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Details for Patent: 6,586,396

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Details for Patent: 6,586,396

Title: Subcutaneous administration of natriuretic peptide
Abstract:The cDNA sequence encoding porcine brain natriuretic peptide and related genes encoding canine and human peptides with natriuretic activity are disclosed. The gene is shown to make accessible the DNAs encoding analogous natriuretic peptides in other vertebrate species. The genes encoding these NPs can be used to effect modifications of the sequence to produce alternate forms of the NPs and to provide practical amounts of these proteins. The NPs of the invention can also be synthesized chemically. The invention peptides have the formula: wherein R.sup.1 is selected from the group consisting of: or a 10- to 109-amino acid sequence shown as the native upstream sequence for porcine, canine or human BNP in FIG. 8, or a composite thereof; R.sup.2 is (OH), NH.sub.2, or NR'R" wherein R' and R" are independently lower alkyl (1-4C) or is and R.sup.1 is Asp-Ser-Gly-, R.sup.2 cannot be Asn-Val-Leu-Arg-Arg-Tyr. The peptides of the invention can be formulated into pharmaceutical compositions and used to treat conditions associated with high extracellular fluid levels, especially congestive heart failure.
Inventor(s): Seilhamer; J. Jeffrey (Milpitas, CA), Lewicki; John (San Jose, CA), Scarborough; Robert M. (Hayward, CA), Porter; J. Gordon (Newark, CA)
Assignee: Scios, Inc. (Sunnyvale, CA)
Filing Date:Apr 07, 1999
Application Number:09/287,892
Claims:1. A method to treat a subject in need of such treatment with a peptide having natriuretic activity which method comprises administering said peptide subcutaneously to said subject, wherein said peptide comprises human or canine brain natriuretic peptide.

2. The method of claim 1 wherein said subject is a human and the peptide is of the formula: R.sup.1 -Cys-Phe-Gly-Arg-Lys-Met-Asp-Arg-Ile-Ser-Ser-Ser-Ser-Gly-Leu-Gly-Cys-R. sup.2 wherein Ris selected from the group consisting of:

3. The method of claim 2 wherein the peptide is of the formula: Ser-Pro-Lys-Met-Val-Gln-Gly-Ser-Gly-Cys-Phe-Gly-Arg-Lys-Met-Asp-Arg-Ile-Ser -Ser-Ser-Ser-Gly-Leu-Gly-Cys-Lys-Val-Leu-Arg-Arg-His, or the C-terminal amides thereof.

4. The method of claim 2 wherein said natriuretic peptide is admixed with at least one pharmaceutically acceptable excipient.

5. The method of claim 1 wherein the subject is a canine and the peptide with natriuretic activity is of the formula: R.sup.1 -Cys-Phe-Gly-Arg-Arg-Leu-Asp-Arg-Ile-Gly-Ser-Leu-Ser-Gly-Leu-Gly-Cys-R. sup.2 wherein R.sup.1 is selected from the group consisting of:

6. A method to treat a subject for a condition characterized by an abnormally high extracellular fluid level which method comprises administering subcutaneously to said subject a peptide having natriuretic activity, wherein said peptide comprises human or canine brain natriuretic peptide.

7. The method of claim 6 wherein said subject is a human and the peptide is of the formula: R.sup.1 -Cys-Phe-Gly-Arg-Lys-Met-Asp-Arg-Ile-Ser-Ser-Ser-Ser-Gly-Leu-Gly-Cys-R. sup.2 wherein R.sup.1 is selected from the group consisting of:

8. The method of claim 6 wherein the peptide is of the formula: Ser-Pro-Lys-Met-Val-Gln-Gly-Ser-Gly-Cys-Phe-Gly-Arg-Lys-Met-Asp-Arg-Ile-Ser -Ser-Ser-Ser-Gly-Leu-Gly-Cys-Lys-Val-Leu-Arg-Arg-His, or the C-terminal amides thereof.

9. The method of claim 6 wherein said natriuretic peptide is admixed with at least one pharmaceutically acceptable excipient.

10. The method of claim 6 wherein the subject is a canine and the peptide with natriuretic activity is of the formula: R.sup.1 -Cys-Phe-Gly-Arg-Arg-Leu-Asp-Arg-Ile-Gly-Ser-Leu-Ser-Gly-Leu-Gly-Cys-R. sup.2 wherein R.sup.1 is selected from the group consisting of:
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