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Details for Patent: 5,948,761

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Details for Patent: 5,948,761

Title: Recombinant canine brain natriuretic peptide
Abstract:Peptides 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: (H); Gly-; Ser-Gly-; Lys-Ser-Gly-; His-Lys-Ser-Gly-; Met-His-Lys-Ser-Gly-; Thr-Met-His-Lys-Ser-Gly-; Lys-Thr-Met-His-Lys-Ser-Gly-; Pro-Lys-Thr-Met-His-Lys-Ser-Gly-; Ser-Pro-Lys-Thr-Met-His-Lys-Ser-Gly-; or is the amino acid sequence of the dog prepro sequence upstream of position 100 shown in FIG. 8 herein or a C-terminal portion thereof; R.sup.2 is (OH), NH.sub.2, or NR.sub.2 wherein each R is independently H or lower alkyl (1-4C) or is Asn; Asn-Val; Asn-Val-Leu; Asn-Val-Leu-Arg; Asn-Val-Leu-Arg-Lys; Asn-Val-Leu-Arg-Lys-Tyr; or the amides thereof are useful in treating conditions characterized by high levels of extracellular fluid.
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. (Mountain View, CA)
Filing Date:May 05, 1997
Application Number:08/850,910
Claims:1. A peptide having natriuretic activity of the formula (SEQ ID NO: 15) 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 (SEQ ID NOs:6-11) is selected from the group consisting of:

(H);

Gly-;

Ser-Gly-;

Lys-Ser-Gly-;

His-Lys-Ser-Gly-;

Met-His-Lys-Ser-Gly-;

Thr-Met-His-Lys-Ser-Gly-;

Lys-Thr-Met-His-Lys-Ser-Gly-;

Pro-Lys-Thr-Met-His-Lys-Ser-Gly-;

Ser-Pro-Lys-Thr-Met-His-Lys-Ser-Gly-;

or is the amino acid sequence of the dog prepro sequence (SEQ ID NO: 47) upstream of position or a C-terminal portion thereof;

R.sup.2 (SEQ ID NOs: 12, 49-50) is (OH), NH.sub.2, or NR.sub.2 wherein each R is independently H or lower alkyl (1-4C) or is

Asn;

Asn-Val;

Asn-Val-Leu;

Asn-Val-Leu-Arg;

Asn-Val-Leu-Arg-Lys;

Asn-Val-Leu-Arg-Lys-Tyr;

or the amides thereof.

2. The peptide of claim 1 wherein R.sup.1 is Ser-Pro-Lys-Thr-Met-His-Lys-Ser-Gly-(SEQ ID NO: 11) and wherein R.sup.2 is Asn-Val-Leu-Arg-Lys-Tyr(SEQ ID NO: 50).

3. A recombinant DNA in isolated form which comprises a nucleotide sequence that encodes the peptide of claim 1.

4. A recombinant DNA in isolated form which comprises a nucleotide sequence that encodes the peptide of claim 2.

5. A recombinant expression system capable, when contained in a recombinant host cell, of expressing a nucleotide sequence encoding the peptide of claim 1, said expression system comprising said encoding nucleotide sequence operably linked to control sequences to effect its expression.

6. A recombinant expression system capable, when contained in a recombinant host cell, of expressing a nucleotide sequence encoding the peptide of claim 2, said expression system comprising said encoding nucleotide sequence operably linked to control sequences to effect its expression.

7. A recombinant host cell or cell culture which has been manipulated to contain the expression system of claim 6.

8. A recombinant host cell or cell culture which has been manipulated to contain the expression system of claim 7.

9. A method to produce a peptide having natriuretic activity which method comprises culturing the cells of claim 8 under conditions which permit the expression of the nucleotide sequence encoding the peptide.

10. A method to produce a peptide having natriuretic activity which method comprises culturing the cells of claim 8 under conditions which permit the expression of the nucleotide sequence encoding the peptide.

11. A pharmaceutical or veterinary composition useful in treating conditions associated with a high level of extracellular fluid which composition comprises an effective amount of the peptide of claim 1 in admixture with a suitable excipient.

12. A pharmaceutical or veterinary composition useful in treating conditions associated with a high level of extracellular fluid which composition comprises an effective amount of the peptide of claim 2 in admixture with a suitable excipient.

13. A method to treat a condition characterized by a high level of extracellular fluid which comprises administering to a subject in need of such treatment an effective amount of the peptide of claim 1 or a formulation thereof.

14. A method to treat a condition characterized by a high level of extracellular fluid which comprises administering to a subject in need of such treatment an effective amount of the peptide of claim 2 or a formulation thereof.
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