Ischemia Technologies, Inc.

Other

Dmi Biosciences, Inc.

Edward Lau

David Bar-Or

James V Winkler

Nagaraja K R Rao

C Gerald Curtis

Gary Fagan

Hollie Wayment

Wannell M Crook

Nagaraja KR Rao

The invention provides a method of reducing the damage done by reactive oxygen species (ROS) in an animal. The invention also provides a method of reducing the concentration of a metal in an animal. These methods comprise administering to the animal an effective amount of a metal-binding compound as further described in the application. The invention further provides a method of reducing the damage done by ROS to a cell, a tissue or an organ that has been removed from an animal. This method comprising contacting the cell, tissue or organ with a solution or medium containing an effective amount of a metal-binding compound of the invention. The invention further provides novel metal-binding compounds, pharmaceutical compositions comprising the metal-binding compounds, and kits comprising a container holding a metal-binding compound of the invention.

Metal-binding compounds and uses therefor

The present invention teaches a marker useful for detection and measurement of free radical damage. Specifically, the invention takes advantage of alterations which occur to the N-terminus of the albumin molecule, a circulating protein in human blood, in the presence of free radicals. These alterations affect the ability of the N-terminus of the albumin molecule to bind metals. Methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of an albumin containing sample, analysis and measurement of the ability of albumin to bind exogenous cobalt, detection and measurement of the presence of copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following free radical damage. Also taught by the present invention is the use of the compound Asp-Ala-His-Lys-R (SEQ ID NO:1), wherein R is any chemical group capable of being detected when bound to any compound capable of binding to the N-terminus of naturally occurring albumin (including no additional chemical group), for detection and quantification of the marker. Methods of the present invention also include use of the marker as a 'biochemical tag,' thereby allowing for sensitive detection and measurement of the efficacy of clinical drugs and therapeutics which result in the generation of free radicals, such as Photofrin&#xae; (porfimer sodium), or which act to limit free-radical damage. The marker also acts as a 'biological tag' of a process implicated in a wide array of diseases and sequelae and, accordingly, may be used to test for the occurrence or non-occurrence of such diseases and sequelae. One such disease is ischemia.

Marker useful for detection and measurement of free radical damage and method

The present invention relates to rapid methods for the detection of ischemic states and to kits for use in such methods. Provided for is a rapid method of testing for and quantifying ischemia based upon methods of detecting and quantifying the existence of an alteration of the serum protein albumin which occurs following an ischemic event; methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of circulating albumin, analysis and measurement of the ability of serum albumin to bind exogenous cobalt, detection and measurement of the presence of endogenous copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following an ischemic event. Also taught by the present invention is the detection and measurement of an ischemic event by measuring albumin N-terminal derivatives that arise following an ischemic event, including truncated albumin species lacking one to four N-terminal amino acids or albumin with an acetylated N-terminal Asp residue.

Tests for the rapid evaluation of ischemic states and kits

The present invention teaches a marker useful for detection and measurement of free radical damage. Specifically, the invention takes advantage of alterations which occur to the N-terminus of the albumin molecule, a circulating protein in human blood, in the presence of free radicals. These alterations effect the ability of the N-terminus of the albumin molecule to bind metals. Methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of an albumin-containing sample, analysis and measurement of the ability of albumin to bind exogenous cobalt, detection and measurement of the presence of copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following free radical damage. Also taught by the present invention is the use of the peptide Asp Ala His Lys and the compound Asp-Ala-His-Lys-R, wherein R is any chemical group capable of producing a detectable signal when a metal ion capable of binding to the N-terminus of naturally-occurring albumin is bound to the compound, for detection and quantitation of the marker. Methods of the present invention also include use of the marker as a 'biochemical tag,' thereby allowing for sensitive detection and measurement of the efficacy of clinical drugs and therapeutics which result in the generation of free radicals or which act to limit free radical damage. The marker also acts as a 'biological tag' of a process implicated in a wide array of diseases and conditions and, accordingly, may be used to monitor and assess such diseases and conditions. Finally, the invention provides antibodies, immunoassays, and kits for use in detecting or quantitating the marker.

The present invention relates to a rapid method for the detection of ischemic states and to a kit for use in such a method. Provided for is a rapid method of testing for the existence of and quantifying ischemia based upon method of detecting and quantifying the existence of an alteration of the serum protein albumin which occurs following an ischemic event; methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of circulating blood, analysis and measurement of the ability of serum albumin to bind exogenous cobalt, detection and measurement of the presence of copper in a purified albumin sample and use of an immunological assay sepcific to the alterated form of serum albumin which occurs following an ischemic event. Also taught by the present invention is the use of the compound Asp-Ala-His-Lys-R, wherein R is any chemical group capable of being detected when bound to any compound capable of binding to the N-terminus of naturally occurring human albumin (including no additional chemical group), for detection and quantification of an ischemic event.

Test for rapid evaluation of ischemic states and kit

The present invention teaches a marker useful for detection and measurement of free radical damage. Specifically, the invention takes advantage of alterations which occur to the N-terminus of the albumin molecule, a circulating protein in human blood, in the presence of free radicals. These alterations effect the ability of the N-terminus of the albumin molecule to bind metals. Methods for detecting and quantifying this alteration include evaluating and quantifying the cobalt binding capacity of an albumin containing sample, analysis and measurement of the ability of albumin to bind exogenous cobalt, detection and measurement of the presence of copper in a purified albumin sample and use of an immunological assay specific to the altered form of serum albumin which occurs following free radical damage. Also taught by the present invention is the use of the compound Asp-Ala-His-Lys-R &lsqb;SEQ ID NO:1&rsqb;, wherein R is any chemical group capable of being detected when bound to any compound capable of binding to the N-terminus of naturally occurring albumin, for detection and quantification of the marker. Methods of the present invention also include use of the marker as a &ldquo;biochemical tag,&rdquo; thereby allowing for sensitive detection and measurement of the efficacy of clinical drugs and therapeutics.

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Boulder, CO, United States of America

Edward Lau