Human FGF-21 nucleic acids

Details Human FGF-21 nucleic acids Human FGF-21 nucleic acids

2000-11-16

2004-04-06

Eyler, Yvonne (Department: 1646)

Chemistry: molecular biology and microbiology

Animal cell, per se ; composition thereof; process of...

C435S252300, C435S254110, C435S254200, C435S320100, C435S069100, C536S023100, C536S023500, C536S024300, C530S350000

Reexamination Certificate

active

06716626

ABSTRACT:

TECHNICAL FIELD
The present invention relates to nucleic acid sequences encoding a member of the fibroblast growth factor (FGF) family, and to polypeptides encoded by the nucleic acid sequence.
BACKGROUND OF THE INVENTION
The prototypic fibroblast growth factors (FGFs), FGF-1 and FGF-2, were originally isolated from brain and pituitary as mitogens for fibroblasts. However, FGF-1 and FGF-2 are widely expressed in developing and adult tissues, and are polypeptides with multiple biological activities including angiogenesis, mitogenesis, cellular differentiation and repair of tissue injury (Baird, A. et al.,
Cancer Cells
3:239-243 (1991); Burgess, W. H. et al.,
Annu. Rev. Biochem.
58:575-606 (1989). According to the published literature, the FGF family now consists of at least nineteen members, FGF-1 to FGF-19. FGF-3 was identified to be a common target for activation by the mouse mammary tumor virus (Dickson et al.,
Ann. N.Y. Acad. Sci.
638:18-26 (1991); FGF-4 to FGF-6 were identified as oncogene products (Yoshida et al.,
Ann. NY Acad. Sci.
638:27-37 (1991); Goldfarb et al.,
Ann. NY Acad. Sci
638:38-52 (1991); Coulier et al.,
Ann. NY Acad. Sci.
638:53-61 (1991)). FGF-10 was identified from rat lung by homology-based polymerase chain reaction (PCR) (Yamasaki et al.,
J. Biol. Chem.
271:15918-15921 (1996)). FGF-11 to FGF-14 (FGF homologous factors (FHFs) 1 to 4) were identified from human retina by a combination of random cDNA sequencing, data base searches and homology-based PCR (Smallwood et al.,
Proc. Natl. Acad. Sci. USA
93:9850-9857 (1996)). FGF-15 was identified as a downstream target of a chimeric homeodomain oncoprotein (McWhirter et al.,
Development
124:3221-3232 (1997)). FGF-16, FGF-17, and FGF-18 were identified from rat heart and embryos by homology-based PCR, respectively (Miyake et al.,
Biochem. Biophys. Res. Commun.
243:148-152 (1998); Hoshikawa et al.,
Biochem. Biophys. Res. Commun.
244:187-191 (1998); Ohbayashi et al.,
J. Biol. Chem.
273:18161-18164 (1998)). Recently, FGF-19 was identified from human fetal brain by data base search (Nishimura et al.,
Biochim. Biophys. Acta
1444:148-151 (1999)). They have a conserved ~120-amino acid residue core with ~30 to 60% amino acid identity. These FGFs also appear to play important roles in both developing and adult tissues. Thus, there is a need in the art for additional FGF molecules having functions and activities that differ from the known FGFs and for FGF molecules specifically expressed in tissues implicated in human disease.
SUMMARY OF THE INVENTION
The present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising at least eight contiguous nucleotides of SEQ ID NO:1 or 3;
(b) a polynucleotide having at least 80% homology to the polynucleotide of (a); and
(c) a polynucleotide encoding a protein expressed by a polynucleotide having the sequence of SEQ ID NO:1 or 3.
The invention further provides for the use of the isolated polynucleotides or fragments thereof as diagnostic probes or as primers.
The present invention also provides a composition comprising a polypeptide, wherein said polypeptide is selected from the group consisting of:
(a) a polypeptide comprising at least 6 contiguous amino acids encoded by SEQ ID NO:1 or 3;
(b) a polypeptide encoded by a polynucleotide comprising SEQ ID NO:1 or 3; and
(c) a variant of the polypeptide of SEQ ID NO:2 or 4.
In certain preferred embodiments of the invention, the polynucleotide is operably linked to an expression control sequence. The invention further provides a host cell, including bacterial, yeast, insect and mammalian cells, transformed with the polynucleotide sequence. The invention also provides full-length cDNA and full-length polynucleotides corresponding to SEQ ID NO:1 or 3.
Protein and polypeptide compositions of the invention may further comprise a pharmaceutically acceptable carrier. Compositions comprising an antibody that specifically reacts with such protein or polypeptide are also provided by the present invention.
The invention also provides for the production of large amounts of otherwise minor cell populations of cells to be used for generation of cDNA libraries for the isolation of rare molecules expressed in the precursors cells or progeny; cells produced by treatment may directly express growth factors or other molecules, and conditioned media is screened in assays for novel activities.
The invention further provides for the isolation, self-renewal and survival of mammalian stem cells and the differentiation of their progeny.
The invention also provides for compositions and methods of preventing or slowing the degeneration of or increasing the numbers of hepatic cells, in disease states including but not limited to, cirrhosis of the liver, hepatitis, and post-surgical and post-injury tissue regeneration; of preventing or slowing degeneration of or increasing the numbers of cells in the testes in disease states such as infertility and impotence, and of preventing or slowing degeneration of or increasing the numbers of cells of the thymus in disorders of the thymus and immune system.
The invention also provides for compositions and methods for identifying inhibitors of FGF-21 function, useful in disease states such as liver and testicular cancers, or leukemias, lymphomas or other cancers, and proliferative or differentiation disorders of cells derived from the thymus.


REFERENCES:
patent: 5766883 (1998-06-01), Ballance et al.
patent: 5876969 (1999-03-01), Fleer et al.
patent: WO 97/24445 (1997-07-01), None
patent: WO 97/25345 (1997-07-01), None
patent: WO 99/27100 (1999-03-01), None
patent: WO 00/54813 (2000-09-01), None
patent: WO 00/60085 (2000-10-01), None
patent: WO 01/07595 (2001-02-01), None
patent: WO 01/18209 (2001-03-01), None
patent: WO 01/18210 (2001-03-01), None
Smallwood et al, Fibroblast growth factor (FGF) homologous factors: New members of the FGF family implicated in nervous system development. Proc. Natl. Acad. Sci. USA 93:9850-9857, 1996.*
Mahairas, et al. EMBL database Accession NO: AQ175436, Oct. 17, 1998.*
Database EMBL, Accession No. AV050323, Jun. 22, 1999.
Database EMBL, Accession No. AB006136, Jul. 20, 2000.
Nishimura et al., “Identification of a Novel FGF, FGF-21, Preferentially Expressed in the Liver,”Biochim. Biophys. Acta 1492(1):203-206, Jun. 21, 2000.
Baird and Klagsbrun, “The Fibroblast Growth Factor Family,”Cancer Cells 3(6): 239-243, Jun. 1991.
Belluardo et al., “Comparative Localization of Fibroblast Growth Factor Receptor-1, -2, and -3 mRNAs in the Rat Brain: In Situ Hybridization Analysis,”The Journal of Comparative Neurology 379: 226-246, 1997.
Burgess and Maciag, “The Heparin-Binding (Fibroblast) Growth Factor Family of Proteins,”Annu. Rev.Biochem. 58: 575-606, 1989.
Coulier et al., “TheFGF6Gene within theFGFMultigene Family,”Annals of the New York Academy of Sciences 638:53-61, 1991.
Crossley and Martin, “The mouseFgf8gene encodes a family of polypeptides and is expressed in regions that direct outgrowth and patterning in the developing embryo,”Development 121: 439-451, 1995.
Dickson et al., “Expression, Processing, and Properties of int-2,”Annals of the New York Academy of Sciences 638: 18-26, 1991.
Gemel et al., “Structure and Sequence of HumanFGF8, ”Genomics 35: 253-257, 1996.
Ghosh et al., “Molecular Cloning and Characterization of HumanFGF8Alternative Messenger RNA Forms,”Cell Growth&Differentiation 7: 1425-1434, Oct. 1996.
Goldfarb et al., “Expression and Possible Functions of the FGF-5 Gene,”Annals of the New York Academy of Sciences 638: 38-52, 1991.
Gospodarowicz and Cheng, “Heparin Protects Basic and Acidic FGF From Inactivation,”Journal of Cellular Physiology 128: 475-484, 1986.
Hoshikawa et al., “Structure and Expression of a Novel Fibroblast Growth Factor, FGF-17, Preferentially Expressed in the Embryonic Brain,”Biochemical and Biophysical Research Communications 244: 187-191, 1998.
Lopez et al., “Basic Fibroblast Growth Factor in a Porcine Model of Chronic Myocardial Ischemia: A Compariso

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