Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
2006-05-03
2008-11-18
Ulm, John D (Department: 1649)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C435S007210, C436S501000
Reexamination Certificate
active
07452682
ABSTRACT:
The invention is directed to a method for identifying substances acting as ligands for transfected receptors by using transfected markers to measure receptor/ligand interactions. The present invention also relates to a method of identifying compounds which act as inverse agonists of the 5-HT2A receptor, the method comprising contacting a constitutively active 5-HT2A receptor with at least one test compound and determining any decrease in the amount of basal activity of the receptor so as to identify a test compound which is an inverse agonist of the 5-HT2A receptor. Such inverse agonists may be used in the treatment of schizophrenia and related psychoses.
REFERENCES:
patent: 5071773 (1991-12-01), Evans et al.
patent: 5071858 (1991-12-01), Hutchison
patent: 5401629 (1995-03-01), Harpold et al.
patent: 5635528 (1997-06-01), Audia et al.
patent: 5661024 (1997-08-01), Kao et al.
patent: 5707798 (1998-01-01), Brann
patent: 5912132 (1999-06-01), Brann
patent: 5955281 (1999-09-01), Brann
patent: 6107324 (2000-08-01), Behan et al.
patent: 6358698 (2002-03-01), Weiner et al.
patent: 0 244 221 (1987-11-01), None
patent: 0 371 820 (1990-06-01), None
patent: WO 92/01810 (1990-02-01), None
patent: WO 92/05244 (1992-04-01), None
patent: WO 93/23431 (1993-11-01), None
patent: WO 95/02823 (1995-01-01), None
patent: WO 95/06117 (1995-03-01), None
patent: WO 96/17081 (1996-06-01), None
patent: WO 97/21731 (1997-06-01), None
patent: WO 97/38991 (1997-10-01), None
patent: WO 97/39001 (1997-10-01), None
patent: WO 98/38217 (1998-09-01), None
patent: WO 99/52927 (1999-10-01), None
Trueheart et al., Two Genes Required for Cell Fusion during Yeast Conjugation: Evidence for a Pheromone-Induced Surface Protein, Jul. 1987, Molecular and Cellular Biology 7(7):2316-2328.
Dietzel et al., The Yeast SCG1 Gene: A G-alpha-like Protein Implicated in the A- and alpha-Factor Response Pathway, Sep. 25, 1987, Cell 50:1001-1010.
Barker, et al., “Constitutively Active 5-Hydroxytryptamine2CReceptor Reveal Novel Inverse Agonist Activity of Receptor Ligands”,J. of Biological Chemistry, (Apr. 22, 1994) 269(16):11687-11690.
Barr, et al, “Agonist-independent Activation of Gzby the 5-Hydroxytryptamine1AReceptor Co-expressed inSpodoptera frugiperdaCells”,J. of Biological Chemistry, (Dec. 26, 1997) 272(52):32979-32987.
Benes, et al, “Altered Neural Circuits in Schizophrenia”,The Harvard Mental Health Letter, Nov. 1996, 13(5).
Buckland, et al., “The effects of antipsychotic drugs on the mRNA levels of serotonin 5HT2Aand 5HT2Creceptors”,Molecular Brain Research, (1997) 48:45-52.
Burnet, et al., “The Effects of Clozapine and Haloperidol on Serotonin-1A, -2A and -2C Receptor Gene Expression and Serotonin Metabolism in the Rat Forebrain”,Neuroscience, (1996) 73(2):531-540.
Casey, et al., “Constitutively active mutant 5HT2Areceptors”,Society for Neuroscience Abstracts, (1996) 22(3):699-710.
Charpentier, et al., “Silencing of the Constitutive Activity of the Dopamine D1B Receptor”,J. Biological Chemistry, (Nov. 8, 1996) 271(45):28071-28076.
Chidiac, et al., “Inverse Agonist Activity of β-Adrenergic Antagonists”,Molecular Pharmacology, 45:490-499, (Mar. 1994).
Costa, et al., “Antagonists with negative intrinsic activity at d opioid receptors coupled to GTP-binding proteins”,Biochemistry, (Oct. 1989) 86:7321-7325.
Costa, et al., “Drug Efficacy at Guanine Nucleotide-Binding Regulatory Protein-Linked Receptors: Thermodynamic Interpretation of Negative Antagonism and of Receptor Activity in the Absence of Ligand”,Molecular Pharmacology, 41:549-560, (Mar. 1992).
Egan, et al., “Creation of a constitutively activated state of the 5HT2Areceptor by site-directed mutagenesis: revelation of inverse agonist activity of antagonists”,Annals NY Acad. Sci., (1998) 861:136-139.
Egan, et al., “Creation of a constitutively activated state of the 5-hydroxytryptamine2Areceptor by site-directed mutagenesis: inverse agonist activity of antipsychotic drugs,”JPET, (1998) 286:85-90.
Eggericks, et al., “Molecular cloning of an orphan G-protein-coupled receptor that constitutively activates adenylate cyclase”,Biochemcial J., (1995) 309:837-843.
Ferry, et al., “Effects of Agonists, Partial Agonists, and Antagonists on the Regulation of 5-Hydroxytryptamine2Receptors in P11 Cells”,Molecular Pharmacology, 43:726-733, (May 1993).
Frazier, et al., “The Brains of Schizophrenic Children”,The Harvard Mental Health Letter, Feb. 1997.
Garver, David L., “Is Schizophrenia a Degenerative or a Developmental Disorder?”,The Harvard Mental Health Letter, Aug. 1997.
Gethert, et al., “Structural Instability of a Constitutively Active G Protein-coupled Receptor”,J. Biological Chemistry, (Jan. 31, 1997) 272(5):2587-2590.
Goldberg, et al., “Cognitive Loss in Schizophrenia”,The Harvard Mental Health Letter, Apr. 1991.
Griffon, et al., “Antipsychotics with inverse agonist activity at the dopamine D3receptor”,J. Neural Transmission, (1996) 103:1163-1175.
Groteweil, et al., “Receptors exhibit constitutive activity that is blocked by inverse agonist”,FASEB J., (1994) 8:A1319.
Gutkind, et al., “Muscarinic acetylcholine receptor subtypes as agonist-dependent oncongenes”,Proc. Natl. Acad. Sci. USA, (Jun. 1991) 88:4703-4707.
Hanson, et al., “Comparison of Neurotensin Responses to MDL 100,907, a Selective 5HT2AAntagonist, with Clozapine and Haloperidol”,Brain Research Bulletin, (1997) 42(3):211-219.
Hartman, et at., “Functional Reconstitution in Situ of 5-Hydroxytryptamine2C(5HT2C) Receptors with aqand Inverse Agonism of 5HT2CReceptor Antagonists”,J. Biological Chemistry, (Sep. 13, 1996) 371(37):22591-22597.
Himmler, et al., “Functional Testing of Human Dopamine D1and D5Receptors Expressed in Stable cAMP-Response Luciferase Reporter Cell Lines”,J. Receptor Research, (1993) 13(1-4):79-94.
Hudson, et al., “Identification and characterization of a regulated promoter element in the epidermal growth factor receptor gene”,Proc. Natl. Acad. Sci. USA, (Oct. 1990) 87:7536-7540.
International Search Report for application PCT/US99/21439, mailed on Mar. 17, 2000.
Julius, et al., “The 5HT2 Receptor Defines a Family of Structurally Distinct but Functionally Conserved Serotonin Receptors”,Proc. Natl. Acad. Sci. USA, (Feb. 1990) 87:928-932.
Kehne, et al., “Preclinical characterization of the potential of the putative atypical antipsycholic MDL 100,907 as a potent 5HT2Aantagonist with a favorable NCS safety profile”,JPET, (1996) 277:968-981.
Labrecque, et al., “Serotonergic Antagonists Differentially Inhibit Spontaneous Activity and Decrease Ligand Binding Capacity of the Rat 5-Hydroxytryptamine Type 2C Receptor in Sf9 Cells”,Molecular Pharmacology, (1995) 48:150-159.
Lefkowitz, et al., “Constitutive activity of receptors coupled to guanine nucleotide regulatory proteins”,Elsevier Science Publishers, (Aug. 1993) 14:303-307.
Lefkowitz, Robert J., “Turned on to ill effect”,Nature, (Oct. 14, 1993) 365:603.
Leysen, et al., “Interaction of antipsychotic drugs with neurotransmitter receptor sites in vitro and in vivo in relation to pharmacological and clinical effects: role of 5HT2receptors”,Psychopharmacology, (1993) 112:S40-S54.
Meltzer, et al, “VII. Effects of Antipsychotic Drugs on Serotonin Receptors”,Pharmacological Reviews, (1991) 43(4):587-604.
Milligan, et al, “Inverse agonism: pharmacological curiosity or potential therapeutic strategy?”,TiPS, (Jan. 1995) 16:10-13.
Newman-Tancredi, et al., “Agonist and Antagonist Actions of (-)Pindolol at Recombinant, Human Serotonin1A(5-HT1A) Receptors”,Neuropsychopharmacology, (1998) 18(5):396-398.
Newman-Tancredi, et al., “Agonist and Inverse Agonist Efficacy at Human Recombinant Serotoni
Acadia Pharmaceuticals Inc.
Knobbe Martens & Olson Bear LLP.
Ulm John D
LandOfFree
Identification of 5HT2A receptor ligands by selective... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Identification of 5HT2A receptor ligands by selective..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Identification of 5HT2A receptor ligands by selective... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-4028050