Biomarkers and assays for myocardial infarction

Abstract

Presented herein are novel blood plasma / serum biomarkers related to cardiovascular disease. These newly identified biomarkers create the basis for multiple (single) assays using traditional bioassay technologies and when used in combination yield exceptional clinical sensitivity and specificity in the determination of myocardial infarction (MI). A multiplexed, mass spectrometric immunoassay (MSIA) able to simultaneously assay for the new / novel biomarkers as well other MI markers is also presented. Means and methods for evaluating data generated using multiple biomarkers in order to validate findings and further the use of the multiplexed MI assay in clinical, diagnostic and therapeuatic uses is also included.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application No. 60 / 593,614, filed Jan. 28, 2005 which is herein incorporated by reference in its entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT [0002] Financial assistance for this project was provided by the U.S. Government through the National Institutes of Health under Grant Numbers 5 R44 CA99117-03 and 5 R44 HL072671-03; and the United States Government may own certain rights to this invention.FIELD OF INVENTION [0003] The present invention relates to new and novel blood plasma / serum biomarkers, which yield exceptional clinical sensitivity and specificity in the determination of cardiovascular diseases, and particularly in the determination of myocardial infarction (MI). According to the present invention, these new biomarkers are discovered and identified in MI-affected individuals and validated in larger cohorts of individuals suffering from MI. The ...

AI Technical Summary

Benefits of technology

[0014] Another object of the present invention is to improve upon the predictive accuracy of existing MI markers for the determination, diagnosis and monitoring of MI by using data from the analysis of SAA or TTR (and their variants).

[0015] It is yet another object of the present invention to improve upon the accuracy of analyzing myoglobin for the determination, diagnosis and monitoring of MI by using data from the analysis of SAA or TTR (and their variants).

[0019] The present invention describes the discovery and identification of new biomarkers able to determine, diagnose and monitor for cardiovascular diseases including MI. Moreover, the present invention is shown to improve the accuracy of MI determination by monitoring signal responses of SAA or TTR (and their variants) as present in blood plasma or serum. This methodology is even further improved when data from the two new biomarkers are used in combination with a conventional MI marker, myoglobin. Furthermore, the present invention describes a preferred mass spectrometry-based assay able to simultaneously detect the selected biomarkers and data analysis methods that, when applied to the resulting data, result in the improved determination of MI. The novel features that are considered characteristic of the invention are set forth with particularity in the appended claims. The invention itself, however, both as to its structure and its operation together with the additional objects and advantages thereof will best be understood from the following description of the preferred embodiment of the present invention when read in conjunction with the accompanying drawings. Unless specifically noted, it is intended that the words and phrases in the specification and claims be given the ordinary and accustomed meaning to those of ordinary skill in the applicable art or arts. If any other meaning is intended, the specification will specifically state that a special meaning is being applied to a word or phrase. Likewise, the use of the words “function” or “means” in the Description of Preferred Embodiments is not intended to indicate a desire to invoke the special provision of 35 U.S.C. §112, paragraph 6 to define the invention. To the contrary, if the provisions of 35 U.S.C. §112, paragraph 6, are sought to be invoked to define the invention(s), the claims will specifically state the phrases “means for” or “step for” and a function, without also reciting in such phrases any structure, material, or act in support of the function. Even when the claims recite a “means for” or “step for” performing a function, if they also recite any structure, material or acts in support of that means of step, then the intention is not to invoke the provisions of 35 U.S.C. §112, paragraph 6. Moreover, even if the provisions of 35 U.S.C. §112, paragraph 6, are invoked to define the inventions, it is intended that the inventions not be limited only to the specific structure, material or acts that are described in the preferred embodiments, but in addition, include any and all structures, materials or acts that perform the claimed function, along with any and all known or later-developed equivalent structures, materials or acts for performing the claimed function.

Problems solved by technology

However, it is accurate to state that the predictive metrics of the conventional MI markers are far from perfect, regardless of whether used individually or in various combinations.

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