Bna Conjugates and Methods of Use
First Claim
1. A BNP compound conjugate comprising:
- a BNP molecule;
and at least one modifying moiety conjugated to the BNP molecule,wherein the BNP compound conjugate exhibits increased cGMP activity levels relative to a corresponding unconjugated BNP molecule.
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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, decreasing arterial blood pressure 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 hBNP compound are also disclosed, having an amino acid sequence that is other than the native sequence.
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Citations
43 Claims
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1. A BNP compound conjugate comprising:
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a BNP molecule; and at least one modifying moiety conjugated to the BNP molecule, wherein the BNP compound conjugate exhibits increased cGMP activity levels relative to a corresponding unconjugated BNP molecule. - View Dependent Claims (2, 3, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 21, 22, 23, 24)
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4. (canceled)
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16-20. -20. (canceled)
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25. A in vivo method for increasing cGMP activity and/or reducing arterial pressure, the method comprising administering to a subject a BNP compound conjugate comprising:
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a BNP molecule; and at least one modifying moiety conjugated to the BNP molecule, in an amount sufficient to increase cGMP activity and/or reduce arterial pressure. - View Dependent Claims (26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 43)
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37-42. -42. (canceled)
Specification