Claims
- 1. A compound of formula (I):
- 2. The compound of claim 1 wherein X0 is a peptide of from 1 to 25 amino acid residues.
- 3. The compound of claim 1 wherein X0 is an amino acid sequence from the N-terminus of BNP.
- 4. The compound of claim 3 wherein X0 is SEQ ID NO: 7.
- 5. The compound of claim 1 wherein X0 is an amino acid sequence from the N-terminus of CNP.
- 6. The compound of claim 5 wherein X0 is SEQ ID NO: 8.
- 7. A compound which comprises a variant of SEQ ID NO: 3, wherein the variant has one or more amino acid substitutions selected from the group consisting of Pro to Gly; Ser to Thr; Thr to Ser; Arg to Lys; Gln or Asn; Ala to Val, Ile, or Leu; Leu to Nor, Ile, Val, Met, Ala, or Phe; Asp to Glu; and Asn to Gln, His, Lys or Arg.
- 8. The compound of claim 7 which does not include the sequence Glu-Val-Lys-Tyr-Asp-Pro-Cys-Phe-Gly-His-Lys-Ile-Asp-Arg-Ile-Asn-His-Val -Ser-Asn-Leu-Gly-Cys (SEQ ID NO: 11).
- 9. A compound which comprises a variant of SEQ ID NO: 3, wherein the variant has one or more amino acid substitutions selected from the group consisting of Ser to Thr; Thr to Ser; Arg to Lys; Gln or Asn; Ala to Val, Ile, or Leu; Leu to Nor, Ile, Val, Met, Ala, or Phe; Asp to Glu; and Asn to Gln, His, Lys or Arg.
- 10. The compound of claim 7 or 9 further comprising a heterologous peptide at the amino-terminus of the variant peptide.
- 11. The compound of claim 10 wherein the heterologous peptide is from brain natriuretic peptide.
- 12. The compound of claim 11 wherein the heterologous peptide is SEQ ID NO: 7.
- 13. The compound of claim 10 wherein the heterologous peptide is from C-type natriuretic peptide.
- 14. The compound of claim 13 wherein the heterologous peptide is SEQ ID NO: 8.
- 15. The compound of claim 1 or 7 which has a biological activity selected from the group consisting of vasodilation, natriuresis, diuresis and renin suppression.
- 16. A method for treating heart failure in a mammal, comprising: administering to the mammal an effective amount of the compound of claim 1 or 7 in a pharmaceutically acceptable delivery vehicle.
- 17. The method of claim 16 wherein the administration is local.
- 18. The method of claim 16 wherein the administration is systemic.
- 19. The method of claim 16 wherein the mammal is a human, rat, mouse, canine, bovine, equine, ovine, caprine, or feline.
- 20. The method of claim 16 wherein the administration is parenteral.
- 21. A composition useful as a natriuretic, diuretic, renin-suppressor or vasodilator comprising a therapeutically effective amount of the compound of claim 1, 7 or 9 with a pharmaceutically acceptable carrier.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. application Ser. No. 09/466,268, filed Dec. 17, 1999, the disclosure of which is incorporated by reference herein.
STATEMENT OF GOVERNMENT SUPPORT
[0002] The invention was made, at least in part, with a grant from the Government of the United States of America (grant R01 HL36634 from the National Institutes of Health). The Government may have certain rights in the invention.
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
09466268 |
Dec 1999 |
US |
Child |
10106806 |
Mar 2002 |
US |