Vasogen Ireland Limited

Vasogen, Inc.

Hyal Pharmaceutical Corporation

Intermune Life Sciences, Inc.

Anthony E Bolton

Arkady Mandel

Alan Drizen

Duncan John Stewart

Daniel Sauder

Daniel N Sauder

Synthetic and semisythetic 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 and apoptosis-like mechanism in the patient.

Apoptosis-mimicking synthetic entities and use thereof in medical treatment

Treatment and/or prophylaxis of endothelial dysfunction-related disorders in mammalian patients is effected by administering to the patient effective amounts of apoptotic bodies and/or apoptotic cells.

Apoptotic entities for use in treatment of endothelium dysfunction disorders

Endothelin-related disorders in mammals can be alleviated by administration to such patients of one or more aliquots of mammalian blood subjected to two or more stressors selected from temperature stressors, electromagnetic emissions and oxidative environments.

Treatment of endothelin-related disorders

An improved method for treating or preventing a pathological condition in a mammalian subject in which modified mammalian blood is administered to the subject. The method comprises administering to the subject from two to four aliquots of modified mammalian blood, with the administration of any pair of consecutive treatments either being on consecutive days or being separated by a rest period of 1 to 21 days. The treatment is useful for treating or preventing a wide range of pathological conditions in which modified mammalian blood is effective, including preconditioning a mammalian subject to better withstand the adverse effects of ischemic stress, atherosclerosis and rheumatoid arthritis.

Method for treating mammals with modified mammalian blood

Treatment and/or prophylaxis, in mammalian patients, of neurodegenerative and other neurological medical disorders is effected by administering to the patient effective amounts of apoptotic bodies and/or apoptotic cells, preferably those derived from the patient's own white blood cells, e.g. by extracorporeal treatment of the patient's blood cells to induce apoptosis and administration of the apoptotic bodies and/or cells so formed to the patient.

Apoptotic entities for use in treatment of neurodegenerative and other neurological disorders

Disclosed are methods for treating and preventing neurological disorders which have a significant inflammatory component. The methods of the present invention involve extracting blood from a patient, subjecting the blood ex vivo to at least one stressor selected from the group consisting of an oxidative environment, thermal stress and UV light, and then re-administering the blood to the patient, thereby reducing inflammation.

Compositions containing apoptotic entities

An improved method for treating or preventing a pathological condition in a mammalian subject in which modified mammalian blood is administered to the subject. The method comprises administering to the subject from two to four aliquots of modified mammalian blood, with the administration of any pair of consecutive treatments either being on consecutive days or being separated by a rest period of l to 21 days. The treatment is useful for treating or preventing a wide range of pathological conditions in which modified mammalian blood is effective, including preconditioning a mammalian subject to better withstand the adverse effects of ischemic stress, atherosclerosis and rheumatoid arthritis.

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.

Vasospastic disorders are treated by administering to the patient an aliquot of autologous blood which has been subjected simultaneously to heat, ultraviolet irradiation and oxidative environment so as to render the blood aliquot capable of generating in the patient's blood stream after administration a population of stimulated leukocytes having upregulated expression of CD25 cell surface markers, along with an enhancement of endothelial function in the patient.

Endothelial lining effects and treatment of vasospastic disorders

A method of treating or preventing atherosclerosis in a mammalian subject comprises: (a) extracting the aliquot of blood from the subject; (b) treating the aliquot of blood ex vivo with at least one stressor selected from the group consisting of an oxidizing agent, ultraviolet radiation and elevated temperature; and (c) administering the aliquot of blood treated in step (b) to the subject. Preferably, the aliquot has a volume of from about 0.01 ml to about 400 ml and is treated simultaneously by ozone gas and ultraviolet radiation at a temperature of from 37-55&deg; C.

Method of treating atherosclerosis

An autoimmune vaccine is provided for administration to human patients to alleviate the symptoms of autoimmune diseases such as rheumatoid arthritis. The vaccine comprises an aliquot of the patient's blood, containing, inter alia, leukocytes having upregulated expression of various cell surface markers and lymphocytes containing decreased amounts of certain stress proteins. It is produced by subjecting the blood aliquot extracorporeally to certain stressors, namely oxidizing agents, UV radiation and elevated temperature.

Treatment of autoimmune diseases

Reflex sympathetic dystrophy in a human patient is treated by collecting an aliquot of the patient's blood (e.g. 10 cc in volume), and subjecting it simultaneously to ozone/oxygen mixture and ultraviolet light, at a predetermined, elevated (e.g. 42.5.degree. C.) temperature, for approximately 3 minutes. After cooling, the treated blood aliquot is reinjected into the patient via the gluteal muscle. Reflex sympathetic dystrophy is alleviated following a course of such treatments.

Treatment of chronic post-traumatic pain syndromes

A method of increasing the nitric oxide concentration in the blood of a human, which comprises: (a) contacting from about 0.01 ml to about 400 ml of blood with a nitric oxide concentration-increasing effective amount of ozone gas and ultraviolet radiation; and (b) administering the treated blood to a human. The method of the invention is useful for treating a variety of conditions benefitted by increased blood levels of nitric oxide.

Method of increasing the concentration of nitric oxide in human blood

A method of inhibiting the aggregation of blood platelets in a human, which comprises: (a) contacting from about 0.01 ml to about 400 ml of blood with a blood platelet aggregation-inhibiting effective amount of ozone gas and ultraviolet radiation; and (b) administering the blood treated in step (a) to a human. A method of stimulating the immune system, and of treating immune system disorders, by treating blood with ultraviolet radiation and ozone gas, followed by administering the treated blood to a human. Also disclosed is a method of treating Raynaud's Disease by contacting about 0.01 ml to about 400 ml of human blood with a blood platelet aggregation-inhibiting effective amount of ozone gas in admixture with oxygen gas, and ultraviolet radiation, while maintained at a temperature in the range of from about 37.degree. C. to about 43.degree. C. for a period for about 0.5 minutes to about 10 minutes, and administering the blood so treated to a human patient with Raynaud's Disease.

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Tideswell, United Kingdom

Anthony E Bolton