US4764504A
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Novel atrial natriuretic/vasodilator polypeptides
Assignee: Scios LLC
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Filing: 1985-04-16
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Granted: 1988-08-16
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Expires: 2005-04-16
Abstract
Abstract Methods and compositions are provided for inducing natriuresis, diuresis and vasodilatation in mammalian hosts by administering atrial natriuretic/vasodilator polypeptides to said host. Also provided are methods for producing such polypeptides, and antibodies which are capable of recognizing and specifically binding to them.
Inventors
- 👤 Lorin K. Johnson
- 👤 Steven A. Atlas
- 👤 Brian J. McCarthy
- 👤 John H. Laragh
- 👤 John A. Lewicki
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 14:14
CPC Classifications
C; C12; C12N; C12N15/00; C12N15/09; C12N15/11; C12N15/62; C12N15/625; C07; C07K; C07K14/00; C07K14/435; C07K14/575; C07K14/58; C07K14/582; C12N15/63; C12N15/70; C12N15/79; C12N15/80; C12N15/81; C12N15/85; A; A61; A61K; A61K38/00; C07K2319/00; C07K2319/01; C07K2319/02; C07K2319/036; C07K2319/50; C07K2319/70; C07K2319/74; C07K2319/75
Claims Analysis
Total Claims: 5
Claim 1
Independent Claim
228 words
A polypeptide compound useful as a natriuretic, diuretic, and/or vasodilator in mammals, said polypeptide compound having the formula: ##STR33## wherein X is hydrogen, amido, acetyl, or an oligopeptide of up to 125 amino acid residues from the naturally occurring N-terminal Atrial Peptide Sequence, including the N-acetyl derivatives thereof; Y is hydroxyl, amido, Asn-OH, Asn-Ser-OH, Asn-Ser-Phe-OH, Asn-Ser-Phe-Arg-OH, Asn-Ser-Phe-Arg-Tyr-OH, or the C-terminal amide derivatives thereof; or an oligopeptide extension of up to 20 amino acid residues from the C-terminus of any of the foregoing, including the C-terminal amide derivatives thereof; each of AA 6 , AA 7 , AA 13 , and AA 17 is independently selected from the group consisting of Gly and Ala; AA 9 is selected from Ile, Met, and Val; and AA 12 is selected from Ile and Val, wherein 0, 1 or 2 are by the D-isomer thereof, and including such compound containing a disulfide bridge joining the cysteine residues and the pharmacologically acceptable salts thereof, with the proviso that when AA 6 , AA 7 , AA 13 , and AA 17 are Gly, AA 9 is Ile or Met, AA 12 is Ile, and Y is AsnOH, Asn-Ser-OH, Asn-Ser-Phe-OH, Asn-Ser-Phe-Arg-OH or Asn-Ser-Phe-Arg-Try-OH or the C-terminal amide derivatives thereof, and X is H or contains Arg as its C-terminal amino acid, at least one of the residues must be replaced by the D-isomer thereof.
Claim 2
Dependent Claim
228 words
A polypeptide compound useful as a natriuretic, diuretic, and/or vasodilator in mammals, said polypeptide compound having the formula: ##STR33## wherein X is hydrogen, amido, acetyl, or an oligopeptide of up to 125 amino acid residues from the naturally occurring N-terminal Atrial Peptide Sequence, including the N-acetyl derivatives thereof; Y is hydroxyl, amido, Asn-OH, Asn-Ser-OH, Asn-Ser-Phe-OH, Asn-Ser-Phe-Arg-OH, Asn-Ser-Phe-Arg-Tyr-OH, or the C-terminal amide derivatives thereof; or an oligopeptide extension of up to 20 amino acid residues from the C-terminus of any of the foregoing, including the C-terminal amide derivatives thereof; each of AA 6 , AA 7 , AA 13 , and AA 17 is independently selected from the group consisting of Gly and Ala; AA 9 is selected from Ile, Met, and Val; and AA 12 is selected from Ile and Val, wherein 0, 1 or 2 are by the D-isomer thereof, and including such compound containing a disulfide bridge joining the cysteine residues and the pharmacologically acceptable salts thereof, with the proviso that when AA 6 , AA 7 , AA 13 , and AA 17 are Gly, AA 9 is Ile or Met, AA 12 is Ile, and Y is AsnOH, Asn-Ser-OH, Asn-Ser-Phe-OH, Asn-Ser-Phe-Arg-OH or Asn-Ser-Phe-Arg-Try-OH or the C-terminal amide derivatives thereof, and X is H or contains Arg as its C-terminal amino acid, at least one of the residues must be replaced by the D-isomer thereof.
Claim 3
Dependent Claim
50 words
A polypeptide compound in accordance with claim 1 wherein the compound is selected from the group consisting of: H-Arg-Ser-Ser-Cye-Phe-Gly-Gly-Arg-(D-Met)-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH H-Arg-Ser-Ser-(D-Cys)-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH H-Arg-Ser-Ser-Cys-(D-Phe)-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH H-Arg-Ser-Ser-Cys-Phe-(D-Ala)-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH H-Arg-Ser-Ser-Cys-Phe-Gly-(D-Ala)-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-(D-Arg)-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-(D-Val)-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-(D-Arg)-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-(D-Val)-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-(D-Ala)-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-(D-Ala)-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-(D-Gln)-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-(D-Ser)-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-(D-Ala)-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH H-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-(D-Leu)-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH including such compound containing a disulfide bridge joining the cysteine residues, and the pharmacologically acceptable salts thereof.
Claim 4
Dependent Claim
27 words
A pharmaceutical composition comprising a polypeptide compound in accordance with any of claims 1 or 2 in a therapeutically effective amount, together with a physiologically suitable carrier.
Claim 5
Independent Claim
42 words
A method for inducing natriuresis, diuresis, vasodilatation, inhibiting renin secretion or modulating angiotensin-induced aldosterone release in a mammalian host, which comprises administering to said host a pharmaceutically effective amount of the compound or composition of any of claims 1, 2 or 3.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1991-08-16 | 1992-02-15 | 1992-08-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-08-16 | 1996-02-15 | 1996-08-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-08-16 | 2000-02-15 | 2000-08-16 | $7700.00 | Window Closed / Lapsed |