Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2003-06-12
2004-11-16
Brusca, John (Department: 1631)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C435S006120, C536S024100, C530S300000, C530S350000
Reexamination Certificate
active
06818754
ABSTRACT:
The Sequence Listing of this application is contained on a compact disc, which bears the file name “HYS-23DVBSequenceListing.txt”, 65,536 bytes in size, and was created on Jun. 12, 2003, and which is incorporated herein by reference in its entirety
BACKGROUND
2.1 Technical Field
The present invention provides novel polynucleotides and proteins encoded by such polynucleotides, along with uses for these polynucleotides and proteins, for example in therapeutic, diagnostic and research methods. In particular, the invention relates to a novel semaphorin-like polypeptide.
2.2 Background Art
Identified polynucleotide and polypeptide sequences have numerous applications in, for example, diagnostics, forensics, gene mapping; identification of mutations responsible for genetic disorders or other traits, to assess biodiversity, and to produce many other types of data and products dependent on DNA and amino acid sequences. Proteins are known to have biological activity, for example, by virtue of their secreted nature in the case of leader sequence cloning, by virtue of their cell or tissue source in the case of PCR-based techniques, or by virtue of structural similarity to other genes of known biological activity. It is to these polypeptides and the polynucleotides encoding them that the present invention is directed. In particular, this invention is directed to novel soluble semaphorin-like polypeptides and polynucleotides.
In the developing nervous system, growing axons are targeted to their correct targets by different mechanisms. Among these mechanisms are soluble and contact-mediated chemoattraction and chemrepulsion (Goodman (1996) Annu. Rev. Neurosci. 19, 341-377). Semaphorins, netrins, and ephrins family members have been identified as molecular cues for axonal guidance during development (Kikuchi et al (1999) Mol. Cell. Neurosci. 13, 9-23). Semaphorins are secreted and transmembrane proteins containing a characteristic domain of about 500 amino acids in their extracellular domain (sema domain). In contrast to the extracellular region, no common domain structures have been mapped to the cytoplasmic domains of semaphorins. However, many proline residues are found in the cytoplasmic domain and they may serve as a binding module for src homology 3 (SH3) containing proteins (Kikuchi et al (1999) Mol. Cell. Neurosci. 13, 9-23). Semaphorins are found in all eukaryotes from worm to mammals and some viruses, and are grouped into six classes based on the sema domain homology.
Sema III has been shown to be chemorepellent to sympathetic, sensory and spinal motor axons. Sema I has also been shown to be a contact-mediated chemorepellent in
Drosophila
for motor axons, and as a chemoattractant for sensory axons in grasshopper.
Semaphorin class VI family members are comprised of sema Y, rat sema Y and sema Z, mouse sema VIa and sema VIb. Sema Y mRNA is expressed in rat embryos but the levels decrease after birth. In the embryo, sema Y expression was initially seen in the dorsal spinal cord and the dermamyotome. By embryonic day 13 (E13) sema Y expression is highest in the ventral horn, dorsal root ganglia (DRG), dermatome, myotome, notochord, motor nuclei of cranial nerves, and throughout the brain surface including the marginal zone of the developing neocortex, thalamus, cerebellum and retina. Sema Y is also expressed in the granule cell progenitors, immature muscle and dermis. In adult tissues, sema Y is expressed in skeletal muscle, brain, and all areas of central nervous system examined. Thus, semaphorins may play a crucial role in development of nervous system.
Recently, plexins, which contain a distantly related sema domain, and neuropilins have been characterized as semaphorin receptors.
Although regulating aspects of neural development, semaphorins are also expressed in the immune system. In fact, while many semaphorins including sema Y have been shown to exhibit inhibitory growth cone collapsing activity and sema3A have been shown to attract cortical apical dendrites, sema4D (CD100) has been shown to modulate T and B lymphocyte function. Also, the virally encoded semaphorins are secreted by the infected cells and postulated to interfere with the host immune response.
Semaphorins and semaphorin receptors are crucial for the normal development and regulation of the nervous system. These are the molecular cues that guide the axons and neurons. The semaphorins and their receptors could be very useful in modulating neuronal growth regenerative capacity (such as in the case of spinal cord damage), treating neurodegenerative diseases, diagnosing and mapping genetic neuronal defects. They may be helpful in treating immunological disorders arising from T and B lymphocyte dysfunction, or treating viral infections and cancers.
SUMMARY OF THE INVENTION
This invention is based on the discovery of novel semaphorin-like polypeptides, novel isolated polynucleotides encoding such polypeptides, including recombinant DNA molecules, cloned genes or degenerate variants thereof, especially naturally occurring variants such as allelic variants, antisense polynucleotide molecules, and antibodies that specifically recognize one or more epitopes present on such polypeptides, as well as hybridomas producing such antibodies. Specifically, the polynucleotides of the present invention are based on a semaphorin-like polynucleotide isolated from a cDNA library prepared from fetal liver-spleen (Hyseq clone identification numbers 5688868 (SEQ ID NO: 1).
The compositions of the present invention additionally include vectors such as expression vectors containing the polynucleotides of the invention, cells genetically engineered to contain such polynucleotides and cells genetically engineered to express such polynucleotides.
The compositions of the invention provide isolated polynucleotides that include, but are not limited to, a polynucleotide comprising the nucleotide sequence set forth in the SEQ ID NO: 1-3, 5 or 12; or a fragment of SEQ ID NO: 1-3, 5 or 12; a polynucleotide comprising the full length protein coding sequence of the SEQ ID NO: 1-3, 5 or 12 (for example, SEQ ID NO: 4); and a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of any of SEQ ID NO: 1-3, 5 or 12. The polynucleotides of the present invention also include, but are not limited to, a polynucleotide that hybridizes under stringent hybridization conditions to (a) the complement of any of the nucleotide sequences set forth in SEQ ID NO: 1-3, 5 or 12; (b) a nucleotide sequence encoding any of SEQ ID NO: 4, 6-8, 11 or 13; a polynucleotide which is an allelic variant of any polynucleotides recited above having at least 70% polynucleotide sequence identity to the polynucleotides; a polynucleotide which encodes a species homolog (e.g. orthologs) of any of the peptides recited above; or a polynucleotide that encodes a polypeptide comprising a specific domain or truncation of the polypeptide comprising SEQ ID NO: 4.
A collection as used in this application can be a collection of only one polynucleotide. The collection of sequence information or unique identifying information of each sequence can be provided on a nucleic acid array. In one embodiment, segments of sequence information are provided on a nucleic acid array to detect the polynucleotide that contains the segment. The array can be designed to detect full-match or mismatch to the polynucleotide that contains the segment. The collection can also be provided in a computer-readable format.
This invention further provides cloning or expression vectors comprising at least a fragment of the polynucleotides set forth above and host cells or organisms transformed with these expression vectors. Useful vectors include plasmids, cosmids, lambda phage derivatives, phagemids, and the like, that are well known in the art. Accordingly, the invention also provides a vector including a polynucleotide of the invention and a host cell containing the polynucleotide. In general, the vector contains an origin of replication functional in at least one organism, convenient restricti
Arterburn Matthew C.
Boyle Bryan J.
Drmanac Radoje T.
Liu Chenghua
Mize Nancy K.
Brusca John
Nuvelo. Inc.
Polizotto Renée S.
Zhou Shubo (Joe)
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