Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Testing efficacy or toxicity of a compound or composition
Reexamination Certificate
2000-11-22
2004-05-04
Padmanabhan, Sreeni (Department: 1617)
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
Testing efficacy or toxicity of a compound or composition
C424S009100
Reexamination Certificate
active
06730287
ABSTRACT:
BACKGROUND OF THE INVENTION
Sleep is a naturally occurring, periodic, reversible state of unconsciousness that is ubiquitous in mammals and birds, although its precise function is not known. The importance of sleep is suggested by its homeostatic regulation: the longer an animal is awake, the more it needs to sleep.
In humans, obtaining less than the required number of hours of sleep, particularly over several nights, leads to a decreased ability to retain new information, impaired productivity, altered mood, lowered resistance to infection and an increased susceptibility to accidents. Sleep-related traffic accidents annually claim thousands of lives, and operator fatigue has also been shown to play a contributory role in airplane crashes and other catastrophic accidents.
Besides lifestyle factors, a variety of physiological and psychological disorders can affect sleep patterns. The most common sleep disorder is primary insomnia, or a difficulty in initiating or maintaining sleep, which affects a large percentage of the population at some point in their lives. Other common sleep disorders include hypersomnia, or excessive daytime sleepiness, and narcolepsy, which is characterized by sudden and irresistible bouts of sleep.
Currently available drugs used to modulate vigilance, such as drugs that induce sleep, prolong wakefulness, or enhance alertness, suffer from a number of shortcomings. For example, available sleep-inducing drugs often do not achieve the fully restorative effects of normal sleep. Often such drugs cause undesirable effects upon waking, such as anxiety or continued sedation. Many available drugs that increase vigilance do so with a characteristic “crash” when the effect of the drugs wears off. Furthermore, many of the currently available drugs that modulate sleep and wakefulness are addictive or have adverse effects on learning and memory.
Clearly, there is a need to identify drugs that induce restorative sleep or that increase vigilance, without undesirable side effects. Unfortunately, current methods for screening for such drugs, using mammals, are slow, burdensome and expensive. Thus, there exists a need for improved methods for screening for drugs that modulate sleep and vigilance. The present invention satisfies this need and provides related advantages as well.
SUMMARY OF THE INVENTION
The invention provides a method of identifying a compound that alters vigilance. The method consists of contacting an invertebrate with a candidate compound, evaluating a vigilance property in the contacted invertebrate, and determining if the candidate compound alters the vigilance property in the contacted invertebrate. A candidate compound that alters the vigilance property in the contacted invertebrate is identified as a compound that alters vigilance.
In one embodiment, the vigilance property evaluated is a behavioral property, including activity, latency to sleep or arousal threshold. In another embodiment, the vigilance property evaluated is a molecular property, including expression of one or more vigilance-modulated genes.
The invention also provides a method of identifying a vigilance enhancing compound that modulates homeostatic regulation. The method consists of contacting an invertebrate with a compound that increases vigilance, and determining the effect of the compound on a homeostatic regulatory property of vigilance. A compound that alters the homeostatic regulatory property is characterized as being a vigilance enhancing compound that modulates homeostatic regulation.
Also provided is a method of identifying a vigilance diminishing compound that modulates homeostatic regulation. The method consists of contacting an invertebrate with a compound that decreases vigilance, and determining the effect of the compound on a homeostatic regulatory property of vigilance. A compound that alters the homeostatic regulatory property is characterized as being a vigilance diminishing compound that modulates homeostatic regulation.
REFERENCES:
patent: 5885831 (1999-03-01), Young et al.
patent: 5968817 (1999-10-01), Sutcliffe et al.
patent: 6436628 (2002-08-01), Young et al.
patent: 0 890 578 (1999-01-01), None
patent: 10502336 (1998-03-01), None
patent: 09804125 (1999-03-01), None
patent: WO 99/24610 (1999-05-01), None
patent: WO 99/57137 (1999-11-01), None
Inouéet al., “Behavior-Modulating Effects of Uridine in the Rhinoceros beetle”,Zoological Science3:727-729 (1986).
Andretic et al., “Requirement of circadian genes for cocaine sensitization in drosphilia,”Science285:1066-1068 (1999).
Boynton et al., “Latheo a new gene involved in associative learning and memory in drosophila-,elanogaster identified from P element mutagenesis,”Genetics131:655-672 (1992).
Chemelli et al., “Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation,”Cell98:437-451 (1999).
Cirelli et al., “Modulation of desynchronized sleep through microinjection of alpha-1-adrenergic agonists and antagonists in the dorsal pontine tegmentum of the cat,”Pflugers Archiv422:273-279 (1992).
Cirelli et al., “Difference in brain gene expression between sleep amd waking as revealed by mRNA differential display and cDNA microarray technology,”J. Sleep Research8:44-52 (1999).
Inoue et al., “Behavior-modulating effects of uridine in the rhinoceros beetle allomyrina-dichotoma,”Zoological Science(Tokyo) 3:727-730 (1986). (Abstract only).
Ishida et al., “Biological Clocks,”Prod. Natl. Acad. Sci. USA96: 8819-8820 (1999).
Michaud et al., “Mild insomnia induced by environmental perturbations in the rat a study of this new model and of its possible application in pharmacological research,”Arch. int. Pharmacodyn259:93-105 (1982).
Rankin et al., “Caenorhabditis-elegans a new model system for the study of learning and memory,”Behavioral Brain Research37:89-92 (1990).
Anderson, “Human Gene Therapy,”Nature392:25-30 (1998).
Aronstein et al., “Distribution of two GABA receptor-like subunits in the Drosophila CNS,”Invert. Neurosci.2:115-120 (1996).
Aston-Jones et al., “Activity of Norepinephrine-Containing Locus Coeruleus Neurons in Behaving Rates Anticipates Fluctuations in The Sleep-Waking Cycle,”Journal of Neuroscience1(8) :876-886 (1981).
Bellen, “The Fruit Fly: A Model Organism to Study the Genetics of Alcohol Abuse and Addiction?,”Cell93:909-912 (1998).
Belvin et al., “TheDrosophiladCREB2 Gene Affects the Circadian Clock,”Neuron22:777-797 (1999).
Bennett and van Dyke, “Improved food medium,”Dros. Inform. Serv.46:160 (1971).
Bliwise,Principles and Practice of Sleep MedicineKryger et al. Eds. (Saunders, Philadelphia, 2nded., Chapter 3 (1994).
Boynton and Tully, “latheo, a New Gene Involved in Associative Learning and Memory inDrosphila melanogaster, Identified fromPElement Mutagenesis,”Genetics131:655-672 (1992).
Brodbeck et al., “Molecular and Biochemical Characterization of theaaNAT1(Dat) Locus inDrosophila melanogaster: Differential Expressionof Two Gene Products, ”DNA and Cell Biology17:621-633 (1998).
Chemelli et al, “Naracolepsy inorexinKnockout Mice: Molecular Genetics of Sleep Regulation,”Cell98:437-451 (1999).
Cirelli and Tononi, “Changes in Gene Expressionin the Cerebral Cortex of Rats After Short- and Long-Term Total Sleep Deprivation,”Sleep22 (S) :113 (1999).
Cirelli et al., “Differences in gene expression during sleep and wakefulness,”Ann. Med.31:117-124 (1999).
Cirelli et al., “Differences in Gene Expression Between Sleep and Waking as Revealed by mRNA Differential Display,”Molecular Brain Research56:293-305 (1998).
Clark, “Genetics Components of Variation in Energy Storage inDrosphila Melanogaster,”Evolution44:637-650 (1990).
Connolly, “Locomotor Activity inDrosphilaas a Function of Food Deprivation,”Nature209:224 (1966).
Cortelli et al., “Fatal familial insomnia: clinical features and molecular genetics, ”J. Sleep Res. 8(S) :23-29 (1999).
Dijk et al., “Ageing and the circadian and homeostatic regulation of human sleep during forced desynchrony of rest, melatonin and temperature rhythms, ”Journal of Physiology516:611-627 (1999).
Dudai, “Inhibitors of Phosphodiesterase Affect Behavioral Pla
Cirelli Chiara
Greenspan Ralph J.
Shaw Paul J.
Tononi Giulio
McDermott & Will & Emery
Neurosciences Research Foundation Inc.
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