Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving hydrolase
Reexamination Certificate
2002-04-16
2003-08-19
Nashed, Nashaat T. (Department: 1650)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving hydrolase
C536S023200, C435S183000, C435S232000
Reexamination Certificate
active
06607895
ABSTRACT:
1. INTRODUCTION
The present invention relates to the discovery, identification, and characterization of novel human polynucleotides encoding a protein sharing sequence similarity with mammalian synthetases. The invention encompasses the described polynucleotides, host cell expression systems, the encoded protein, fusion proteins, polypeptides and peptides, antibodies to the encoded proteins and peptides, and genetically engineered animals that either lack or overexpress the disclosed genes, antagonists and agonists of the proteins, and other compounds that modulate the expression or activity of the proteins encoded by the disclosed genes, which can be used for diagnosis, drug screening, clinical trial monitoring, the treatment of diseases and disorders, and cosmetic or nutriceutical applications.
2. BACKGROUND OF THE INVENTION
Synthetases are enzymes that participate in the production of chemical compounds in the cell. Synthetases have been associated with, inter alia, regulating development, modulating cellular processes, and signal transduction.
3. SUMMARY OF THE INVENTION
The present invention relates to the discovery, identification, and characterization of nucleotides that encode a novel human protein, and the corresponding amino acid sequence of this protein. The novel human synthetase (NHS) described for the first time herein is a adenylsuccinate synthetase that shares structural similarity with animal synthetases, particularly adenylsuccinate synthetase (REFSEQ accession number: XM058642, which is herein incorporated by reference in its entirety), the enzyme that catalyzes the first step in the production of AMP from IMP.
The novel human nucleic acid (cDNA) sequence described herein encodes a protein/open reading frame (ORF) of 457 amino acids in length (see SEQ ID NO: 2).
The invention also encompasses agonists and antagonists of the described NHSs, including small molecules, large molecules, mutant NHSs, or portions thereof, that compete with native NHS, peptides, and antibodies, as well as nucleotide sequences that can be used to inhibit the expression of the described NHSs (e.g., antisense and ribozyme molecules, and open reading frame or regulatory sequence replacement constructs) or to enhance the expression of the described NHSs (e.g., expression constructs that place the described polynucleotide under the control of a strong promoter system), and transgenic animals that express a NHS sequence, or “knock-outs” (which can be conditional) that do not express a functional NHS. Knock-out mice can be produced in several ways, one of which involves the use of mouse embryonic stem cells (“ES cells”) lines that contain gene trap mutations in a murine homolog of at least one of the described NHSs. When the unique NHS sequences described in SEQ ID NOS:1-2 are “knocked-out” they provide a method of identifying phenotypic expression of the particular gene as well as a method of assigning function to previously unknown genes. In addition, animals in which the unique NHS sequences described in SEQ ID NOS:1-2 are “knocked-out” provide a unique source in which to elicit antibodies to homologous and orthologous proteins which would have been previously viewed by the immune system as “self” and therefore would have failed to elicit significant antibody responses. To these ends, gene trapped knockout ES cells have been generated in murine homologs of the described NHSs.
Additionally, the unique NHS sequences described in SEQ ID NOS:1-2 are useful for the identification of protein coding sequence and mapping a unique gene to a particular chromosome. These sequences identify actual, biologically verified, and therefore relevant, exon splice junctions as opposed to those that may have been bioinformatically predicted from genomic sequence alone. The sequences of the present invention are also useful as additional DNA markers for restriction fragment length polymorphism (RFLP) analysis, and in forensic biology.
Further, the present invention also relates to processes for identifying compounds that modulate, i.e., act as agonists or antagonists, of NHS expression and/or NHS activity that utilize purified preparations of the described NHSs and/or NHS product, or cells expressing the same. Such compounds can be used as therapeutic agents for the treatment of any of a wide variety of symptoms associated with biological disorders or imbalances.
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Cullinan Emily B.
Miranda Maricar
Yu Xuanchuan
Lexicon Genetics Incorporated
Nashed Nashaat T.
Swope Sheridan L.
LandOfFree
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