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: 4864019Abstract: A 32,000-Dalton protein with inhibin activity is isolated from porcine follicular fluid which is composed of two chains having molecular weights of about 18,000 and about 14,000 Daltons, which are bound together by disulfide bonding. Microsequencing revealed the NH.sub.2 -terminal portion of the 18 kD chain to be Ser-Thr-Ala-Pro-Leu-Pro-Trp-Pro-Trp-Ser-Pro-Ala-Ala-Leu-Arg-Leu-Leu-Gln-Ar g- Pro-Pro-Glu-Glu-Pro-Ala-Val and of the 14 kD chain to be Gly-Leu-Glu-Cys with the next 21 residues believed to be Asp-Gly-Ser-His-Asn-Leu-Asp-Ser-Arg-Gln-Gln-Phe-Phe-Ile-Asp-Phe-Arg-Leu-Il e-G y-Trp. This 32 kD protein specifically inhibits basal secretion of FSH, but not of LH. Antibodies raised against a synthetic replicate of the N-terminal six residues of the 18 kD chain are effective to reduce the activity of highly purified 32 kD inhibin and may be administered to mammalian animals for the purpose of neutralizing endogenous inhibin and thereby increasing gonadotropin secretion.Type: GrantFiled: August 31, 1987Date of Patent: September 5, 1989Assignee: The Salk Institute for Biological StudiesInventors: Wylie W. Vale, Jean E. F. Rivier, Joachim Spiess
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Patent number: 4843064Abstract: The invention provides peptides which are particularly potent in stimulating the release of pituitary GH in fish and amphibians and which have a substantial portion or all of the following sequence: His-Ala-Asp-Gly-R.sub.5 -Phe-Asn-Lys-Ala-Tyr-Arg-Lys-Ala-Leu-Gly-Gln-Leu- Ser-Ala-Arg-Lys-Tyr-Leu-His-Thr-Leu-R.sub.27 -R.sub.28 -R.sub.29 -R.sub.30 -R.sub.31 -Gly-R.sub.33 -R.sub.34 -R.sub.35 -R.sub.36 -R.sub.37 - R.sub.38 -R.sub.39 -R.sub.40 -R.sub.41 -R.sub.42 -R.sub.43 -R.sub.44 -Ser wherein R.sub.5 is Met, Leu, Val, Nva, Gln, Thr, Ile or Nle; R.sub.27 is Met, Leu, Val, Nva, Gln, Thr, Ile or Nle; R.sub.28 is Ala, Ser or Asn; R.sub.29 is Lys or Arg; R.sub.30 is Arg or Gln; R.sub.31 is Val or Gln; R.sub.33 is Gly or Glu; R.sub.34 is Gly, Arg or Ser; R.sub.35 is Ser or Asn; R.sub.36 is Met, Leu, Val, Nva, Gln, Thr, Ile or Nle; R.sub.37 is Ile or Glu; R.sub.38 is Glu, Gln or Arg; R.sub.39 is Asp, Arg or Gly; R.sub.40 is Asp, Ser or Ala; R.sub.41 is Asn, Arg or Lys; R.sub.42 is Glu, Phe, Ala or Val; R.sub.Type: GrantFiled: September 11, 1987Date of Patent: June 27, 1989Assignee: The Salk Institute for Biological StudiesInventors: Joan Vaughan, Joachim Spiess, Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4784987Abstract: The invention provides peptides which are potent in stimulating the release of pituitary GH in fish and amphibians which have a substantial portion or all of the following sequence: R.sub.1 -R.sub.2 -R.sub.3 -R.sub.4 -R.sub.5 -Phe-R.sub.7 -R.sub.8 -R.sub.9 -Tyr-Arg-R.sub.12 -R.sub.13 -Leu-R.sub.15 -Gln-Leu-R.sub.18 -Ala-Arg-Lys-R.sub.22 -Leu-R.sub.24 -R.sub.25 -R.sub.26 -R.sub.27 -R.sub.28 -R.sub.29 -R.sub.30 -R.sub.31 -Gly-R.sub.33 -R.sub.34 -R.sub.35 -R.sub.36 -R.sub.37 -R.sub.38 -R.sub.39 -R.sub.40 -R.sub.41 -R.sub.42 -R.sub.43 -R.sub.44 -Ser wherein R.sub.1 is N-Me Tyr, Tyr, desNH.sub.2 -Tyr, D-Tyr, N-Et Tyr, N-Ip Tyr, N-Me His, His, desNH.sub.2 -His, D-His, N-Et His, and N-Ip His; R.sub.2 is Ala, D-Ala or D-NMA; R.sub.3 is Asp or D-Asp; R.sub.4 is Gly or Ala; R.sub.5 and R.sub.27 are selected from the group consisting of Met, Leu, Val, Nva, Gln, Thr, Ile, Ala, Arg, Asn, Asp, Cys, Glu, Gly, His, Nle, Lys, Phe, Pro, Ser, Tyr and Trp; R.sub.7 is Asn or Thr; R.sub.8 is Lys, Asn or Ser; R.sub.Type: GrantFiled: June 10, 1987Date of Patent: November 15, 1988Assignee: The Salk Institute for Biological StudiesInventors: Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4740500Abstract: 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: Ac-.beta.-D-NAL-R.sub.2 -D-3PAL-Ser-Arg-R.sub.6 -Leu-Arg-Pro-R.sub.10 wherein R.sub.2 is Cl-D-Phe, F-D-Phe, NO.sub.2 -D-Phe, Br-D-Phe, 3,4Cl.sub.2 -D-Phe or C.alpha.Me-Cl-D-Phe; R.sub.6 is D-3PAL, D-Trp, For-D-Trp, NO.sub.2 -D-Trp, (imBzl)D-His, D-Tyr or .beta.-D-NAL; and R.sub.10 is Gly-NH.sub.2, NHCH.sub.2 CH.sub.3, NHNHCONH.sub.2 or D-Ala-NH.sub.2.Type: GrantFiled: December 23, 1986Date of Patent: April 26, 1988Assignee: The Salk Institute for Biological StudiesInventors: Wylie W. Vale, Jr., Jean E. F. Rivier
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Patent number: 4737578Abstract: Proteins with inhibin activity having a weight of about 32,000 daltons. The molecule is composed of two chains having molecular weights of about 18,000 and about 14,000 daltons, respectively, which are bound together by disulfide bonding. The 18K chain is obtained from the human inhibin gene and has the formula: H-Ser-Thr-Pro-Leu-Met-Ser-Trp-Pro-Trp-Ser-Pro-Ser-Ala-Leu-Arg-Leu-Leu-Gln- Arg-Pro-Pro-Glu-Glu-Pro-Ala-Ala-His-Ala-Asn-Cys-His-Arg-Val-Ala-Leu-Asn-Ile -Ser-Phe-Gln-Glu-Leu-Gly-Trp-Glu-Arg-Trp-Ile-Val-Tyr-Pro-Pro-Ser-Phe-R.sub. 65 -Phe-His-Tyr-Cys-His-Gly-Gly-Cys-Gly-Leu-His-Ile-Pro-Pro-Asn-Leu-Ser-Leu-P ro-Val-Pro-Gly-Ala-Pro-Pro-Thr-Pro-Ala-Gln-Pro-Tyr-Ser-Leu-Leu-Pro-Gly-Ala- Gln-Pro-Cys-Cys-Ala-Ala-Leu-Pro-Gly-Thr-Met-Arg-Pro-Leu-His-Val-Arg-Thr-Thr -Ser-Asp-Gly-Gly-Tyr-Ser-P e-Lys-Tyr-Glu-Thr-Val-Pro-Asn-Leu-Leu-Thr-Gln-His-Cys-Ala-Cys-Ile-OH, wherein R.sub.65 is Ile or Arg. The 18K chain is connected by disulfide bonding to the 14K chain.Type: GrantFiled: April 7, 1986Date of Patent: April 12, 1988Assignee: The Salk Institute for Biological StudiesInventors: Ronald M. Evans, Michael G. Rosenfeld, Gail Cerelli, Kelly E. Mayo, Joachim Spiess, Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4728726Abstract: Human GRF(hGRF), rat GRF(rGRF), porcine GRF(pGRF), ovine GRF(oGRF) 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 contain 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 -R.sub.30 -R.sub.31 -R.sub.32, wherein R.sub.1 is Tyr, D-Tyr, Met, Phe, D-Phe, pCl-Phe, Leu, His or D-His having either a C.sup.a Me or N.sup.a 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.14 is Leu or D-Leu, R.sub.15 is Gly or D-Ala; R.sub.17 is Leu or D-Leu; R.sub.Type: GrantFiled: December 8, 1986Date of Patent: March 1, 1988Assignee: The Salk Institute for Biological StudiesInventors: Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4703035Abstract: Surprisingly active fragments of human pancreatic GRF have been synthesized which exhibit good biological activity. These synthetic peptides are extremely potent in stimulating the release of pituitary GH in humans and in nonhuman animals and have the general formula: H-Tyr-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-Met-Ser-Arg-Y wherein Y is NH.sub.2, Gln-NH.sub.2, Gln-Gln-NH.sub.2 or Gln-Gln-Gly-NH.sub.2. Two such fragments have been tested, namely the 29 and the 32 N-terminal residue sequences that are amidated at the C-terminus. These peptides, as well as nontoxic salts thereof, may be administered therapeutically to animals, including humans.Type: GrantFiled: October 2, 1985Date of Patent: October 27, 1987Assignee: The Salk Institute for Biological StudiesInventors: Jean E. F. Rivier, Joachim Spiess, Wylie W. Vale, Jr.
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Patent number: 4689396Abstract: 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, which can be used for therapeutic treatment. The peptides have the structure:X-R.sub.1 -R.sub.2 -R.sub.3 -Ser-Arg-R.sub.6 -R.sub.7 -Arg-Pro-R.sub.10 wherein X is hydrogen, Acr or Ac; R.sub.1 is .beta.-D-2NAL, dehydroPro or 4Cl-D-Phe; R.sub.2 is Cl-D-Phe, F-D-Phe, NO.sub.2 -D-Phe, Br-D-Phe or C.sup.a Me/Cl-D-Phe; R.sub.3 is D-Trp or .beta.-D-2NAL; R.sub.6 is D-Tyr, .beta.-D-2NAL or D-Arg; R.sub.7 is Leu or NML; and R.sub.10 is Gly-NH.sub.2, NHCH.sub.2 CH.sub.3 or D-Ala-NH.sub.2 ; provided however that R.sub.1 or R.sub.3 or both are .beta.-D-2NAL.Type: GrantFiled: August 30, 1985Date of Patent: August 25, 1987Assignee: The Salk Institute for Biological StudiesInventors: Roger W. Roeske, Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4677193Abstract: GnRH peptide analogs which regulate the secretion of gonadotropins by the pituitary gland and either promote or inhibit the release of steroids by the gonads. Administration of an effective amount of a GnRH antagonist prevents ovulation of female mammalian eggs and/or the release of gonadotropins. Administration of GnRH agonists can be used to regulate fertility in male and female mammals.These and other peptide hormones exhibit improved binding efficiency and biological potency as a result having a residue in a critical, generally central location in the chain which residue contains a mixed alkyl ketone side-chain terminating in an aromatic group. Methods for efficiently synthesizing these peptides from readily available compounds are disclosed.Type: GrantFiled: February 22, 1985Date of Patent: June 30, 1987Assignee: The Salk Institute for Biological StudiesInventors: Jean E. F. Rivier, Harry A. Anderson, Wylie W. Vale, Jr.
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Patent number: 4661472Abstract: 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 of such GnRH antagonists prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads. These peptides may be used to treat steroid-dependent tumors, such as prostatic and mammary tumors. The peptides are cyclic analogs of the decapeptide GnRH wherein there is a covalent bond between the residue in the 4-position and the residue in the 10-position. Examples of such bonds include the disulfide linkage between Cys residues, an amide linkage between a side chain amino group and a side chain carboxyl group, a dicarba linkage between side-chain alkyl groups, and a carba linkage between a side-chain alkyl group and a side-chain sulfhydryl group.Type: GrantFiled: May 9, 1985Date of Patent: April 28, 1987Assignee: The Salk Institute for Biological StudiesInventors: Jean E. F. Rivier, Janos I. Varga, Arnold T. Hagler, R. Scott Struthers, Marilyn H. Perrin, Catherine L. Rivier, Wylie W. Vale, Jr.
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Patent number: 4652550Abstract: 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.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.1 is dehydro-Pro or .beta.-D-NAL; R.sub.2 is Cl-D-Phe, F-D-Phe, NO.sub.2 -D-Phe, C.sup..alpha. Me-4-Cl-D-Phe, Cl.sub.2 -D-Phe or Br-D-Phe; R.sub.3 is D-Trp, substituted D-Trp, .beta.-D-NAL, or D-PAL; R.sub.6 is a D-isomer of a lipophilic amino acid or is 4-NH.sub.2 -D-Phe, D-Lys, D-Orn, D-Har, D-His, 4-gua-D-Phe, D-PAL or D-Arg; R.sub.7 is Nle, Phe, Met, Tyr, Nva, Trp, Cys, PAL or 4F-D-Phe; and R.sub.10 is Gly-NH.sub.2 or D-Ala-NH.sub.2 ; provided however that when R.sub.1 is .beta.-D-NAL, then R.sub.6 is 4-NH.sub.2 -D-Phe, D-Lys, D-Orn, D-Har, D-His, 4-gua-D-Phe, D-PAL or D-Arg.Type: GrantFiled: September 21, 1984Date of Patent: March 24, 1987Assignee: The Salk Institute for Biological StudiesInventors: Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4628043Abstract: Synthetic peptides are provided which are extremely potent in stimulating the release of pituitary GH in animals and which have the formula: H--R.sub.1 --Ala--Asp--Ala--Ile--Phe--Thr--R.sub.8 --Ser--R.sub.10 --Arg--R.sub.12 --R.sub.13 --Leu--R.sub.15 --Gln--Leu--R.sub.18 --Ala--Arg--Lys--Leu--Leu--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 --Leu--Y wherein R.sub.1 is Tyr, Met, Leu, D--Tyr, D--His or His; R.sub.8 is Ser or 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.15 is Gly or D--Ala; R.sub.18 is Tyr or Ser; R.sub.24 is His or Gln; R.sub.25 is Glu or Asp; R.sub.27 is Met, Ala, Nle, Ile, Leu or Val; R.sub.28 is Asn or Ser; R.sub.34 is Arg or Ser; R.sub.38 is Gln or Arg; R.sub.39 is Arg or Gly; R.sub.40 is Ser or Ala; R.sub.42 is Phe or Ala; R.sub.Type: GrantFiled: March 21, 1985Date of Patent: December 9, 1986Assignee: The Salk Institute for Biological StudiesInventors: Joachim Spiess, Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4626523Abstract: Human pancreatic GRF(hpGRF) and rat hypothalamic GRF(rhGRF) 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 are resistant to enzymatic degradation in the body, and which have the sequence: R.sub.1 -Ala-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-Leu-R.sub.18 -Ala-Arg-Lys-Leu-Leu-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 -Y wherein R.sub.1 is Tyr, D-Tyr, Met, Phe, D-Phe, pCl-Phe, Leu, His or D-His having either a C.sup.a Me or N.sup.a Me substitution; 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.15 is Gly or D-Ala; R.sub.18 is Tyr or Ser; R.sub.24 is His or Gln; R.sub.25 is Glu or Asp; R.sub.Type: GrantFiled: June 10, 1985Date of Patent: December 2, 1986Assignee: The Salk Institute for Biological StudiesInventors: Wylie W. Vale, Jr., Jean E. F. Rivier
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Patent number: 4619914Abstract: 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 -D-Trp-Ser-R.sub.5 -R.sub.6 -Leu-Arg-Pro-R.sub.10wherein X is hydrogen or an acyl group having 7 or less carbon atoms; R.sub.1 is dehydro-Pro, D-pGlu, D-Phe, D-Trp or .beta.-D-NAL; R.sub.2 is Cl-D-Phe, F-D-Phe, C.sup..alpha. Me-4-Cl-D-Phe, NO.sub.2 -D-Phe, Cl.sub.2 -D-Phe or Br-D-Phe; R.sub.5 is Tyr, I-Tyr, CH.sub.3 -Phe, F-Phe or Cl-Phe; R.sub.6 is a D-isomer of a lipophilic amino acid or is 4-NH.sub.2 -D-Phe, 4-gua-D-Phe, D-His, D-Lys, D-Orn, D-Har or D-Arg; and R.sub.10 is Gly-NH.sub.2, D-Ala-NH.sub.2 or NH-Y, with Y being lower alkyl, cycloalkyl, fluoro lower alkyl or ##STR1## where Q is H or lower alkyl. When R.sub.1 is .beta.-D-NAL, R.sub.6 is 4-NH.sub.Type: GrantFiled: February 23, 1984Date of Patent: October 28, 1986Assignee: The Salk Institute for Biological StudiesInventors: Wylie W. Vale, Jr., Jean E. F. Rivier
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Patent number: 4605642Abstract: Several polypeptide analogs of the known members of the corticotropin releasing factor (CRF) family have been synthesized and tested including human and rat CRF which 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. Peptides are herein disclosed that are potent competitive antagonists of CRF in mammals. One which has been found to be particularly potent is: H-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Met-Leu-Glu-Met-Ala-Lys-Ala-Glu- Gln-Glu-Ala-Glu-Gln-Ala-Ala-Leu-Asn-Arg-Leu-Leu-Leu-Glu-Glu-Ala-NH.sub.2. These antagonists or pharmaceutically or veterinarily acceptable salts thereof, dispersed in a pharmaceutically or veterinarily acceptable liquid or solid carrier, can be administered to mammals, including humans, to achieve a prevent elevation of ACTH, .beta.-endorphin, .beta.Type: GrantFiled: February 23, 1984Date of Patent: August 12, 1986Assignee: The Salk Institute for Biological StudiesInventors: Catherine L. Rivier, Jean E. F. Rivier, Wylie W. Vale, Jr., Marvin R. Brown
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Patent number: 4595676Abstract: Rat hypothalamic GRF has been synthesized and has the formula: H-His-Ala-Asp-Ala-Ile-Phe-Thr-Ser-Ser-Tyr-Arg-Arg-Ile-Leu-Gly-Gln-Leu-Tyr- Ala-Arg-Lys-Leu-Leu-His-Glu-Ile-Met-Asn-Arg-Gln-Gln-Gly-Glu-Arg-Asn-Gln-Glu -Gln-Arg-Ser-Arg-Phe-Asn-OH. The peptide is believed to be and is hereinafter referred to as rhGRF (for rat hypothalamic GH releasing factor). The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in animals and which have the formula: H-R.sub.1 -Ala-Asp-Ala-Ile-Phe-Thr-R.sub.8 -Ser-R.sub.10 -Arg-R.sub.12 -R.sub.13 -Leu-R.sub.15 -Gln-Leu-R.sub.18 -Ala-Arg-Lys-Leu-Leu-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 -Y wherein R.sub.1 is Tyr, Met, D-Tyr, Leu, D-His or His; R.sub.8 is Ser or 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.15 is Gly or D-Ala; R.sub.18 is Tyr or Ser; R.sub.24 is His or Gln; R.Type: GrantFiled: April 26, 1983Date of Patent: June 17, 1986Assignee: The Salk Institute for Biological StudiesInventors: Joachim Spiess, Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4594329Abstract: Analogs of rCRF and oCRF are disclosed that can be administered 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. One analog which has been found to be particularly potent is: H-Ser-Gln-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Met- Leu-Glu-Met-Ala-Lys-Ala-Glu-Gln-Glu-Ala-Glu-Gln-Ala-Ala-Leu-Asn-Arg-Leu-Leu -Leu-Glu-Glu-Ala-NH.sub.2. In the analogs, one or more of the first five 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. A number of other substitutions may also be made throughout the chain. These analogs or pharmaceutically or veterinarily acceptable salts thereof, dispersed in a pharmaceutically or veterinarily acceptable liquid or solid carrier, can be administered to mammals, including humans.Type: GrantFiled: May 14, 1984Date of Patent: June 10, 1986Assignee: The Salk Institute for Biological StudiesInventors: Wylie W. Vale, Jr., Jean E. F. Rivier
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Patent number: 4569927Abstract: 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 -(W)D-Phe-R.sub.3 -R.sub.4 -R.sub.5 -R.sub.6 -R.sub.7 -Arg-Pro-R.sub.10wherein X is hydrogen or an acyl group having 7 or less carbon atoms; R.sub.1 is dehydro-Pro, D-pGlu, D-Phe, D-Trp of .beta.-D-NAL; W is F, Cl, Cl.sub.2 Br, NO.sub.2 or C.sup..alpha. Me-Cl; R.sub.3 is (N.sup.in For)D-Trp or D-Trp which is substituted in the 5- or 6-position with NO.sub.2, NH.sub.2, OCH.sub.3, F, Cl, Br or CH.sub.3 ; R.sub.4 is Ser, Orn, AAL or aBu; R.sub.5 is Tyr, Arg, (3F)Phe, (2F)Phe, (3I)Tyr, (3CH.sub.3)Phe, (2CH.sub.3)Phe, (3Cl)Phe or (2Cl)Phe; R.sub.6 is (4NH.sub.2)D-Phe, D-Lys, D-Orn, D-Har, D-His, (4gua)D-Phe, D-Tyr, a D-isomer of a lipophilic amino or D-Arg; R.sub.7 is Leu, NML, Nle or Nva; and R.sub.10 is Gly-NH.sub.Type: GrantFiled: May 21, 1984Date of Patent: February 11, 1986Assignee: The Salk Institute For Biological StudiesInventors: Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4565804Abstract: 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 -(W)D-Phe-R.sub.3 -R.sub.4 -R.sub.5 -R.sub.6 (V)-R.sub.7 -Arg-Pro-R.sub.10 wherein X is hydrogen or an acyl group having 7 or less carbon atoms; R.sub.1 is dehydro-Pro, Pro, D-pGlu, D-Phe, D-Trp or .beta.-D-NAL; W is F, Cl, Cl.sub.2 Br, NO.sub.2 or C.sup..alpha. Me-Cl; R.sub.3 is D-Trp, (N.sup.in For)D-Trp or D-Trp which is substituted in the 5- or 6-position with NO.sub.2, NH.sub.2, OCH.sub.3, F, Cl, Br or CH.sub.3 ; R.sub.4 is Ser, Orn, AAL or aBu; R.sub.5 is Tyr, (3F)Phe, (2F)Phe, (3I)Tyr, (3CH.sub.3)Phe, (2CH.sub.3)Phe, (3Cl)Phe or (2Cl)Phe; R.sub.6 is D-Lys, D-Orn or D-Dap; V is (arg-R',R").sub.n (X), with n being 1 to 5 and R' and R" being H, methyl, ethyl, propyl or butyl; R.sub.Type: GrantFiled: September 7, 1984Date of Patent: January 21, 1986Assignee: The Salk Institute For Biological StudiesInventors: Jean E. F. Rivier, Wylie W. Vale, Jr.
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Patent number: 4563352Abstract: Human pancreatic GRF has been synthesized. The invention provides synthetic peptides which are extremely potent in stimulating the release of pituitary GH in mammals and which have the formula: H-Tyr-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-Met-Ser-Arg-Gln-Gln-Gly-Glu-S er-Asn-Gln-Glu-Arg-Gly-R.sub.40 -R.sub.41 -R.sub.42 -Y wherein R.sub.15 is Gly or D-Ala, R.sub.40 is Ala or des-R.sub.40, R.sub.41 is Phe or des-R.sub.41, R.sub.42 is des-R.sub.42 or 1 to 8 different amino acid residues selected from the group consisting of Gln, Gly, Ile, Leu, Lys, Pro, Thr 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.Type: GrantFiled: October 4, 1982Date of Patent: January 7, 1986Assignee: The Salk Institute For Biological StudiesInventors: Jean E. F. Rivier, Joachim Spiess, Wylie W. Vale, Jr.