Natriuretic compounds, conjugates, and uses thereof

Abstract

Modified natriuretic compounds and conjugates thereof are disclosed in the present invention. In particular, conjugated forms of hBNP are provided that include at least one modifying moiety attached thereto. The modified natriuretic compound conjugates retain activity for stimulating cGMP production, binding to NPR-A receptor, and in some embodiments an improved half-life in circulation as compared to unmodified counterpart natriuretic compounds. Oral, parenteral, enteral, subcutaneous, pulmonary, and intravenous forms of the compounds and conjugates may be prepared as treatments and/or therapies for heart conditions particularly congestive heart failure. Modifying moieties comprising oligomeric structures having a variety of lengths and configurations are also disclosed. Analogs of the natriuretic compound are also disclosed, having an amino acid sequence that is other than the native sequence.

Description

1. RELATED APPLICATIONS [0001] This application is based on and claims priority to, U.S. provisional patent application Ser. No. 60 / 574,436, filed May 26, 2004, pending, entitled “NATRIURETIC COMPOUNDS, CONJUGATES, AND USES THEREOF”. The entire disclosure of each of this application is incorporated here by reference in its entirety, and the benefit of the filing date of such patent application is hereby claimed for all purposes that are legally served by such claim2. STATEMENT OF GOVERNMENT SUPPORT [0002] The subject invention was made with government support under a research project supported by NIH Grant #1 R43 HL074529-01. The United States government has certain rights in this invention.3. FIELD OF THE INVENTION [0003] The present invention relates to the field of natriuretic compound conjugates and variant natriuretic compounds, and uses of these in the treatment of congestive heart disease and conditions related to this condition. For example, the compositions of the present i...

AI Technical Summary

Benefits of technology

[0015] The present invention broadly comprises variant and modified forms of several naturally occurring natriuretic peptides, proteins, analogs, and chemical conjugates of these natriuretic peptides that possess one or more advantages over their na

Problems solved by technology

This life-threatening condition is accompanied by great financial impact.

CHF is a common cause of death, is accompanied by high indirect costs for treatment, and has a high mortality rate.

Despite this increase, the beneficial effects of BNP are blunted in severe CHF, raising the possibility of a relative deficiency state in overt CHF.

Alternatively, as the assays currently employed to measure plasma concentration of BNP do not specifically differentiate between pre-pro BNP and the mature form, this pro-hormone may not be adequately processed to its mature form in overt CHF.

Therefore, either the amount of BNP that the heart can

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