Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
1999-05-17
2001-04-24
Low, Christopher S. F. (Department: 1653)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S023100, C536S023500, C536S025100, C536S024310, C514S002600, C514S012200, C435S069520, C435S252300, C435S007100, C435S006120, C435S320100, C435S007200, C435S091300, C435S803000, C530S350000, C530S300000, C530S387100, C436S094000, C436S808000, C436S811000, C436S501000
Reexamination Certificate
active
06222027
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to polynucleotides comprising at least a fragment of genes expressed in hippocampus. The invention also relates to the use of these molecules in diagnosis, prognosis, prevention, treatment, and evaluation of therapies for diseases associated with the hippocampus such as Alzheimer's disease, Huntington's disease, schizophrenia, epilepsy, and their complications.
BACKGROUND OF THE INVENTION
The hippocampus is part of the brain's limbic system which controls emotional behavior, motivational drive, and other physiological functions. The limbic system includes the limbic cortex, hippocampus, amygdala, hypothalamus, and anterior thalamus. The hippocampus plays an important role in learning processes and certain types of memory. Stimulation of the hippocampus can cause behavioral responses including rage, passivity, and excess sex drive. Weak electrical stimulation can cause hippocampal seizures. Individuals who lose hippocampal function retain memory for events that occurred prior to the loss and only have immediate memory, lasting less than a few minutes, for all events after the loss (anterograde amnesia). Thus, the hippocampus is thought to interpret the importance of incoming sensory information and to determine what input is worth remembering. The hippocampus then transmits signals that make the mind rehearse the information over and over again until permanent storage takes place.
Numerous studies of the effects of ablation of the hippocampus of rodent, primate, and other non-human species have been conducted. Memory disorders and spatial performance are associated with hippocampal function. Morphological changes in the hippocampus, including cell loss, is associated with epilepsy, schizophrenia, Alzheimer's disease, and certain amnesiac syndromes. (Jack (1994)
Epilepsia
35:S21-S29). Research data from animals show glucocorticoids secreted during stress can damage the hippocampus and impair the ability of hippocampal neurons to survive neurological insults. (Sapolsky (1993)
Behav. Brain Res.
57:175-82). Sustained glucocorticoid exposure might damage the hippocampus in humans as well; hippocampal atrophy has been reported in patients with Cushing's syndrome as a result of the hypersecretion of glucocorticoids.
Phylogenetic relationships among organisms have been demonstrated many times, and studies from a diversity of prokaryotic and eukaryotic organisms suggest a more or less gradual evolution of biochemical and physiological mechanisms and metabolic pathways. Despite different evolutionary pressures, proteins that regulate the cell cycle in yeast, nematode, fly, rat, and man have common chemical or structural features and modulate the same general cellular activity. Comparisons of human gene sequences with those from other organisms where the structure and/or function may be known allow researchers to draw analogies and to develop model systems for testing hypotheses. These model systems are of great importance in developing and testing diagnostic and therapeutic agents for human conditions, diseases and disorders.
Identification of genes that participate in hippocampal development provide new potential diagnostic and therapeutic targets. The present invention satisfies a need in the art by providing new compositions that are useful for diagnosis, prognosis, treatment, prevention, and evaluation of therapies for diseases associated with hippocampus such as Alzheimer's disease, Huntington's disease, schizophrenia, epilepsy, and their complications.
SUMMARY OF THE INVENTION
In one aspect, the invention provides for substantially purified polynucleotides expressed in hippocampus. Preferred embodiments include (a) a polynucleotide sequence of SEQ ID NOs:1-7; (b) a polynucleotide sequence which encodes the polypeptide sequence of SEQ ID NO:8; (c) a polynucleotide sequence having at least 70% identity to the polynucleotide sequence of (a) or (b); (d) a polynucleotide sequence which is complementary to the polynucleotide sequence of (a), (b), or (c); (e) a polynucleotide sequence comprising at least 10, preferably at least 18, sequential nucleotides of the polynucleotide sequence of (a), (b), (c), or (d); and (f) a polynucleotide which hybridizes under stringent conditions to the polynucleotide of (a), (b), (c), (d) or (e). Furthermore, the invention provides an expression vector comprising any of the above described polynucleotides and host cells comprising the expression vector. Still further, the invention provides a method for treating or preventing a disease or condition associated with the altered expression of a gene that is expressed in hippocampus comprising administering to a subject in need a polynucleotide described above in an amount effective for treating or preventing the disease.
In a second aspect, the invention provides a substantially purified polypeptide comprising the gene product of a gene that is expressed in hippocampus. Preferred embodiments are (a) the polypeptide sequence of SEQ ID NO:8; (b) a polypeptide sequence having at least 85% identity to the polypeptide sequence of (a); and (c) a polypeptide sequence comprising at least 6 sequential amino acids of the polypeptide sequence of (a) or (b). Additionally, the invention provides antibodies that bind specifically to the above described polypeptide and a method for treating or preventing a disease or condition associated with the altered expression of a gene that is expressed in hippocampus comprising administering to a subject in need such an antibody in an amount effective for treating or preventing the disease.
In another aspect, the invention provides a pharmaceutical composition comprising any one of the polynucleotides or polypeptide described above in conjunction with a suitable pharmaceutical carrier and a method for treating or preventing a disease or condition associated with the altered expression of a gene that is expressed in hippocampus comprising administering to a subject in need such a composition in an amount effective for treating or preventing the disease.
In a further aspect, the invention provides a method for diagnosing a disease or condition associated with the altered expression of a gene that is expressed in hippocampus. The method comprises the steps of (a) providing a sample comprising one or more of the expressed genes; (b) hybridizing one or more of the polynucleotides described above to the expressed genes under conditions effective to form one or more hybridization complexes; (c) detecting the hybridization complexes; and (d) comparing the levels of the hybridization complexes with the level of hybridization complexes in a nondiseased sample, wherein altered levels of one or more of the hybridization complexes in a diseased sample compared with the level of hybridization complexes in a non-diseased sample correlates with the presence of the disease or condition.
The invention also provides a method for using a nucleic acid sequence or a fragment thereof to screen a library of molecules to identify at least one molecule which specifically binds the nucleic acid sequence, the method comprising providing a library of molecules, combining the nucleic acid sequence with the library of molecules under conditions suitable to allow specific binding, and detecting specific binding, thereby identyfying a molecule which specifically binds the nucleic acid sequence. Such libraries include DNA and RNA molecules, peptides, PNAs, proteins, and the like which are potential regulators of replication, transcription, and translation. The invention also provides a method for using a protein or a portion thereof to screen a library of molecules to identify at least one molecule which specifically binds the protein, the method comprising providing a library of molecules, combining the protein with the library of molecules under conditions suitable to allow specific binding, and detecting specific binding, thereby identifying a molecule which specifically binds the protein. In one aspect, a molecule identif
Azimzai Yalda
Baughn Mariah R.
Kaser Matthew R.
Lal Preeti
Tang Y. Tom
Incyte Genomics Inc.
Incyte Genomics, Inc.
Low Christopher S. F.
Robinson Hope A.
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