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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: 1 R1-Cys-Phe-Gly-Arg- Arg/ - Leu/ -Asp-Arg- Lys Met (1) Ile- Gly/ -Ser- Leu/ -Ser-Gly-Leu-Gly-Cys-R-2 Ser Ser wherein R1 is selected from the group consisting of: 2 (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 3 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 4 R1-Cys-Phe-Gly-Arg-Arg-Leu-Asp-Arg- Ile-Gly-Ser-Leu-Ser-Gly-Leu-Gly-Cys-R2 and R 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 peptide having natriuretic activity of the formula:
A DNA probe useful in retrieving the gene encoding brain natriuretic peptide from a vertebrate DNA library, which probe comprises the pBNP-encoding cDNA shown in FIG. 1, or an effective portion thereof.
A DNA sequence which comprises a segment of contiguous or non-contiguous portions of the cDNA of FIG. 1, which segment encodes a brain natriuretic peptide having natriuretic activity.
A DNA sequence which comprises a modified segment of contiguous or non-contiguous portions of the cDNA of FIG. 1 wherein said modified segment encodes a BNP having one or two conservative amino acid substitutions.
A brain natriuretic peptide which is a modification of a BNP encoded by a segment of contiguous or non-contiguous portions of the cDNA of FIG. 1 wherein one or two positions contain conservative amino acid substitutions.
Dependencies are inferred from the claim text.