Dendritic enriched secreted lymphocyte activation molecule

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues

Reexamination Certificate

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C536S023500, C435S069100, C435S071100, C435S320100, C435S471000

Reexamination Certificate

active

06620912

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to a novel human gene encoding a polypeptide which is a member of the Secreted Lymphocyte Activation Molecule (SLAM) family. More specifically, the present invention relates to a polynucleotide encoding a novel human polypeptide named Dendritic Enriched Secreted Lymphocyte Activation Molecule, or “D-SLAM.” This invention also relates to D-SLAM polypeptides, as well as vectors, host cells, antibodies directed to D-SLAM polypeptides, and the recombinant methods for producing the same. Also provided are diagnostic methods for detecting disorders related to the immune system, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying agonists and antagonists of D-SLAM activity.
BACKGROUND OF THE INVENTION
A member of the immunoglobulin gene superfamily, SLAM is rapidly induced after activation of naive T- and B-cells. (Cocks, B. G., “A Novel Receptor Involved in T-Cell Activation,” Nature 376:260-263 (1995); Aversa, G., “Engagement of the Signaling Lymphocytic Activation Molecule (SLAM) on Activated T Cells Results in Il-2-Independent, Cyclosporin A-Sensitive T Cell Proliferation and IFN-&ggr; Production,” J. Immun. 4036-4044 (1997).) A multifunctional 70 kDa glycoprotein, SLAM causes proliferation and differentiation of immune cells. (Punnonen, J., “Soluble and Membrane-bound Forms of Signaling Lymphocytic Activation Molecule (SLAM) Induce Proliferation and Ig Synthesis by Activated Human B Lymphocytes,” J. Exp. Med. 185:993-1004 (1997).) To elicit an immune response, both a secreted form of SLAM, as well as a membrane bounded SLAM, are thought to interact.
It is also known that dendritic cells (DC) are the principal antigen presenting cells involved in primary immune responses; their major function is to obtain antigen in tissues, migrate to lymphoid organs, and activate T cells. (Mohamadzadeh, M. et al., J. Immunol. 156:3102-3106 (1996).) In fact, DC are usually the first immune cells to arrive at sites of inflammation on mucous membranes. (See, e.g., Weissman, D. et al., J. Immunol. 155:4111-4117 (1995).) There is a constant need to identify new polypeptide factors which may mediate interactions between DC and T cells, leading to the activation and/or proliferation of immune cells. To date, however, SLAM molecules have not been identified on DC cells.
Thus, there is a need for polypeptides that affect the proliferation, activation, survival, and/or differentiation of immune cells, such as T- and B-cells, since disturbances of such regulation may be involved in disorders relating to immune system. Therefore, there is a need for identification and characterization of such human polypeptides which can play a role in detecting, preventing, ameliorating or correcting such disorders.
SUMMARY OF THE INVENTION
The present invention relates to a novel polynucleotide and the encoded polypeptide of D-SLAM. Moreover, the present invention relates to vectors, host cells, antibodies, and recombinant methods for producing the polypeptides and polynucleotides. Also provided are diagnostic methods for detecting disorders relates to the polypeptides, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying binding partners of D-SLAM.


REFERENCES:
patent: 5576423 (1996-11-01), Aversa et al.
patent: WO 94/01548 (1994-01-01), None
patent: WO 99/40184 (1999-08-01), None
patent: WO 00/18800 (2000-04-01), None
Kingsbury, Gillian et al., “Cloning, Expression, and Function of Blame, a Novel Member of the CD2 Family”, J. of Immunology, 166:5675-5680 (2001).
International Search Report, Application No. PCT/US00/21130, mailed Nov. 14, 2000.
Punnonen et al., “Soluble and Membrane-bound forms of signaling lymphocytic activation molecule (SLAM) induce proliferation and Ig synthesis by activated Human B lymphocytes,”J. Exp. Med.185(6):993-1004 (1997).
Ferrante et al., “Cytokine production and surface marker expression in acute and stable multiple sclerosis: altered IL-12 production and augmented signaling lymphocytic activation Molecule (SLAM)-expressing lymphocytes in acute multiple sclerosis,”J. Immunol.185(6):1514-1521 (1998).
Genbank Accession No. AF14235 (Jun. 1, 1999).
Genbank Accession No. N62522 (Mar. 1, 1996), Hillier et al.
Genbank Accession No. AA627522 (Oct. 31, 1997), Strausberg et al.
Genbank Accession No. R11635 (Apr. 11, 1995), Hillier et al.
Genbank Accession No. AA379112 (Apr. 21, 1997), Adams et al.
Genbank Accession No. R09841 (Apr. 6, 1995), Hillier et al.
Genbank Accession No. Z20320 (Feb. 7, 1995), MRC Human Genome Mapping Project.
Genbank Accession No. N79421 (Apr. 2, 1996), Hillier et al.
Genbank Accession No. D45800 (Feb. 20, 1995), Itoh et al.
Genbank Accession No. AA917335 (Jun. 24, 1998), Strausberg et al.
Genbank Accession No. AI094818 (Oct. 1, 1998), Strausberg et al.
Genbank Accession No. G22227 (May 31, 1996), Hudson.
Cocks et al. (1995) Nature 376:260-263.
Geneseq Accession No. Q76829 (1994), Gross et al.

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