US4444759A
Expired / Lapsed
US
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GnRH Antagonists II
Assignee: Salk Institute for Biological Studies
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Filing: 1982-07-26
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Granted: 1984-04-24
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Expires: 2002-07-26
Abstract
Abstract Peptides which inhibit the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount prevents ovulation of female mammalian eggs and/or the release of steroids by the gondads. The peptides have the structure. X-β-D-2NAL-R 2 -D-Trp-Ser-R 5 -R 6 -R 7 -Arg-Pro-R 10 wherein X is hydrogen or an acyl group having 7 or less carbon atoms; R 2 is Cl-D-Phe, F-D-Phe, NO 2 -D-Phe, Cl 2 -D-Phe or Br-D-Phe; R 5 is Tyr or Cl-Phe; R 6 is 4-NH 2 -D-Phe or D-Arg; R 7 is Leu or NαMe-Leu; and R 10 is Gly-NH 2 , NHCH 2 CH 3 or D-Ala-NH 2 .
Inventors
- 👤 Jean E. F. Rivier
- 👤 Wylie W. Vale, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 21:30
CPC Classifications
C; C07; C07K; C07K7/00; C07K7/04; C07K7/06; C07K7/23; A; A61; A61K; A61K38/00; A61K38/04; A61K38/08; A61K38/09; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/13
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
79 words
A peptide or a nontoxic salt thereof, said peptide having the formula: X-β-D-2NAL-R.sub.2 -D-Trp-Ser-R.sub.5 -R.sub.6 -R.sub.7 -Arg-Pro-R.sub.10 wherein X is hydrogen or an acyl group having 7 or less carbon atoms; R 2 is Cl-D-Phe, F-D-Phe, NO 2 -D-Phe, Cl 2 -D-Phe or Br-D-Phe; R 5 is Tyr or 2-Cl-Phe; R 6 is 4-NH 2 -D-Phe or D-Arg; R 7 is Leu or NαMe-Leu; and R 10 is Gly-NH 2 , NHCH 2 CH 3 or D-Ala-NH 2 .
Claim 2
Dependent Claim
79 words
A peptide or a nontoxic salt thereof, said peptide having the formula: X-β-D-2NAL-R.sub.2 -D-Trp-Ser-R.sub.5 -R.sub.6 -R.sub.7 -Arg-Pro-R.sub.10 wherein X is hydrogen or an acyl group having 7 or less carbon atoms; R 2 is Cl-D-Phe, F-D-Phe, NO 2 -D-Phe, Cl 2 -D-Phe or Br-D-Phe; R 5 is Tyr or 2-Cl-Phe; R 6 is 4-NH 2 -D-Phe or D-Arg; R 7 is Leu or NαMe-Leu; and R 10 is Gly-NH 2 , NHCH 2 CH 3 or D-Ala-NH 2 .
Claim 3
Dependent Claim
14 words
A peptide in accordance with claim 1 wherein R 2 is 4-Cl-D-Phe or 4-F-D-Phe.
Claim 4
Dependent Claim
12 words
A peptide in accordance with claim 2 wherein R 7 is Leu.
Claim 5
Dependent Claim
12 words
A peptide in accordance with claim 3 wherein R 6 is D-Arg.
Claim 6
Dependent Claim
12 words
A peptide in accordance with claim 4 wherein R 5 is Tyr.
Claim 7
Dependent Claim
11 words
A peptide in accordance with claim 5 wherein X is Ac.
Claim 8
Dependent Claim
11 words
A peptide in accordance with claim 5 wherein X is Acr.
Claim 9
Dependent Claim
16 words
A peptide in accordance with claim 1 wherein X is Ac and R 6 is D-Arg.
Claim 10
Dependent Claim
12 words
A peptide in accordance with claim 8 wherein R 2 is 4-Cl-D-Phe.
Claim 11
Dependent Claim
12 words
A peptide in accordance with claim 8 wherein R 2 is 4-F-D-Phe.
Claim 12
Dependent Claim
36 words
A pharmaceutical composition, comprising as an active ingredient an effective amount of a peptide as defined in claim 1 for regulating the secretion of gonadatropins, in association with a major amount of a nontoxic pharmaceutically-acceptable diluent.
Claim 13
Independent Claim
90 words
A method for regulating the secretion of gonadotropins in mammals, which method comprises administering an effective amount of a peptide having the formula: X-β-D-2NAL-R.sub.2 -D-Trp-Ser-R.sub.5 -R.sub.6 -R.sub.7 -Arg-Pro-R.sub.10 wherein X is hydrogen or an acyl group having 7 or less carbon atoms; R 2 is Cl-D-Phe, F-D-Phe, NO 2 -D-Phe, Cl 2 -D-Phe or Br-D-Phe; R 5 is Tyr or 2-Cl-Phe; R 6 is 4-NH 2 -D-Phe or D-Arg; R 7 is Leu or NαMe-Leu; and R 10 is Gly-NH 2 , NHCH 2 CH 3 or D-Ala-NH 2 .
Claim 14
Independent Claim
90 words
A method for regulating the secretion of gonadotropins in mammals, which method comprises administering an effective amount of a peptide having the formula: X-β-D-2NAL-R.sub.2 -D-Trp-Ser-R.sub.5 -R.sub.6 -R.sub.7 -Arg-Pro-R.sub.10 wherein X is hydrogen or an acyl group having 7 or less carbon atoms; R 2 is Cl-D-Phe, F-D-Phe, NO 2 -D-Phe, Cl 2 -D-Phe or Br-D-Phe; R 5 is Tyr or 2-Cl-Phe; R 6 is 4-NH 2 -D-Phe or D-Arg; R 7 is Leu or NαMe-Leu; and R 10 is Gly-NH 2 , NHCH 2 CH 3 or D-Ala-NH 2 .
Claim 15
Dependent Claim
31 words
A method in accordance with claim 12 wherein said peptide is administered so as to provide a dose in the range of between about 0.1 and 2.5 mg/kg of body weight.
Claim 16
Dependent Claim
57 words
A peptide or a nontoxic salt thereof, said peptide having the formula: X-β-D-2NAL-R.sub.2 -D-Trp-Ser-R.sub.5 -D-Arg-R.sub.7 -Arg-Pro-R.sub.10 wherein X is hydrogen or Ac or Acr; R 2 is 4Cl-D-Phe or 4F-D-Phe; R 5 is Tyr or 2-Cl-Phe; R 7 is Leu or NαMe-Leu; and R 10 is Gly-NH 2 , NHCH 2 CH 3 or D-ala-NH 2 .
Claim 17
Dependent Claim
57 words
A peptide or a nontoxic salt thereof, said peptide having the formula: X-β-D-2NAL-R.sub.2 -D-Trp-Ser-R.sub.5 -D-Arg-R.sub.7 -Arg-Pro-R.sub.10 wherein X is hydrogen or Ac or Acr; R 2 is 4Cl-D-Phe or 4F-D-Phe; R 5 is Tyr or 2-Cl-Phe; R 7 is Leu or NαMe-Leu; and R 10 is Gly-NH 2 , NHCH 2 CH 3 or D-ala-NH 2 .
Claim 18
Dependent Claim
19 words
A peptide in accordance with claim 14 wherein R 5 is 2-Cl-Phe and R 10 is Gly-NH 2 .
Claim 19
Dependent Claim
20 words
A peptide in accordance with claim 15 wherein X is Ac, R 2 is 4F-D-Phe and R 7 is Leu.
Claim 20
Dependent Claim
17 words
A peptide in accordance with claim 14 wherein R 2 is 4F-D-Phe and R 5 is Tyr.
Claim 21
Dependent Claim
18 words
A peptide in accordance with claim 17 wherein X is Ac and R 10 is Gly-NH 2 .
Claim 22
Dependent Claim
17 words
A peptide in accordance with claim 14 wherein R 2 is 4Cl-D-Phe and R 5 is Tyr.
Claim 23
Dependent Claim
24 words
A peptide in accordance with claim 19 wherein X is Ac, R 7 is Leu and R 10 is NHCH 2 CH 3 .
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-04-24 | 1987-10-24 | 1988-04-24 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-04-24 | 1991-10-24 | 1992-04-24 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-04-24 | 1995-10-24 | 1996-04-24 | $7700.00 | Window Closed / Lapsed |