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AssigneeScios, Inc.
InventorsJ. Jeffrey Seilhamer, John Lewicki, Robert M. Scarborough, J. Gordon Porter
Estimating the term…
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: R1-Cys-Phe-Gly-Arg-Arg-/-Leu/-Asp-Arg- (1) Lys Met Ile-Gly/-Ser-Leu/-Ser-Gly-Leu-Gly-Cys-R2 Ser Ser wherein R1 is selected from the group consisting of: (H); Gly-; Ser-Gly-; Asp/ Lys/ -Ser-Gly-; Gly Arg/ Asp/ His/ - Lys/ -Ser-Gly-; Gln Gly Arg/ Asp/ Met/ - His/ - Lys/ -Ser-Gly-; Val Gln Gly Arg/ Asp/ Thr/ -Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly Arg/ Asp/ Lys- Thr/ -Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly Arg/ Asp/ Pro-Lys- Thr/ -Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly Arg/ Asp/ Ser-Pro-Lys- Thr/ -Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly 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; R2 is (OH), NH2, or NR′R″ wherein R′ and R″ are independently lower alkyl (1-4C) or is Asn/ Lys Asn/ -Val Lys Asn/ -Val-Leu Lys Asn/ -Val-Leu-Arg Lys Asn/ -Val-Leu-Arg- Arg/ Lys Lys Asn/ -Val-Leu-Arg- Arg/ - Tyr/ Lys Lys His or the amides (NH2 or NR′R″) thereof, with the proviso that if formula (1) is R1-Cys-Phe-Gly-Arg-Arg-Leu-Asp-Arg- Ile-Gly-Ser-Leu-Ser-Gly-Leu-Gly-Cys-R2 and R1 is Asp-Ser-Gly-, R2 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.
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.
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.
Dependencies are inferred from the claim text.