Other

W2 Holdings, Inc.

Talaria Therapeutics, Inc.

Thomas Jefferson University

Columbia University

Esperion Luv Development, Inc.

Reverse Transport Licensing & Consulting, Inc.

Kevin Jon Williams

Ira A Tabas

Scott L Schissel

Michael J Hope

Wendi Rodrigueza

The invention relates to thrombospondin fragments found in plasma, their use or use of portions thereof in diagnostic methods, as method calibrators, method indicators, and as immunogens, and as analytes for methods with substantial clinical utility; and their detection in plasma or other bodily fluids for purpose of diagnostic methods, especially for cancer.

Thrombospondin fragments and binding agents in the detection, diagnosis and evaluation of cancer

Clinical assays for thrombospondin fragments in the detection, diagnosis, and evaluation of cancer

The present invention provides a liposomal composition for treating dislipidemias in human subjects, a method of using a liposomal composition, and devices and modes of operation of the devices and of the compositions, and kits related thereto. The invention provides for the reverse transport of cholesterol from peripheral tissues to the liver in a warm blood mammal while controlling plasma atherogenic lipoprotein concentrations, including LDL concentrations. A method described above and mode of operation of the devices includes the stop of administering an effective amount of a multiplicity of acceptors comprised of phospholipids substantially free of sterol. A method described above optionally includes the stop of periodically assaying atherogenic lipoprotein concentrations with an assay during the treatment period to assess atherogenic lipoprotein concentrations and obtain an atherogenic lipoprotein profile.

Liposomal compositions, and methods of using liposomal compositions to treat dislipidemias

The present invention provides for a method for treating a subject suffering from a condition associated with an extracellular zinc sphingomyelinase activity which comprises administering to the subject an amount of a zinc sphingomyelinase inhibitor effective to decrease extracellular zinc sphingomyelinase activity in the subject and thereby treat the subject. The present invention also provides for a method for determining whether a compound inhibits an activity of an extracellular zinc sphingomyelinase involving ceramide formation which comprises: (a) contacting a sample containing zinc sphingomyelinase under acidic pH conditions known to be associated with the activity of such zinc sphingomyelinase, with: (i) a substrate of the zinc sphingomyelinase enzyme, and (ii) the compound being evaluated; (b) measuring the ceramide in the sample from (a); (c) determining the amount of zinc sphingomyelinase activity in the sample based on the concentration of ceramide measured in step (b); and (d) comparing the amount of sphingomyelinase activity determined in step (c) with the amount of sphingomyelinase activity determined in the absence of the compound, so as to determine whether the compound inhibits the activity of zinc sphingomyelinase.

Method for treating a subject suffering from conditions associated with an extracellular zinc sphingomyelinase

Genes and polypeptides encoded thereby of human chondroitin 6-sulfotransferase are provided. Vectors and host cells comprising these genes and transgenic animals capable of expressing them are also provided. In addition, methods of identifying polymorphic chondroitin 6-sulfotransferase in humans and activators or inhibitors of this enzyme are provided.

Human gene encoding human chondroitin 6-sulfotransferase

The present invention provides a pharmaceutical composition, kit, and method of forcing the reverse transport of cholesterol from peripheral tissues to the liver in vivo while controlling plasma LDL concentrations. The method includes the step of administering a therapeutically effective amount of a multiplicity of large liposomes comprised of phospholipids substantially free of sterol for a treatment period. The method optionally includes the step of periodically assaying plasma LDL concentrations with an assay during the treatment period to assess plasma atherogenic lipoprotein concentrations and obtain an atherogenic lipoprotein profile, and adjusting the administration in response to said profile. The large liposomes are dimensioned larger than fenestrations of an endothelial layer lining hepatic sinusoids in the liver so that the liposomes are too large to readily penetrate the fenestrations. The therapeutically effective amounts are in the range of about 10 mg to about 1600 mg phospholipid per kg body weight per dose. A pharmaceutical composition and related kit for mobilizing peripheral cholesterol and sphingomyelin that enters the liver of a subject consisting essentially of liposomes of a size and shape larger than fenestrations of an endothelial layer lining hepatic sinusoids in the liver is also provided.

METHOD OF FORCING THE REVERSE TRANSPORT OF CHOLESTEROL FROM A BODY PART TO THE LIVER WHILE AVOIDING HARMFUL DISRUPTIONS OF HEPATIC CHOLESTEROL HOMEOSTASIS, AND PHARMACEUTICAL COMPOSITIONS AND KIT RELATED THERETO

A pharmaceutical composition, kit, and method of forcing the reverse transport of cholesterol from peripheral tissues to the liver in vivo while controlling plasma LDL concentrations. The method includes the step of administering a therapeutically effective amount of a multiplicity of large liposomes comprised of phospholipids substantially free of sterol for a treatment period. The method optionally includes the step of periodically assaying plasma LDL concentrations with an assay during the treatment period to assess plasma atherogenic lipoprotein concentrations and obtain an atherogenic lipoprotein profile, and adjusting the administration in response to said profile. The large liposomes are dimensioned larger than fenestrations of an endothelial layer lining hepatic sinusoids in the liver so that the liposomes are too large to readily penetrate the fenestrations. The therapeutically effective amounts are in the range of about 10 mg to about 1600 mg phospholipid per kg body weight per dose. A pharmaceutical composition and related kit for mobilizing peripheral cholesterol and sphingomyelin that enters the liver of a subject consisting essentially of liposomes of a size and shape larger than fenestrations of an endothelial layer lining hepatic sinusoids in the liver is also provided.

Method of forcing the reverse transport of cholesterol from a body part

The present invention provides an improved mode of operation of an apparatus for angioplasty or cardiac catheterization, apparatus for angioplasty and cardiac catheterization, and method of angioplasty or cardiac catheterization. The improvement and improved mode of operation includes the step of administering a therapeutically effective amount of a lipid acceptor during angioplasty or cardiac catheterization of a subject with the apparatus or component thereof. The lipid acceptor is selected from the group consisting of a large liposome comprised of phospholipids substantially free of sterol and small acceptors. The effective period of time is in the range of about less than 1 minute to about two years from the time of the angioplasty or cardiac catheterization. The improved angioplasty or cardiac catheterization apparatus includes means for administering a therapeutically effective amount of a lipid acceptor, and optional co-administration means for administering the lipid acceptor and a diagnostic agent. The improved mode of operating an angioplasty or cardiac catheterization apparatus includes administering a therapeutically effective amount of a lipid acceptor from the apparatus or component thereof into a vessel of a subject by administration means. The invention further provides a method of diagnosing a side-effect of reverse transport of cholesterol from peripheral tissues to the liver in vivo accompanying parenteral administration of a multiplicity of large liposomes and small liposomes during a treatment period. The method includes the step of periodically assaying plasma atherogenic lipoprotein concentrations with an assay to obtain an assayed atherogenic lipoprotein concentration.

Methods of angioplasty and cardiac catheterization

The present invention provides for a method for treating a subject suffering from a condition associated with an extracellular zinc sphingomyelinase activity which comprises administering to the subject an amount of a zinc sphingmyelinase inhibitor effective to decrease extracellular zinc sphingomyelinase activity in the subject and thereby treat the subject. The present invention also provides for a method for determining whether a compound inhibits an activity of an extracellular zinc sphingomyelinase involving ceramide formation which comprises: (a) contacting a sample containing the zinc sphingomyelinase under acidic pH conditions known to be associated with the activity of such zinc sphingomyelinase, with: (i) a substrate of the zinc sphingomyelinase enzyme, and (ii) the compound being evaluated; (b) measuring the concentration of ceramide in the sample from (a); (c) determining the amount of zinc sphingomyelinase activity in the sample based upon the concentration of ceramide measured in step (b); and (d) comparing the amount of sphingomyelinase activity determined in step (c) with the amount of sphingomyelinase activity determined in the absence of the compound, so as to determine whether the compound inhibits the activity of zinc sphingomyelinase.

Method for treating a subject suffering from a condition associated with

A method of regulating cholesterol related genes, enzymes and other compounds, pharmaceutical compositions and a kit related thereto are provided. Exemplary genes that are regulated include a gene for an LDL receptor, a gene for HMG-CoA reductase, a gene for cholesterol 7-alpha-hydroxylase, and a gene regulating a function involved in cholesterol homeostasis. The method comprises the step of parenterally administering a therapeutically effective amount of a lipid acceptor. The lipid acceptor in one variant includes a multiplicity of large liposomes comprised of phospholipids substantially free of sterol during a treatment period. The method includes the steps of periodically assaying plasma LDL concentrations with an assay during a period of time to assess the plasma LDL and to obtain an LDL profile, and adjusting the parenteral administration in response to the LDL profile. The method further includes the step of enhancing tissue penetration of a cholesterol acceptor and enhancing extraction of tissue cholesterol and other exchangeable material with co-administration of an effective amount of a compound selected from the group consisting of a small acceptor of cholesterol, an amphipathic compound, and a drug that increases endogenous small acceptors of cholesterol.

Methods of regulating CETP genes, enzymes and other compound, and

The present invention provides compositions for, a method of suppressing the rise in plasma concentrations of atherogenic lipoproteins after administration of an agent having small acceptors of cholesterol, other lipids or compounds. The method includes the step of co-administering an effective amount of a multiplicity of an agent having large liposomes that include phospholipids substantially free of sterol with the administration of the agent having the small acceptors. The atherogenic lipoproteins include LDL, VLDL, IDL, .beta.-VLDL, Lp(a), a lipoprotein containing apolipoprotein-B, oxidized lipoproteins, and modified lipoproteins. The agent having small acceptors consists essentially of small acceptors and in which the agent having large liposomes consists essentially of large liposomes. In a variant, co-administration of the agent having large liposomes is simultaneous with the administration of the agent having small acceptors. Optionally, co-administration of the agent having large liposomes is separated in time from the administration of the agent having small acceptors by an effective time period. An improved pharmaceutical composition for reducing the size of arterial lesions that enters the liver of a subject is also provided the improvement comprises an anti-oxidant and derivatives thereof. The invention also provides an improved mode of operation of liposomes utilizing the improvements described herein.

Method of suppressing a rise in LDL concentrations after administration

The present invention provides an improved dialysis apparatus for the treatment of a patient, improved mode of operation of a dialysis apparatus and improved method of dialysis. The improvement includes means for administering a therapeutically effective amount of a lipid acceptor during the treatment of a subject, and actuation of the means during operation of the dialysis apparatus. The lipid acceptor is selected from the group consisting of a multiplicity of large liposomes comprised of phospholipids substantially free of sterol and small acceptors. The means for administering said agent is selected from the group consisting of means for extracorporeal administration and means for intracorporal administration. The dialysis includes hemodialysis, peritoneal dialysis, and rectal dialysis, and the agent is added directly to blood or blood plasma of a subject in one variant.

Method of dialysis treatment, and dialysis apparatus related thereto

A pharmaceutical composition, kit, and method of forcing the reverse transport of cholesterol from peripheral tissues to the liver in vivo while controlling plasma LDL concentrations is provided. The method includes the step of administering a therapeutically effective amount of a multiplicity of large liposomes comprised of phospholipids substantially free of sterol for a treatment period. The method optionally includes the step of periodically assaying plasma LDL concentrations with an assay during the treatment period to assess plasma atherogenic lipoprotein concentrations and obtain an atherogenic lipoprotein profile, and adjusting the administration in response to the profile. The large liposomes are dimensioned larger than fenestrations of an endothelial layer lining hepatic sinusoids in the liver so that the liposomes are too large to readily penetrate the fenestrations. The therapeutically effective amounts are in the range of about 10 mg to about 1600 mg phospholipid per kg body weight per dose. A pharmaceutical composition and related kit for mobilizing peripheral cholesterol and sphingomyelin that enters the liver of a subject consisting essentially of liposomes of a size and shape larger than fenestrations of an endothelial layer lining hepatic sinusoids in the liver is also provided.

A method of regulating cholesterol related genes, enzymes and other compounds, pharmaceutical compositions and a kit related thereto are provided. Exemplary genes that are regulated include a gene for an LDL receptor, a gene for HMG-CoA reductase, a gene for cholesterol 7-alpha-hydroxylase, and a gene regulating a function involved in cholesterol homeostasis. The method comprises the step of parentorally administering a therapeutically effective amount of a lipid acceptor. The lipid acceptor in one variant includes a multiplicity of large liposomes comprised of phospholipids substantially free of sterol during a treatment period. The method includes the steps of periodically assaying plasma LDL concentrations with an assay during a period of time to assess said plasma LDL and to obtain an LDL profile, and adjusting the parenteral administration in response to the LDL profile. The method further includes the step of enhancing tissue penetration of a cholesterol acceptor and enhancing extraction of tissue cholesterol and other exchangeable material with co-administration of an effective amount of a compound selected from the group consisting of a small acceptor of cholesterol, an amphipathic compound, and a drug that increases endogenous small acceptors of cholesterol.

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Wynnewood, PA, United States of America

Kevin Jon Williams