Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
1997-11-14
2002-04-23
Myers, Carla J. (Department: 1655)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C435S069100, C435S071100, C435S252300, C435S320100, C435S455000, C536S023100, C536S023500, C536S024310, C536S024330, C514S04400A
Reexamination Certificate
active
06376174
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to nucleic acids and proteins encoded thereby. Invention nucleic acids encode novel Schwannomin-Binding-Proteins. The invention also relates to methods for making and using such nucleic acids and proteins.
BACKGROUND OF THE INVENTION
The NF2 gene is the single most commonly mutated gene in benign tumors of the human nervous system. It is involved in the pathogenesis of virtually all schwannomas and many meningiomas (at least 50%) and ependymomas (Sainz et al.,
Hum. Mol. Genet.
3:885-891 (1994), Deprez et al.,
Am. J. Hum. Genet.
54:1022-1029 (1994), Rubio et al.,
Cancer Res.
54:45-47 (1994), Ruttledge et al,
Nature Genet.
6:180-184 (1994), and Slavo et al.,
Cancer
64:243-247 (1995)). In addition to tumors, NF2 germline mutations also give rise to cataracts and retinal abnormalities such as hamartomas (Mautner et al.,
Neurosurgery
38:880-886 (1996)). The NF2 gene product is schwannomin (or merlin). Schwannomin is structurally similar to the ezrin-radixin-moesin (ERM) family of membrane-organizing proteins that link the plasma membrane and cytoskeleton (Rouleau et al.,
Nature
363:515-521 (1993) and Trofatter et al.,
Cell
72:791-800 (1993)). Schwannomin functions as a tumor suppressor, and as such is thought to have a role in a signal transduction pathway (Sainz et al., (1994), Huynh and Pulst,
Oncogene
13:73-84 (1996), Tikoo et al.,
J. Biol. Chem.
269:23387-23390 (1994), and Twist et al.,
Hum. Mol. Genet.
3:147-151 (1994)). But other than its role in cell morphogenesis and adhesion (Huynh and Pulst (1996), supra), there is little additional knowledge of schwannomin function.
Therefore, there continues to be a need in the art for the discovery of additional proteins that interact with schwannomin, such as proteins that bind schwannomin in vivo, and especially a need for information serving to specifically identify and characterize such proteins in terms of their amino acid sequence. Moreover, to the extent that such molecules might form the basis for the development of therapeutic and diagnostic agents, it is essential that the DNA encoding them be elucidated. The present invention satisfies this need and provides related advantages as well.
BRIEF DESCRIPTION OF THE INVENTION
In accordance with the present invention, there are provided novel isolated nucleic acids encoding Schwannomin-Binding-Proteins (SBPs). Further provided are vectors containing invention nucleic acids, probes that hybridize thereto, host cells transformed therewith, antisense-nucleic acids thereto and related compositions. The nucleic acid molecules described herein can be incorporated into a variety of expression systems known to those of skill in the art. In addition, the nucleic acid molecules of the present invention are useful as probes for assaying for the presence and/or amount of a SBP gene or mRNA transcript in a given sample. The nucleic acid molecules described herein, and oligonucleotide fragments thereof, are also useful as primers and/or templates in a PCR reaction for amplifying genes encoding SBPs.
In accordance with the present invention, there are also provided isolated mammalian SBPs. These proteins, or fragments thereof, are useful in bioassays, as immunogens for producing anti-SBP antibodies, or in therapeutic compositions containing such proteins and/or antibodies. Also provided are transgenic non-human mammals that express the invention protein.
Antibodies that are immunoreactive with invention SBPs are also provided. These antibodies are useful in diagnostic assays to determine levels of SEPs present in a given sample, e.g., tissue samples, Western blots, and the like. The antibodies can also be used to purify SBPs from crude cell extracts and the like. Moreover, these antibodies are considered therapeutically useful to counteract or supplement the biological effect of SBPs in vivo.
Methods and diagnostic systems for determining the levels of SBP protein in various tissue samples are also provided. These diagnostic methods can be used for monitoring the level of therapeutically administered SBP or fragments thereof to facilitate the maintenance of therapeutically effective amounts. These diagnostic methods can also be used to diagnose physiological disorders that result from abnormal levels of SBP.
REFERENCES:
Dorsey et al. Molecular Biology of the Cell. 7, p23A, abstract #137, Dec. 1996.*
Chang et al. Genomics. 17:287-293, 1993.*
Wei et al. Nucleic Acids Research. 24:931-937, Feb. 1996.*
USB Catalog. Molecular Biologiy Reagents, p. 166, 1990.*
Asano et al. GenBank Accession No. U46025, Dec. 1996.*
Adams et al. GenBank Accession No. AA314857, Apr. 1997.*
Adams et al. GenBank Accession No. AA305985, Apr. 1997.*
Discher et al., “Mechanochemistry of the Alternatively Spliced Spectrin-Actin Binding Domain in Membrane Skeletal Protein 4.1”,J. Biol. Chem.,268(10):7186-7195 (1993).
Fields and Song, “A novel Genetic system to detect protein-protein interactions”,Nature,340:245-246 (1989).
Fox et al., “On the Role of the Platelet Membrane Skeleton in Mediating Signal Trnsduction”,J. Biol. Chem.,268(34):25973-25984 (1993).
Nelson et al., “Identification of a Membrane-Cytoskeletal Complex Containing the Cell Adhesion Molecule Uvomorulin (E-Cadherin), Ankyrin, and Fodrin in Madin-Darby Canine Kidney Epithelial Cells”,J. Cell. Biol.,110:349-357 (1990).
Rouleau et al., “Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2”,Nature,363:515-521 (1993).
Sainz et al., “Mutations of the neurofibromatosis type 2 gene and lack of the gene product in vestibular schwannomas”,Human Mol. Genet.,3(6):885-891 (1994).
Subrahmanyam et al., “Phosphorylation of protein 4.1 on tyrosine-418 modulates its function in vitro”,PNAS USA,88:5222-5226 (1991).
Trofatter et al., “A Novel Moesin-, Ezrin-, Radixin-like Gene Is a Candidate for the Neurofibromatosis 2 Tumor Suppressor”,Cell,72:791-800 (1993).
Paul et al., “characterization of fodrin interaction with the NF2 tumor suppressor gene product schwannomin (merlin) and varying strengths of protein binding that correlate with NF2 patient phenotypes.”Neurology,48(3) (suppl.2):A393-A394 (1997).
Scoles et al., “The neurofibromatosis 2 gene product schwannomin interacts with beta-II-spectrin.”Am. J. of Human Genetics,59(4 suppl.)Abstract A5 (1996).
Scoles et al., “Identification and characterization of interaction between the NF2 geneproduct Schwannomin and beta-II-spectrin.”Mol. Biol. of the Cell,7(suppl.):386A (1996).
Takeshima et al., “Detection of cellular proteins taht interact with the NF2 tumor suppressor gene.”Oncogene,9(8):2135-2144 (1994).
Asano, K. et al., “Conservation and Diversity of Eukaryotic Translation Initiation Factor elF3”,J. Bio. Chem.,272(2): 1101-1109 (1997).
Pulst Stefan M.
Scoles Daniel R.
Campbell & Flores LLP
Cedars-Sinai Medical Center
Myers Carla J.
LandOfFree
Nucleic acid encoding Schwannomin-Binding-Proteins and... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Nucleic acid encoding Schwannomin-Binding-Proteins and..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Nucleic acid encoding Schwannomin-Binding-Proteins and... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2894119