Patents by Inventor Wylie W. Vale
Wylie W. Vale has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 4530838Abstract: CGRP (calcitonin-gene-related peptide) has the formula: ##STR1## A related peptide has the residue Lys instead of Glu in the 35-position. CGRP or this homolog or pharmaceutically acceptable salts thereof, dispersed in a pharmaceutically acceptable liquid or solid carrier, can be administered to mammals, including humans, to influence memory, mood and pain appreciation and to achieve a substantial lowering of blood pressure or gastric acid secretion over an extended period of time. They also may be administered to affect ingestion behavior, taste and sensory perception.Type: GrantFiled: July 8, 1983Date of Patent: July 23, 1985Assignee: The Salk Institute for Biological StudiesInventors: Ronald M. Evans, Larry Swanson, Wylie W. Vale, Jr., Michael G. Rosenfeld, Susan G. Amara, Marvin R. Brown, Jean E. F. Rivier
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Patent number: 4529595Abstract: 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.sub.15 -Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-R.sub.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.sub.15 is Gly or D-Ala, R.sub.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.sub.1,--CR.sub.1 O,--CONHNHR.sub.1,--CON(R.sub.1)(R.sub.2) or --CH.sub.2 OR.sub.1, with R.sub.1 and R.sub.2 being lower alkyl or hydrogen, provided that when R is Tyr, R.sub.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.Type: GrantFiled: January 13, 1983Date of Patent: July 16, 1985Assignee: The Salk Institute for Biological StudiesInventors: Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4528190Abstract: Human GRF(hGRF), rat GRF(rGRF) porcine GRF(pGRF) and bovine GRF(bGRF) have been earlier characterized and synthesized. The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in animals, including humans, which have resistance to enzymatic degradation in the body, and which have the sequence: R.sub.1 -R.sub.2 -R.sub.3 -Ala-Ile-Phe-Thr-R.sub.8 -Ser-R.sub.10 -Arg-R.sub.12 -R.sub.13 -R.sub.14 -R.sub.15 -Gln-R.sub.17 -R.sub.18 -Ala-Arg-Lys-Leu-R.sub.23 -R.sub.24 -R.sub.25 -Ile-R.sub.27 -R.sub.28 -R.sub.29 -Gln-Gln-Gly-Glu-R.sub.34 -Asn-Gln-Glu-R.sub.38 -R.sub.39 -R.sub.40 -Arg-R.sub.42 -R.sub.43 -R.sub.44 wherein R.sub.1 is Tyr, D-Tyr, Met, Phe, D-Phe, pCl-Phe, Leu, His or D-His having either a C.sup..alpha. Me or N.sup..alpha. Me substitution or being unsubstituted; R.sub.2 is Ala, D-Ala or D-NMA; R.sub.3 is Asp or D-Asp; R.sub.8 is Ser, Asn, D-Ser or D-Asn; R.sub.10 is Tyr or D-Tyr; R.sub.12 is Arg or Lys; R.sub.13 is Ile or Val; R.sub.Type: GrantFiled: May 18, 1984Date of Patent: July 9, 1985Assignee: The Salk Institute For Biological StudiesInventors: Wylie W. Vale, Jr., Jean E. F. Rivier
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Patent number: 4518586Abstract: Human parcreatic GRF(hpGRF), rat hypothalamic GRF(rGRF) and porcine hypothalamic GRF(pGRF) have been earlier characterized and synthesized. The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in animals, including humans, which have resistance to enzymatic degradation in the body, and which have the sequence: R.sub.1 -R.sub.2 -R.sub.3 -Ala-Ile-Phe-Thr-R.sub.8 -Ser-R.sub.10 -Arg-R.sub.12 -R.sub.13 -Leu-R.sub.15 -Gln-R.sub.17 -R.sub.18 -Ala-Arg-Lys-Leu-R.sub.23 -R.sub.24 -R.sub.25 -Ile-R.sub.27 -R.sub.28 -Arg-Gln-Gln-Gly-Glu-R.sub.34 -Asn-Gln-Glu-R.sub.38 -R.sub.39 -R.sub.40 -Arg-R.sub.42 -R.sub.43 -R.sub.44 wherein R.sub.1 is Tyr, D-Tyr, Met, Phe, D-Phe, pCl-Phe, Leu, His or D-His having either a C.sup..alpha. Me or N.sup..alpha. Me substitution or being unsubstituted; R.sub.2 is Ala or D-Ala; R.sub.3 is Asp or D-Asp; R.sub.8 is Ser, Asn, D-Ser or D-Asn; R.sub.10 is Tyr or D-Tyr; R.sub.12 is Arg or Lys; R.sub.13 is Ile or Val; R.sub.Type: GrantFiled: October 25, 1983Date of Patent: May 21, 1985Assignee: The Salk Institute for Biological StudiesInventors: Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4489061Abstract: Peptides which are LRF analogs that inhibit the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads can be effective to suppress androgen-dependent behavior when administered to male mammals. The peptides are LRF antagonists having a binding affinity at least about 15 times that exhibited by LRF and having an ICR.sub.50 of less than 1/1. Examples of peptides which may be used are those having the structure:R.sub.1 -R.sub.2 -R.sub.3 -D-Trp-Ser-Tyr-R.sub.4 -Leu-Arg-Pro-Gly-NH.sub.2 wherein R.sub.1 is selected from the group consisting of hydrogen, formyl, acetyl, acrylyl, benzoyl and allyl; R.sub.2 is selected from the group consisting of dehydro Pro, dehydro D-Pro, Thz and D-Thz; R.sub.3 is selected from the group consisting of pCl-D-Phe, pF-D-Phe, pNO.sub.2 -D-Phe and 3,4 Cl-D-Phe; R.sub.4 is selected from the group consisting of D-Trp and (imBzl) D-His; and Leu may be substituted by N.alpha.MeLeu.Type: GrantFiled: September 27, 1982Date of Patent: December 18, 1984Assignee: The Salk Institute for Biological StudiesInventors: Catherine L. Rivier, Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4489163Abstract: rCRF (rat Corticotropin Releasing Factor) has been isolated, characterized and found to have the formula: H-Ser-Glu-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val- Leu-Glu-Met-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu -Met-Glu-Ile-Ile-NH.sub.2. Analogs are disclosed that are at least as potent as rCRF, and rCRF or these analogs orpharmaceutically or veterinarily acceptable salts thereof, dispersed in a pharmaceutically or veterinarily acceptable liquid or solid carrier, can be administered to animals, including humans, to achieve a substantial elevation of ACTH, .beta.-endorphin, .beta.-lipotropin, other products of the pro-opiomelanocortin gene and corticosterone levels and/or a lowering of blood pressure over an extended period of time. They may also be used as stimulants to elevate mood and improve memory and learning, as well as diagnostically.Type: GrantFiled: April 14, 1983Date of Patent: December 18, 1984Assignee: The Salk Institute for Biological StudiesInventors: Jean E. F. Rivier, Joachim Spiess, Wylie W. Vale, Jr.
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Patent number: 4444759Abstract: 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-.beta.-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.sub.2 is Cl-D-Phe, F-D-Phe, NO.sub.2 -D-Phe, Cl.sub.2 -D-Phe or Br-D-Phe; R.sub.5 is Tyr or Cl-Phe; R.sub.6 is 4-NH.sub.2 -D-Phe or D-Arg; R.sub.7 is Leu or N.alpha.Me-Leu; and R.sub.10 is Gly-NH.sub.2, NHCH.sub.2 CH.sub.3 or D-Ala-NH.sub.2.Type: GrantFiled: July 26, 1982Date of Patent: April 24, 1984Assignee: The Salk Institute for Biological StudiesInventors: Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4443368Abstract: The peptide having the following formula has a potent effect on the reproduction processes of fish and is termed Fish GnRH:pGlu-His-Trp-Ser-Tyr-Gly-Trp-Leu-Pro-Gly-NH.sub.2.Spawning of teleostei fish can be promoted by administration of effective amounts of the peptide.Type: GrantFiled: November 1, 1982Date of Patent: April 17, 1984Assignee: The Salk Institute for Biological StudiesInventors: Nancy M. Sherwood, Lee E. Eiden, Michael J. Brownstein, Joachim Spiess, Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4428942Abstract: Somatostatin-14 has the formula: ##STR1## Analogs that are more potent than somatostatin-14 in increasing electrolyte absorption in the gut without suppressing the secretion of GH, insulin and glucagon, or pharmaceutically acceptable salts thereof, dispersed in a pharmaceutically acceptable liquid or solid carrier, can be administered to mammals in the same manner as somatostatin to increase absorbtion of electrolytes for the treatment of diarrhea. In particular of the analogs, certain substitutions are made for Phe in the 11-position, sometimes in combination with deletions in the 4- and 5-positions and in the 12- and 13-positions. D-Cys may also be substituted in the 3- or 14-position. There may be some substitutions in the 6- and 10-positions, and the residues in the 1- and/or 2-positions may also be deleted or substituted.Type: GrantFiled: May 17, 1982Date of Patent: January 31, 1984Assignee: The Salk Institute for Biological StudiesInventors: Jean E. F. Rivier, Wylie W. Vale, Jr., Marvin R. Brown
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Patent number: 4415558Abstract: CRF (Corticotropin Releasing Factor) has the formula:H-Ser-Gln-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val-L eu-Glu-Met-Thr-Lys-Ala-Asp-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu- Leu-Asp-Ile-Ala-NH.sub.2.Analogs have been synthesized that are at least as potent as CRF, and CRF or these analogs or pharmaceutically acceptable salts thereof, dispersed in a pharmaceutically acceptable liquid or solid carrier, can be administered to mammals to achieve a substantial elevation of ACTH, .beta.-endorphin, .beta.-lipotropin and corticosterone levels and/or a lowering of blood pressure over an extended period of time. In the analogs, one or more of the first three N-terminal residues may be deleted or may be substituted by a peptide up to 10 amino acids long and/or by an acylating agent containing up to 7 carbon atoms. Ala in the 41-position may also be substituted or deleted so long as the remaining C-terminus is amidated. Several other substitutions may also be made throughout the chain.Type: GrantFiled: May 17, 1982Date of Patent: November 15, 1983Assignee: The Salk Institute for Biological StudiesInventors: Wylie W. Vale, Jr., Joachim Spiess, Catherine L. Rivier, Jean E. F. Rivier
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Patent number: 4410514Abstract: Peptides for promoting the spawning of fish having the formula:pGlu--His--Trp--Ser--Tyr--R.sub.6 --Trp--Leu--Pro--R.sub.10 --NHRor a nontoxic salt thereof, wherein R.sub.6 is a D-isomer of an .alpha.-amino acid selected from the group consisting ofTrp, Ala, Phe, Lys, Pro, Met, Leu, Glu, Asn, Arg, Tyr, Cys, His, Chg, Nva, Orn, Thr, Abu, Phg, Ile, Glu, Asp, Nle and Val and wherein R.sub.10 is Gly or des-R.sub.10 and R is H or C.sub.n Y.sub.2n CY.sub.3, with Y being H or F and n being 0, 1, 2 or 3, provided that when R.sub.10 is des-R.sub.10, n is not 0. The D-isomer .alpha.-amino acids may contain known substitutions.Type: GrantFiled: December 6, 1982Date of Patent: October 18, 1983Assignee: The Salk Institute for Biological StudiesInventors: Wylie W. Vale, Jr., Jean E. F. Rivier
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Patent number: 4409208Abstract: 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 gonads. The peptides have the structure.X-R.sub.1 -R.sub.2 -R.sub.3 -Ser-Tyr-R.sub.4 -R.sub.5 -Arg-Pro-R.sub.6wherein X is hydrogen or an acyl group having 7 or less carbon atoms; R.sub.1 is dehydro Pro or dehydro D-Pro; R.sub.2 is D-Phe, Cl-D-Phe, dichloro-D-Phe, CF.sub.3 -D-Phe, F-D-Phe, difluoro-D-Phe, AcNH-D-Phe, NO.sub.2 -D-Phe, dinitro-D-Phe, Br-D-Phe, dibromo-D-Phe, CH.sub.3 -S-D-Phe, OCH.sub.3 -D-Phe or CH.sub.3 -D-Phe; R.sub.3 is D-Trp or .beta.-(naphthyl)-D-Ala; R.sub.4 is a D-isomer aromatic amino acid or .beta.-(naphthyl)-D-Ala; R.sub.5 is Leu or N.alpha.Me-Leu; and R.sub.6 is Gly-NH.sub.2 or NHCH.sub.2 CH.sub.3 ; provided however that either R.sub.3 or R.sub.4 is .beta.-(naphthyl)-D-Ala.Type: GrantFiled: April 21, 1981Date of Patent: October 11, 1983Assignee: The Salk Institute for Biological StudiesInventors: Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4393050Abstract: Somatostatin-28 has the formula: ##STR1## Analogs have been synthesized that are more potent than somatostatin-28, and these analogs or pharmaceutically acceptable salts thereof, dispersed in a pharmaceutically acceptable liquid or solid carrier, can be administered to mammals in the same manner as somatostatin. In the analogs, Leu may be substituted in the 8-position in combination with D-Trp in the 22-position and/or Tyr in the 25-position. D-Cys may also be substituted in the 28-position, and D-Ser may be substituted in the 27-position. Certain residues may also be deleted. D-Trp.sup.22 somatostation-28 has surprisingly been found to be insulin-selective when administered in vivo and is useful for the treatment of insulinoma.Type: GrantFiled: April 29, 1981Date of Patent: July 12, 1983Assignee: The Salk Institute for Biological StudiesInventors: Wylie W. Vale, Jr., Jean E. F. Rivier, Marvin R. Brown
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Patent number: 4386074Abstract: 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 gonads. The peptides have the structure:R.sub.1 -dehydro Pro-R.sub.2 -D-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH.sub.2wherein R.sub.1 is selected from the group consisting of hydrogen, formyl, acetyl, acrylyl, benzoyl and allyl; R.sub.2 is selected from the group consisting dichloro-D-Phe, C.sup..alpha. Me4Cl-D-Phe, (CH.sub.3).sub.5 -D-Phe, CF.sub.3 -D-Phe, F-D-Phe, difluoro-D-Phe, AcNH-D-Phe, NO.sub.2 -D-Phe, dinitro-D-Phe, Br-D-Phe, dibromo-D-Phe, CH.sub.3 S-D-Phe, OCH.sub.3 -D-Phe and CH.sub.3 -D-Phe, wherein any D-isomer amino acid can be substituted for D-Trp in the 6-position, and wherein N.sup..alpha. MeLeu may be substituted for Leu.Type: GrantFiled: July 27, 1981Date of Patent: May 31, 1983Assignee: The Salk Institute for Biological StudiesInventors: Wylie W. Vale, Jr., Jean E. F. Rivier
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Patent number: 4382922Abstract: LRF analogs having a modified D-Phe residue in the 6-position act as superagonists exhibiting potencies many times more than that of LRF. The peptides or their nontoxic salts can be administered by intravenous, subcutaneous, sublingual, oral, intravaginal, intranasal or rectal routes. The peptides can be used to regulate fertility in male and female mammals, including human beings.The peptides are represented by the following formula:p-Glu-His-Trp-Ser-Ty-R.sub.1 -Leu-Arg-Pro-NH-CH.sub.2 -CH.sub.3wherein R.sub.1 is selected from the group consisting of methyl-D-Phe, nitro-D-Phe, and methyoxy-D-Phe.Type: GrantFiled: March 1, 1982Date of Patent: May 10, 1983Assignee: The Salk Institute for Biological StudiesInventors: Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4377574Abstract: Peptides which are LRF analogs that inhibit the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads can be effective contraceptives when administered to male mammals. The peptides are LRF antagonists having a binding affinity at least about 15 times that exhibited by LRF and having an ICR.sub.50 of less than 1/l. Examples of peptides which may be used are those having the structure:R.sub.1 --R.sub.2 --R.sub.3 --D--Trp--Ser--Tyr--R.sub.4 --Leu--Arg--Pro--Gly--NH.sub.2wherein R.sub.1 is selected from the group consisting of hydrogen, formyl, acetyl, acrylyl, benzoyl and allyl; R.sub.2 is selected from the group consisting of dehydro Pro, dehydro D--Pro, Thz and D--Thz; R.sub.3 is selected from the group consisting of pCl--D--Phe, pF--D--Phe, pNO.sub.2 --D--Phe and 3,4 Cl--D--Phe; R.sub.4 is selected from the group consisting of D--Trp and (imBzl) D--His; and Leu may be substituted by N MeLeu.Type: GrantFiled: June 12, 1981Date of Patent: March 22, 1983Assignee: The Salk Institute For Biological StudiesInventors: Catherine L. Rivier, Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4372884Abstract: Various peptides are described which inhibit the secretion of growth hormone by the pituitary gland and inhibit the release of glucagon and insulin by the pancreas.Type: GrantFiled: April 8, 1976Date of Patent: February 8, 1983Assignee: The Salk Institute For Biological StudiesInventors: Marvin R. Brown, Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4307083Abstract: 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 gonads. The peptides have the structure:R.sub.1 -R.sub.2 -R.sub.3 -Ser-Tyr-R.sub.4 -R.sub.5 -Arg-R.sub.6wherein R.sub.1 is selected from the group consisting of dehydro Pro, dehydro D-Pro, Acetyl dehydro Pro and acetyl dehydro D-Pro; R.sub.2 is selected from the group consisting of D-Phe, Phe, N.alpha.Me-Phe, His, D-His, D-Trp, Trp and N.alpha.Me-Leu; R.sub.3 is selected from the group consisting of D-Trp, Trp D-Phe, Phe, Pro and D-His; R.sub.4 is selected from the group consisting of Gly, D-Trp, D-Phe, imBzl-D-His and D-Tyr; R.sub.5 is selected from the group consisting of Leu and N.alpha.Me-Leu; and R.sub.6 is selected from the group consisting of Pro-Gly-NH.sub.2 and Pro-NH-CH.sub.2 -CH.sub.3.Type: GrantFiled: May 8, 1980Date of Patent: December 22, 1981Assignee: The Salk Institute for Biological StudiesInventors: Jean E. F. Rivier, Catherine L. Rivier, Wylie W. Vale, Jr.
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Patent number: 4292313Abstract: 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 gonads. The peptides have the structure:R.sub.1 -R.sub.2 -pCl-D-Phe-D-Trp-Ser-Tyr-R.sub.3 -R.sub.4 -Arg-Pro-R.sub.5wherein R.sub.1 is selected from the group consisting of hydrogen, formyl, acetyl, acrylyl, benzoyl and allyl; R.sub.2 is selected from the group consisting of dehydro Pro, dehydro D-Pro, Thz and D-Thz; R.sub.3 is selected from the group consisting of D-Trp and (imBzl)D-His; R.sub.4 is selected from the group consisting of Leu and N.sup..alpha. MeLeu; and R.sub.5 is selected from the group consisting of Gly-NH.sub.2 and NHCH.sub.2 CH.sub.3.Type: GrantFiled: April 15, 1980Date of Patent: September 29, 1981Assignee: The Salk Institute for Biological StudiesInventors: Wylie W. Vale, Jr., Jean E. F. Rivier
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Patent number: 4261887Abstract: Peptides have been synthesized which influence the secretion of gonadotropins by the pituitary gland of mammalians, including humans. Some of the peptides promote the release of gonadotropins, while other peptides inhibit the release.Type: GrantFiled: November 7, 1977Date of Patent: April 14, 1981Assignee: The Salk Institute for Biological StudiesInventors: Max S. Amoss, Michael W. Monahan, Wylie W. Vale, Jr.