Polynucleotides encoding human Hox C10

Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...

Reexamination Certificate

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C435S091400, C435S320100, C435S070100, C435S325000, C435S243000, C536S023100, C536S023500

Reexamination Certificate

active

06358702

ABSTRACT:

This invention relates to newly identified polynucleotides, polypeptides encoded by such polynucleotides, the use of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides. More particularly, the polypeptides of the present invention are human Hox C10 polypeptides. The invention also relates to identifying mesenchymal stem cells (MSCs) or other cells comprising such polypeptides or polynucleotides that encode the polypeptides.
The Hox family of transcription factors exhibit a wide variety of functions and may control the organization of the embryo along an anterior-posterior axis. Thus, the structure (e.g., limb) and organ (e.g., kidney) that develops in the embryo is strongly influenced by which Hox gene is expressed temporally and spatially in that region. In addition, Hox genes may play important lineage-specific roles in a number of mature tissues. The fact that the Hox genes determine pattern formation in embryos suggests that Hox genes perform important functions in pluripotent stem cell populations.
The expression of a Hox family gene, HoxB4, has been implicated as being important in controlling hematopoietic stem cell (HSC) proliferation.
Mesenchymal stem cells are the formative pluripotential cells found inter alia in bone marrow, blood, dermis and periosteum that are capable of differentiating into any of the specific types of mesenchymal or connective tissues (i.e. the tissues of the body that support the specialized elements; particularly adipose, osseous, cartilaginous, elastic, and fibrous connective tissues) depending upon various influences polypeptides growth from bioactive factors, such as polypeptide growth factors.
In accordance with one aspect of the present invention, there are provided novel polypeptides that are produced by MSCs as well as biologically active and diagnostically or therapeutically useful fragments, analogs and derivatives thereof.
In accordance with another aspect of the present invention, there are provided isolated nucleic acid molecules encoding such polypeptides, including precursor RNA, mRNAs, cDNAs, genomic DNA as well as biologically active and diagnostically or therapeutically useful fragments, analogs and derivatives thereof.
In accordance with another aspect of the present invention there is provided an isolated nucleic acid molecule encoding a mature polypeptide expressed by the DNA contained in material deposited with the ATCC on Oct. 2, 1997 and which has ATCC Deposit No. 209323.
In accordance with another aspect of the present invention there are provided nucleic acid probes comprising nucleic acid molecules of sufficient length to specifically hybridize to sequences of the present invention.
In accordance with yet a further aspect of the present invention, there is provided a process for producing such polypeptides by recombinant techniques which comprises culturing recombinant prokaryotic and/or eukaryotic host cells, containing a nucleic acid sequence of the present invention, under conditions promoting expression of said protein and subsequent recovery of said protein.
In accordance with yet a further aspect of the present invention, there is provided a process for utilizing such polypeptides, or polynucleotides encoding such polypeptides for identifying human MSCs by utilizing the polynucleotides as probes or by expressing the polypeptides encoded thereby, using such polypeptides to produce an antibody specific for one of the polypeptides and then utilizing the antibody to identify the MSCs. Further such polynucleotides, polypeptides and antibodies may be utilized to aid in the identification of MSCs from other species, as well as to investigate/identify MSC functions in humans or other species.
In accordance with yet a further aspect of the present invention, there are provided antibodies against such polypeptides and a method of employing such antibodies to detect diseases related to an overexpression or under expression of the polypeptide of the present invention.
In accordance with another aspect of the present invention there is provided a method of diagnosing a disease or a susceptibility to a disease related to a mutation in the nucleic acid sequences and the proteins encoded by such nucleic acid sequences.
In accordance with yet a further aspect of the present invention, there is provided a process for utilizing such polypeptides, or polynucleotides encoding such polypeptides, for in vitro purposes related to scientific research, synthesis of DNA and manufacture of DNA vectors.
These and other aspects of the present invention should be apparent to those skilled in the art from the teachings herein.


REFERENCES:
Adams, M., et al., “Homo sapiens cDNA 5′ end similar to homeobox Hox-C10,” Database EMEST17, E.M.B.L. Databases, Accession Nos. AA314165 & AA307551 (Apr. 18, 1997).
Cannizaro, et al., “Human Homeo Box-containing Genes Located at Chromosome Regions 2q31—2q37 and 12q12—12q13,”Am J Hum Genet,41(1):1-15 (1987).
Flagiello, D., et al., “Distinct patterns of all-trans retinoic acid dependent expression of HOXB and HOXC homeogenes in human embryonal and small-cell lung carcinoma cell lines,”Febs Lett.,415:263-267 (1997).
Peterson, Ron L., “Isolation and Characterization of four Abdominal-B-Related Hox Genes Contained in the 5′Region of the murine Hoxc cluster,” Citations from Dissertation Abstracts:DIS, 55-05B:1738-1878 (1994).
Pollack, et al., “Gain of function mutations for paralogous Hox genes: Implications for the evolution of Hox gene function,”Proc Natl Acad Sci USA,92:4492-4496 (1995).
Sharkey, M., et al., “Hox genes in evolution: protein surfaces and paralog groups,”Trends in Genetics,13(4):145-151 (1997).

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