Patent US4529595A successfully refreshed from Google Patents.
US4529595A
Expired / Lapsed
US
⏱️ 0.0 years remaining
GRF Analogs
Assignee: SLK INSTITUTE FOR BIOLOGICAL STUDIES A NOT-FOR PROFIT CORP OF CA
•
Filing: 1983-01-13
•
Granted: 1985-07-16
•
Expires: 2003-01-13
Abstract
Abstract Human pancreatic GRF analogs which are extremely potent in stimulating the release of pituitary GH in mammals and which have the formula: H-R-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-R 15 -Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-R 27 -Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Y wherein R is selected from the D- and L-isomers of Tyr, Phe and His, R 15 is Gly or D-Ala, R 27 is selected from the group consisting of the D- and L-isomers of Ala, Nle, Ile, Leu, Met and Val, and Y signifies the carboxyl moiety of the amino acid residue at the C-terminal and is the radical --COOR 1 ,--CR 1 O,--CONHNHR 1 ,--CON(R 1 )(R 2 ) or --CH 2 OR 1 , with R 1 and R 2 being lower alkyl or hydrogen, provided that when R is Tyr, R 27 is other than Met. Phe may be substituted for Tyr in the 10-position, and D-Ala may be substituted for Gly in the 28-position. These peptides or biologically active fragments thereof, which will generally extend from the N-terminal to the vicinity of a residue between positions 27 and 32, as well as nontoxic salts of any of the foregoing, may be administered therapeutically to animals, including humans, and may be used diagnostically.
Inventors
- 👤 Jean E. F. Rivier
- 👤 Wylie W. Vale, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 20:47
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/575; C07K14/60; A; A23; A23K; A23K20/00; A23K20/10; A23K20/142; A23K20/147; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/12
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
165 words
A synthetic peptide having the formula: H-R-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-R 27 -Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Y wherein R is selected from the D- and L-isomers of Tyr, Phe and His, R 27 is selected from the group consisting of the D- and L-isomers of Ala, Nle, Ile, Leu, Met and Val and Y signifies the carboxyl moiety of the amino acid residue at the C-terminal and is the radical --COOR 1 , --CR 1 O, --CONHNHR 1 , --CON(R 1 )(R 2 ) or --CH 2 OR 1 , with R 1 and R 2 being lower alkyl or hydrogen, wherein D-Ala can be substituted for Gly in the 15-position or for Ser in the 28-position, and wherein Phe can be substituted for Tyr in the 10-position, provided however that when R is Tyr, R 27 is other than Met; or a biologically active fragment thereof extending from R at the N-terminus to a residue in any of positions 27 through 39 as its C-terminus; or a nontoxic salt of the foregoing.
Claim 2
Dependent Claim
165 words
A synthetic peptide having the formula: H-R-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-R 27 -Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Y wherein R is selected from the D- and L-isomers of Tyr, Phe and His, R 27 is selected from the group consisting of the D- and L-isomers of Ala, Nle, Ile, Leu, Met and Val and Y signifies the carboxyl moiety of the amino acid residue at the C-terminal and is the radical --COOR 1 , --CR 1 O, --CONHNHR 1 , --CON(R 1 )(R 2 ) or --CH 2 OR 1 , with R 1 and R 2 being lower alkyl or hydrogen, wherein D-Ala can be substituted for Gly in the 15-position or for Ser in the 28-position, and wherein Phe can be substituted for Tyr in the 10-position, provided however that when R is Tyr, R 27 is other than Met; or a biologically active fragment thereof extending from R at the N-terminus to a residue in any of positions 27 through 39 as its C-terminus; or a nontoxic salt of the foregoing.
Claim 3
Dependent Claim
13 words
A synthetic peptide having the formula of claim 1 wherein R is His.
Claim 4
Dependent Claim
15 words
A synthetic peptide having the formula of claim 2 wherein Y is CONH 2 .
Claim 5
Dependent Claim
14 words
A synthetic peptide having the formula of claim 3 wherein R 27 is Nle.
Claim 6
Dependent Claim
15 words
A synthetic peptide having the formula of claim 4 having only residues 1 through 32.
Claim 7
Dependent Claim
14 words
A synthetic peptide having the formula of claim 1 wherein R 27 is Nle.
Claim 8
Dependent Claim
18 words
A synthetic peptide having the formula of claim 6 wherein D-Ala is substituted for Ser in the 28-position.
Claim 9
Dependent Claim
15 words
A synthetic peptide having the formula of claim 6 having only residues 1 through 32.
Claim 10
Dependent Claim
13 words
A synthetic peptide having the formula of claim 1 wherein R is D-Tyr.
Claim 11
Dependent Claim
14 words
A synthetic peptide having the formula of claim 9 wherein R 27 is Nle.
Claim 12
Dependent Claim
14 words
A synthetic peptide having the formula of claim 1 wherein R 27 is Val.
Claim 13
Dependent Claim
14 words
A synthetic peptide having the formula of claim 1 wherein R 27 is Ile.
Claim 14
Dependent Claim
18 words
A synthetic peptide having the formula of claim 1 wherein Phe is substituted for Tyr in the 10-position.
Claim 15
Dependent Claim
37 words
A composition for stimulating the release of GH in an animal comprising an effective amount of the peptide of claim 1 or a nontoxic salt thereof, and a veterinarily or pharmaceutically acceptable liquid or solid carrier therefor.
Claim 16
Dependent Claim
29 words
A method of stimulating the release of growth hormone in an animal, which comprises administering to said animal an effective amount of a composition as defined in claim 14.
Claim 17
Dependent Claim
20 words
A method in accordance with claim 15 wherein said administering is carried out either orally, intravenously, subcutaneously, intramuscularly or intranasally.
Claim 18
Independent Claim
181 words
A method of stimulating the release of GH in a mammal by administering an effective amount of a compound having the formula: H-R-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-R 27 -Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Y wherein R is selected from the D- and L-isomers of Tyr, Phe and His, R 27 is selected from the group consisting of the D- and L-isomers of Ala, Nle, Ile, Leu, Met and Val and Y signifies the carboxyl moiety of the amino acid residue at the C-terminal and is the radical --COOR 1 , --CR 1 O, --CONHNHR 1 , --CON(R 1 )(R 2 ) or --CH 2 OR 1 , with R 1 and R 2 being lower alkyl or hydrogen, wherein D-Ala can be substituted for Gly in the 15-position or for Ser in the 28-position, and wherein Phe can be substituted for Tyr in the 10-position, provided however that when R is Tyr, R 27 is other than Met; or a biologically active fragment thereof extending from R at the N-terminus to a residue in any of positions 27 through 39 as its C-terminus; or a nontoxic salt of the foregoing.
Claim 19
Independent Claim
181 words
A method of stimulating the release of GH in a mammal by administering an effective amount of a compound having the formula: H-R-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-R 27 -Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Y wherein R is selected from the D- and L-isomers of Tyr, Phe and His, R 27 is selected from the group consisting of the D- and L-isomers of Ala, Nle, Ile, Leu, Met and Val and Y signifies the carboxyl moiety of the amino acid residue at the C-terminal and is the radical --COOR 1 , --CR 1 O, --CONHNHR 1 , --CON(R 1 )(R 2 ) or --CH 2 OR 1 , with R 1 and R 2 being lower alkyl or hydrogen, wherein D-Ala can be substituted for Gly in the 15-position or for Ser in the 28-position, and wherein Phe can be substituted for Tyr in the 10-position, provided however that when R is Tyr, R 27 is other than Met; or a biologically active fragment thereof extending from R at the N-terminus to a residue in any of positions 27 through 39 as its C-terminus; or a nontoxic salt of the foregoing.
Claim 20
Dependent Claim
105 words
A composition for stimulating the release of GH in an animal comprising an effective amount of a peptide or a nontoxic salt thereof having the sequence: R-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-R 10 -Arg-Lys-Val-Leu-R 15 -Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-R 27 ; wherein R is selected from the D- and L-isomers of Tyr, Phe and His, R 10 is Tyr or Phe, R 15 is Gly or D-Ala, and R 27 is selected from the group consisting of the D- and L-isomers of Ala, Nle, Ile, Leu, Met and Val; provided however that when R is Tyr, R 27 is other than Met; and a veterinarily or pharmaceutically acceptable liquid or solid carrier therefor.
Claim 21
Dependent Claim
105 words
A composition for stimulating the release of GH in an animal comprising an effective amount of a peptide or a nontoxic salt thereof having the sequence: R-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-R 10 -Arg-Lys-Val-Leu-R 15 -Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-R 27 ; wherein R is selected from the D- and L-isomers of Tyr, Phe and His, R 10 is Tyr or Phe, R 15 is Gly or D-Ala, and R 27 is selected from the group consisting of the D- and L-isomers of Ala, Nle, Ile, Leu, Met and Val; provided however that when R is Tyr, R 27 is other than Met; and a veterinarily or pharmaceutically acceptable liquid or solid carrier therefor.
Claim 22
Dependent Claim
29 words
A composition for stimulating the release of growth hormone in an animal as defined in claim 18 having the sequence: R-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-R 10 -Arg-Lys-Val-Leu-R 15 -Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-R 27 -R 28 -Arg-Gln-Gln-Gly.
Claim 23
Dependent Claim
12 words
A composition as defined in claim 19 wherein R 27 is Nle.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1988-07-15 | 1989-01-14 | 1989-07-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-07-15 | 1993-01-14 | 1993-07-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-07-15 | 1997-01-14 | 1997-07-16 | $7700.00 | Window Closed / Lapsed |