 
     
     
         25 . The process of  claim 24  wherein the disorder is a T-cell mediated disorder, an inflammatory disorder, an endothelial dysfunction disorder or an inappropriate cytokine expression disorder. 
     
     
         26 . The process of  claim 24  wherein the administration is conducted intra-arterially, intravenously, intramuscularly or subcutaneously, as a liquid suspension of PS-carrying bodies in a biocompatible liquid. 
     
     
         27 - 28 . (canceled) 
     
     
         29 . Three-dimensional synthetic and semi-synthetic bodies having shapes and dimensions ranging from those resembling mammalian cells to those resembling those of apoptotic bodies produced by apoptosis of mammalian cells, and having phosphatidyl serine molecules on the surface thereof. 
     
     
         30 . Bodies as claimed in  claim 29 , in the form of liposomes having phosphatidyl serine molecules bonded to the membrane outer surfaces. 
     
     
         31 . Lyophilized or freeze dried PS-carrying bodies. 
     
     
         32 . A kit of parts comprising the lyophilized or freeze dried PS-carrying bodies of  claim 26  and a pharmaceutically acceptable carrier. 
     
     
         33 . The kit of  claim 31  wherein the pharmaceutically acceptable carrier is selected from physiological sterile saline, sterile water, pyrogen-free water, isotonic saline, and phosphate buffer solution. 
     
     
         34 - 46 . (canceled)