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).
-
Patent number: 6495343Abstract: In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of ≦10 nM of CRF occupy ≧50% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. Invention CRF-Rs can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.Type: GrantFiled: January 17, 1995Date of Patent: December 17, 2002Assignee: The Salk Institute for Biological StudiesInventors: Marilyn H. Perrin, Ruoping Chen, Kathy A. Lewis, Wylie W. Vale, Jr., Cynthia J. Donaldson, Paul Sawchenko
-
Patent number: 6482608Abstract: In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of 10 nM of CRF occupy 50% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. Invention CRF-Rs can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.Type: GrantFiled: May 26, 2000Date of Patent: November 19, 2002Assignee: The Salk Institute for Biological StudiesInventors: Marilyn H. Perrin, Ruoping Chen, Kathy A. Lewis, Wylie W. Vale, Jr., Cynthia J. Donaldson, Paul Sawchenko
-
Publication number: 20020127221Abstract: A human urocortin-related peptide with significant sequence homology to the CRF neuropeptide family was identified. A mouse cDNA was isolated from whole brain poly (A+) RNA that encodes a predicted 38 amino acid peptide protein designated herein as urocortin II. Both human URP and mouse Ucn II are structurally related to the other known mammalian family members, CRF and urocortin (Ucn). These peptides are involved in the regulation of the hypothalamic-pituitary-adrenal axis under basal and stress conditions, suggesting a similar role for URP and Ucn II. Synthesized Ucn-II and URP peptide binds with higher affinity to CRF-R2 than to CRF-R1 Ucn II and human URP appear to be involved in the regulation of body temperature and appetite and may play a role in other stress related phenomenon. These findings identify Ucn II and human URP as a new members of the CRF family of neuropeptides, which are expressed centrally and bind to CRF-R2.Type: ApplicationFiled: July 31, 2001Publication date: September 12, 2002Inventors: Wylie W. Vale, Teresa M. Reyes, Paul E. Sawchenko, Jean E. Rivier, Kathy A. Lewis, John B. Hogenesch, Joan M. Vaughan, Marilyn H. Perrin
-
Patent number: 6399315Abstract: In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of ≦10 nM of CRF occupy ≧50% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. Invention CRF-Rs can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.Type: GrantFiled: June 7, 1995Date of Patent: June 4, 2002Assignee: The Salk Institute for Biological StudiesInventors: Marilyn H. Perrin, Ruoping Chen, Kathy A. Lewis, Wylie W. Vale, Jr., Cynthia J. Donaldson, Paul Sawchenko
-
Publication number: 20020055617Abstract: In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of £ 10 nM of CRF occupy 50% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. Invention CRF-Rs can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.Type: ApplicationFiled: November 12, 1998Publication date: May 9, 2002Inventors: MARILYN H. PERRIN, RUOPING CHEN, KATHY A. LEWIS, WYLIE W. VALE, CYNTHIA J. DONALDSON, PAUL SAWCHENKO
-
Patent number: 6353152Abstract: The present invention provides transgenic mice deficient in corticotropin releasing factor receptor 2. Corticotropin releasing factor is a critical integrator of the hypothalamic-pituitary-adrenal axis in response to stress. CRF and its related molecule urocortin bind CRF receptor 1 and CRFR2 with distinct affinities. CRFR2 mutant mice were hypersensitive to stress and displayed increased anxiety-like behavior. Mutant mice had normal basal feeding and weight gain, but exhibited decreased food intake following food deprivation. Intravenous UCN dramatically decreased the mean arterial pressure in the controls but had no effect in the mutants. A deficiency of CRFR2 results in a significant increase in urocortin mRNA in the rostral region of the Edinger Westphal and a significant increase in CRF mRNA in central nucleus of the amygdala. These results demonstrate that the CRFR2 mutant mice, opposed to CRFR1 mutant mice, have an increased sensitivity to stress and display anxiety-like behavior.Type: GrantFiled: July 14, 2000Date of Patent: March 5, 2002Assignee: Research Development FoundationInventors: Kuo-Fen Lee, Wylie W. Vale, Tracy L. Bale, George W. Smith
-
Publication number: 20010039036Abstract: In accordance with the present invention, there are provided novel receptor proteins characterized by having the following domains, reading from the N-terminal end of said protein:Type: ApplicationFiled: December 19, 2000Publication date: November 8, 2001Applicant: The Salk Institute for Biological Studies.Inventors: Lawrence S. Mathews, Wylie W. Vale, Kunihiro Tsuchida
-
Patent number: 6214797Abstract: Urocortin (Ucn) is a native mammalian peptide generally related to Urotensin I and Corticotropin Releasing Factor (CRF). Human Ucn has the formula: Asp-Asn-Pro-Ser-Leu-Ser-Ile-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Thr-Leu-Leu-Glu-Leu-Ala-Arg-Thr-Gln-Ser-Gln-Arg-Glu-Arg-Ala-Glu-Gln-Asn-Arg-Ile-Ile-Phe-Asp-Ser-Val-NH2 (SEQ ID NO:15). Rat-derived Ucn is identical but for 2 substitutions, Asp2 for Asn2 and Pro4 for Ser4. Ucn or analogs thereof or pharmaceutically acceptable salts can be administered to humans and other mammals to achieve substantial elevation of ACTH, &bgr;-endorphin, &bgr;-lipotropin, other products of the pro-opiomelanocortin gene and corticosterone. They can also be used to lower blood pressure over an extended period of time, as stimulants to elevate mood and to improve memory and learning performance, as well as diagnostically. Shortened fragments may be administered to release endogenous CRF and/or Ucn in the brain and peripherally.Type: GrantFiled: December 10, 1997Date of Patent: April 10, 2001Assignee: The Salk Institute for Biological StudiesInventors: Wylie W. Vale, Jr., Joan Vaughan, Cynthia J. Donaldson, Kathy A. Lewis, Paul Sawchenko, Jean E. F. Rivier, Marilyn H. Perrin
-
Patent number: 6166287Abstract: In accordance with the present invention, there are provided CRF overproducing transgenic mice which exhibit endocrine abnormalities involving the hypothalamic-pituitary-adrenal axis, such as elevated plasma levels of ACTH and glucocorticoids. The transgenic mice of the present invention represent a genetic model of CRF overproduction, providing a valuable tool for investigating the long term effects of CRF excess and dysregulation in the central nervous system.Type: GrantFiled: June 4, 1999Date of Patent: December 26, 2000Assignees: The Salk Institute for Biological Studies, The Scripp Research InstituteInventors: Wylie W. Vale, Jr., Mary P. Stenzel-Poore, George F. Koob, Stephen C. Heinrichs
-
Patent number: 6162896Abstract: In accordance with the present invention, there are provided novel receptor proteins characterized by having the following domains, reading from the N-terminal end of said protein:an extracellular, ligand-binding domain,a hydrophobic, trans-membrane domain, andan intracellular, receptor domain having serine kinase-like activity.The invention receptors optionally further comprise a second hydrophobic domain at the amino terminus thereof. The invention receptor proteins are further characterized by having sufficient binding affinity for at least one member of the activin/TGF-.beta. superfamily of polypeptide growth factors such that concentrations of .ltoreq.10 nM of said polypeptide growth factor occupy .gtoreq.50% of the binding sites of said receptor protein. A presently preferred member of the invention superfamily of receptors binds specifically to activins, in preference to inhibins, transforming growth factory-.beta., and other non-activin-like proteins.Type: GrantFiled: June 7, 1995Date of Patent: December 19, 2000Assignee: The Salk Institute for Biological StudiesInventors: Lawrence W. Mathews, Wylie W. Vale, Jr., Kunihiro Tsuchida
-
Patent number: 6023011Abstract: In accordance with the present invention, there are provided CRF overproducing transgenic mice which exhibit endocrine abnormalities involving the hypothalamic-pituitary-adrenal axis, such as elevated plasma levels of ACTH and glucocorticoids. The transgenic mice of the present invention represent a genetic model of CRF overproduction, providing a valuable tool for investigating the long term effects of CRF excess and dysregulation in the central nervous system.Type: GrantFiled: May 28, 1993Date of Patent: February 8, 2000Assignee: The Salk Insitute for Biological StudiesInventors: Wylie W. Vale, Jr., Mary P. Stenzel-Poore
-
Patent number: 5910428Abstract: Isolated, substantially pure mammalian brain-derived membrane-associated CRF-binding proteins and biologically active fragments thereof are provided as well as isolated and purified DNA fragments which encode the CRF binding proteins or biologically active fragments thereof or homologs of other mammalian species. By administering an amount of such CRF binding protein or a fragment thereof effective to modulate receptor activation, it is possible to modulate the action of CRF upon (a) the brain and nervous system, (b) the pituitary particularly for production of ACTH, beta endorphin and cortisol, (c) sites of inflammation, (d) the placenta, (e) the adrenal glands, (f) the gonads or (g) the gastrointestinal tract. Administration of an N-terminal fragment of the protein increases the binding site density for CRF and thus modulates its biological effect in vivo.Type: GrantFiled: July 2, 1996Date of Patent: June 8, 1999Assignee: The Salk Institute for Biological StudiesInventors: Dominic P. Behan, Wylie W. Vale, Jr., Wolfgang H. Fischer, Philip J. Lowry
-
Patent number: 5885794Abstract: In accordance with the present invention, there are provided novel receptor proteins characterized by having the following domains, reading from the N-terminal end of said protein:an extracellular, ligand-binding domain,a hydrophobic, trans-membrane domain, andan intracellular, receptor domain having serine kinase-like activity.The invention receptors optionally further comprise a second hydrophobic domain at the amino terminus thereof. The invention receptor proteins are further characterized by having sufficient binding affinity for at least one member of the activin/TGF-.beta. superfamily of polypeptide growth factors such that concentrations of .ltoreq.10 nM of said polypeptide growth factor occupy .gtoreq.50% of the binding sites of said receptor protein. A presently preferred member of the invention superfamily of receptors binds specifically to activins, in preference to inhibins, transforming growth factor-.beta., and other non-activin-like proteins.Type: GrantFiled: September 2, 1994Date of Patent: March 23, 1999Assignee: The Salk Institute for Biological StudiesInventors: Lawrence S. Mathews, Wylie W. Vale
-
Patent number: 5844080Abstract: A Corticotropin Releasing Factor-binding protein (CRF-BP) is isolated and purified sufficient to provide AA sequence data from which the DNA is obtained, which is then used to produce the protein recombinantly. The CRF-BP is useful for modulating the biological activity of CRF, such as reducing the high ACTH levels in mammals caused by excess CRF. The CRF-BP or fragments thereof and/or antibodies to the proteins may be employed in diagnostic assays to determine the levels of CRF, CRF-BP and the ratio of CRF/CRF-BP in a vascular fluid sample. The DNA or subsequence thereof can be used as probes for genetic material in certain assays. The anti-CRF-BP antibodies are also useful to purify the CRF-BP protein and to modulate the biological effect of CRF-BPs proteins.Type: GrantFiled: June 5, 1995Date of Patent: December 1, 1998Assignees: The Salk Institute for Biological Studies, The University of ReadingInventors: Ellen Potter, Dominic P. Behan, Wolfgang H. Fischer, Elizabeth A. Linton, Philip J. Lowry, Wylie W. Vale, Jr.
-
Patent number: 5733790Abstract: Corticotropin Releasing Factor-binding protein (CRF-BP) is produced recombinantly and is useful for modulating the biological activity of CRF. CRF-BP or fragments thereof and/or antibodies to such polypeptides are employed in diagnostic assays to determine the levels of CRF and CRF-BP and the ratio of CRF/CRF-BP in a vascular fluid sample. Following such an assay, pregnancy-related pathological disorders, such as increased risk of premature labor, can be treated, for example, by administering CRF-BP to lower the ratio of CRF/CRF-BP to within a normal range for pregnancy. Anti-CRF-BP antibodies are also useful to purify CRF-BP and to modulate the biological effect of CRF-BPs.Type: GrantFiled: June 7, 1995Date of Patent: March 31, 1998Assignees: The Salk Institute for Biological Studies, The University of ReadingInventors: Ellen Potter, Dominic P. Behan, Elizabeth A. Linton, Philip J. Lowry, Wylie W. Vale, Jr.
-
Patent number: 5728545Abstract: In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of .ltoreq.10 nM of CRF occupy .gtoreq.50% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. The invention CRF-R can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.Type: GrantFiled: August 23, 1993Date of Patent: March 17, 1998Assignee: The Salk Institute of Biological StudiesInventors: Marilyn H. Perrin, Ruoping Chen, Kathy A. Lewis, Wylie W. Vale, Jr., Cynthia J. Donaldson
-
Patent number: 5587462Abstract: Isolated, substantially pure mammalian brain-derived membrane-associated CRF-binding proteins and biologically active fragments thereof are provided as well as isolated and purified DNA fragments which encode the CRF binding proteins or biologically active fragments thereof or homologs of other mammalian species. By administering an amount of such CRF binding protein or a fragment thereof effective to modulate receptor activation, it is possible to modulate the action of CRF upon (a) the brain and nervous system, (b) the pituitary particularly for production of ACTH, beta endorphin and cortisol, (c) sites of inflammation, (d) the placenta, (e) the adrenal glands, (f) the gonads or (g) the gastrointestinal tract. Administration of an N-terminal fragment of the protein increases the binding site density for CRF and thus modulates its biological effect in vivo.Type: GrantFiled: November 8, 1993Date of Patent: December 24, 1996Assignee: The Salk Institute For Biological StudiesInventors: Dominic P. Behan, Wylie W. Vale, Jr., Wolfgang H. Fischer, Philip J. Lowry
-
Patent number: 5530095Abstract: Mammalian melanin-concentrating hormone (MCH) is isolated from rat tissue, purified and characterized. These MCH peptides are useful for treating skin disorders, for suppressing the proliferation of skin tumor cells, such as melanomas in mammals, and for modulating the secretion of ACTH. Generally, peptides are provided which have the following formula: ##STR1## or which are naturally occurring homologs of the peptide with said formula. The peptides which are the naturally occurring MCH homologs of mammalian species other than rat can also be obtained using the materials disclosed, as demonstrated specifically with human MCH, which is found to have the same structure as rat MCH. Also disclosed are the amino acid sequences of, and the nucleotide sequences of the cDNAs which encode, the putative precursors of rat MCH and human MCH. These precursors may also include one or more biologically active peptides N-terminally of the mature MCH's.Type: GrantFiled: May 23, 1995Date of Patent: June 25, 1996Assignee: The Salk Institute for Biological StudiesInventors: Joan Vaughn, Wolfgang H. Fischer, Jean E. F. Rivier, Jean-Louis M. Nahon, Francoise G. Presse, Wylie W. Vale, Jr.
-
Patent number: 5510458Abstract: Disclosed are improved CRF peptide antagonists such as those having the formula: Y-D-Phe-Xaa.sub.13 -Leu-Leu-Arg-Xaa.sub.17 -Xaa.sub.18 -Leu-Xaa.sub.20 -Nle-Xaa.sub.22 -Xaa.sub.23 -Xaa.sub.24 -Xaa.sub.25 -Xaa.sub.26 -Leu-Xaa.sub.28 -Xaa.sub.29 -Gln-Xaa.sub.31 -Xaa.sub.32 -Xaa.sub.33 -Xaa.sub.34 -Arg-Xaa.sub.36 -Xaa.sub.37 -Nle-Xaa.sub.39 -Xaa.sub.40 -Xaa.sub.41 -NH.sub.2 wherein Y is Ac or hydrogen; Xaa.sub.13 is His, Tyr or Glu; Xaa.sub.17 is CML, Glu, Asn or Lys; Xaa.sub.18 is Val, Nle or Met; Xaa.sub.20 is Glu, D-Glu, Aib or D-Ala; Xaa.sub.22 is Ala, Aib, Thr, Asp or Glu; Xaa.sub.23 is Arg, Orn, Har or Lys; Xaa.sub.24 is Ala or Aib; Xaa.sub.25 is Asp or Glu; Xaa.sub.26 is Gln, Asn or Lys; Xaa.sub.28 is Ala or Aib; Xaa.sub.29 is Gln, Aib or Glu, Xaa.sub.31 is Ala or Aib; Xaa.sub.32 is His, Aib, Gly, Tyr or Ala; Xaa.sub.33 is Ser, Aib, Asn, Leu, Thr or Ala; Xaa.sub.34 is Asn or Aib; Xaa.sub.36 is Lys, Orn, Arg, Har or Leu; Xaa.sub.37 is Leu or Tyr; Xaa.sub.39 is Glu, Aib or Asp; Xaa.sub.Type: GrantFiled: December 14, 1993Date of Patent: April 23, 1996Assignee: The Salk Institute For Biological StudiesInventors: Wayne D. Kornreich, Jean F. Hernandez, Jean E. Rivier, Catherine L. Rivier, Wylie W. Vale, Jr.
-
Patent number: 5493006Abstract: Improved CRF peptide antagonists have the formula: ##STR1## wherein R.sub.20 is Cys or Glu; R.sub.23 is Cys, Lys or Orn; provided that when R.sub.20 is Cys, R.sub.23 is Cys and when R.sub.20 is Glu, R.sub.23 is Lys or Orn; or a nontoxic addition salt thereof. Specific CRF antagonists disclosed include (cyclo 20-23) [D-Phe.sup.12, Lys.sup.23, Nle.sup.21,38, ]rCRF(12-41); (cyclo 20-23) [D-Phe.sup.12, Orn.sup.23, Nle.sup.21,38 ]rCRF(12-41) and (cyclo 20-23) [D-Phe.sup.12, Cys.sup.20, Cys.sup.23, Nle.sup.21,38 ]rCRF(12-41).Type: GrantFiled: June 16, 1993Date of Patent: February 20, 1996Assignee: The Salk Institute for Biological StudiesInventors: Antonio de Miranda, Wylie W. Vale, Jr., Jean E. F. Rivier, Catherine L. Rivier