Compositions and methods for treating cardiovascular disease and myocardial infarction with dipeptidyl peptidase inhibitors or b type natriuretic peptide analogues resistant to prolyl-specific dipeptidyl degradation

Abstract

The present invention describes compositions and methods for treating cardiovascular disease and myocardial infarction using dipeptidyl peptidase inhibitors. Also provided are methods for increasing natriuretic peptide function by administering one or more analogues of B type natriuretic peptide that provide increased stability in the presence of prolyl-specific dipeptidyl peptidases.

Description

CROSS-REFERENCE[0001]This application is a continuation of U.S. patent application Ser. No. 12 / 391,157, filed on Feb. 23, 2009, which is a continuation of U.S. patent application Ser. No. 11 / 560,425, filed Nov. 16, 2006, which is a continuation of U.S. patent application Ser. No. 10 / 938,760, filed Sep. 9, 2004, now U.S. Pat. No. 7,524,635; which claims the benefit of U.S. Provisional Application No. 60 / 542,086, filed Feb. 4, 2004, and which is a continuation-in-part of U.S. patent application Ser. No. 10 / 645,874, filed Aug. 20, 2003, and Ser. No. 10 / 419,059, filed Apr. 17, 2003, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 835,298, filed Apr. 13, 2001, now U.S. Pat. No. 7,632,647, and Ser. No. 10 / 139,086, filed May 4, 2002, now U.S. Pat. No. 7,361,473, which claims the benefit of U.S. Provisional Application Nos. 60 / 315,642, filed Aug. 28, 2001, and 60 / 288,871, filed May 4, 2001; and U.S. patent application Ser. No. 10 / 419,059, filed Apr. 17, 2003, is a con...

AI Technical Summary

Benefits of technology

[0014]Failure to consider this degradation when designing an assay for one or more natriuretic peptides may result in an assay that detects both biologically active forms of a natriuretic peptide(s) of interest, as well as inactive fragments of the natriuretic peptide(s). This may lead to the conclusion that an assay shows particularly good stability (i.e., the analyte of interest is not lost to the assay during sample storage), when in fact the natriuretic peptide of interest is actually being degraded to an inactive fragment and the assay result is confounded by the inability to distinguish the intended analyte from the pool of inactive fragments originally present in the sample. Because the biologically active forms may be more relevant to the physiologic state of the subject, and because upregulated proteolytic enzymes in diseased subjects may lead to particularly large pools of inactive fragments in the subjects of potentially the greatest interest, the compositions and methods described herein may provide improved diagnostic and prognostic information to the artisan in comparison to assays that are not specific for the biologically active forms.

[0015]The methods and compositions described herein can meet the need in the art for rapid, sensitive and specific diagnostic assay to be used in the diagnosis and differentiation of various cardiovascular diseases, including stroke, congestive heart failure (CHF), cardiac ischemia, systemic hypertension, and / or acute myocardial infarction. Moreover, the methods and compositions of the present invention can also be used to facilitate the treatment of patients and the development of additional diagnostic and / or prognostic indicators and indicator panels.

Problems solved by technology

Failure to consider this degradation when designing an assay for one or more natriuretic peptides may result in an assay that detects both biologically active forms of a natriuretic peptide(s) of interest, as well as inactive fragments of the natriuretic peptide(s).

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