Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Reexamination Certificate
2001-05-22
2004-06-29
Swartz, Rodney P (Department: 1645)
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
C424S093200, C424S185100, C424S192100, C435S041000, C435S069100, C530S300000, C536S023100, C536S023500
Reexamination Certificate
active
06756478
ABSTRACT:
FIELD OF THE INVENTION
The present invention contemplates compositions related to genes found in lymphocytes, e.g., cells which function in the immune system. These genes are useful markers, and may function in controlling development, differentiation, and/or physiology of the mammalian immune system. In particular, the application provides nucleic acids, proteins, antibodies, and methods of using them.
BACKGROUND OF THE INVENTION
The circulating component of the mammalian circulatory system comprises various cell types, including red and white blood cells of the erythroid and myeloid cell lineages. See, e.g., Rapaport (1987)
Introduction to Hematology
(2d ed.) Lippincott, Philadelphia, Pa.; Jandl (1987)
Blood: Textbook of Hematology,
Little, Brown and Co., Boston, Mass.; and Paul (ed.) (1993)
Fundamental Immunology
(3d ed.) Raven Press, N.Y.
Dendritic cells (DC) are antigen-processing or presenting cells, and are found in all tissues of the body. See Steinman (1991)
Annual Review of Immunology
9:271-296; and Banchereau and Schmitt (eds. 1994)
Dendritic Cells in Fundamental and Clinical Immunology
Plenum Press, NY. These DC can be classified into various categories, including: interstitial dendritic cells of the heart, kidney, gut, and lung; Langerhans cells in the skin and mucous membranes; interdigitating dendritic cells in the thymic medula and secondary lymphoid tissue; and blood and lymph dendritic cells. Although dendritic cells in each of these compartments are CD45+ leukocytes that apparently arise from bone marrow, they may exhibit differences that relate to maturation state and microenvironment.
These dendritic cells efficiently process and present antigens to, e.g., T cells. They stimulate responses from naive and memory T cells in the paracortical area of secondary lymphoid organs. There is some evidence for a role in induction of tolerance.
The primary and secondary B-cell follicles contain follicular dendritic cells that trap and retain intact antigen as immune complexes for long periods of time. These dendritic cells present native antigen to B cells and are likely to be involved in the affinity maturation of antibodies, the generation of immune memory, and the maintenance of humoral immune responses.
Monocytes are phagocytic cells that belong to the mononuclear phagocyte system and reside in the circulation. See Roitt (ed)
Encyclopedia of Immunology
Academic Press, San Diego. These cells originate in the bone marrow and remain only a short time in the marrow compartment once they differentiate. They then enter the circulation and can remain there for a relatively long period of time, e.g., a few days. The monocytes can enter the tissues and body cavities by the process designated diapedesis, where they differentiate into macrophages and possibly into dendritic cells. In an inflammatory response, the number of monocytes in the circulation may double, and many of the increased number of monocytes diapedese to the site of inflammation.
Antigen presentation refers to the cellular events in which a proteinaceous antigen is taken up, processed by antigen presenting cells (APC), and then recognized to initiate an immune response. The most active antigen presenting cells have been characterized as the macrophages, which are direct developmental products from monocytes; dendritic cells; and certain B cells.
Macrophages are found in most tissues and are highly active in internalization of a wide variety of protein antigens and microorganisms. They have a highly developed endocytic activity, and secrete many products important in the initiation of an immune response. For this reason, it is believed that many genes expressed by monocytes or induced by monocyte activation are likely to be important in antigen uptake, processing, presentation, or regulation of the resulting immune response.
However, dendritic cells and monocytes are poorly characterized, both in terms of proteins they express, and many of their functions and mechanisms of action, including their activated states. In particular, the processes and mechanisms related to the initiation of an immune response, including antigen pocessing and presentation, remain unclear. The absence of knowledge about the structural, biological, and physiological properties of these cells limits their understanding. Thus, medical conditions where regulation, development, or physiology of antigen presenting cells is unusual remain unmanageable.
SUMMARY OF THE INVENTION
The present invention is based, in part, upon the discovery of various mammalian Dendritic Cell Membrane Protein (DCMP) genes, exemplified by the specific DCMP1 and DCMP2 embodiments. Distribution data indicates a broader cellular distribution, and structural data suggests some function. The DCMP1 exhibits similarity to a class of lectins and asialoglycoprotein receptors. The DCMP2 embodiments described exhibit significant sequence similarity to a macrophage cell asialoglycoprotein receptor. The invention embraces agonists and antagonists of the gene products, e.g., mutations (muteins) of the natural sequences, fusion proteins, chemical mimetics, antibodies, and other structural or functional analogs. It is also directed to isolated genes encoding proteins of the invention. Various uses of these different protein or nucleic acid composition are also provided.
In particular embodiments, the invention provides a binding compound comprising an antibody binding site which specifically binds to a DCMP1 protein; or a polypeptide selected from: Gly Val Ser Glu Leu Gln Glu His Thr Thr Gln Lys Ala His Leu Gly His Cys Pro His Cys Pro Ser Val Cys Val Pro (residues 118-144 of SEQ ID NO: 4); Gln Val Ala Thr Leu Asn Asn Asn Ala Ser Thr Glu Gly Thr Cys Cys (residues 166-181 of SEQ ID NO: 4); or Trp Lys Pro Gly Gln Pro Asp Asn Trp Gln Gly His Gly Leu Gly (residues 263-277 of SEQ ID NO: 4). In preferred embodiments, in the binding compound, the antibody binding site is: specifically immunoreactive with a protein of SEQ ID NO: 2 or 8; specifically immunoreactive with a protein of residues 118 to 144 of SEQ ID NO: 4; raised against a purified or recombinantly produced human DCMP1 protein; raised against a purified or recombinantly produced human protein comprising sequence of residues 118 to 144 of SEQ ID NO: 4; in a monoclonal antibody, Fab, or F(ab)2; or the binding compound is: detectably labeled; sterile; or in a buffered composition.
The invention embraces methods using those binding compounds, comprising contacting the binding compound with a biological sample comprising an antigen to form a binding compound:antigen complex. In certain embodiments, the biological sample is human, and the binding compound is an antibody. The invention also provides a detection kit comprising such binding compound and: instructional material for the use of such binding compound for the detection; or a compartment providing segregation of the binding compound.
The invention also provides a substantially pure or isolated polypeptide, which specifically binds to such binding compounds. In various embodiments, the polypeptide: comprises at least a fragment of at least 14 amino acid residues from a primate DCMP1 protein; comprises at least 14 amino acids of residues 118 to 144 of SEQ ID NO: 4; is a soluble polypeptide; is detectably labeled; is in a sterile composition; is in a buffered composition; binds to an sialic acid residue; is recombinantly produced, or has a naturally occurring polypeptide sequence.
Nucleic acid embodiments are provided, including a nucleic acid encoding a polypeptide above, when purified. Often, the nucleic acid: comprises at least 30 nucleotides of the coding portion of SEQ ID NO: 1 or 7; comprises at least 30 nucleotides from nucleotides 608-688 of SEQ ID NO: 3; or comprises at least 30 nucleotides from nucleotides 752-799 of SEQ ID NO: 3, or it may comprise an insert which selectively hybridizes to a nucleic acid encoding a polypeptide defined above. The invention also provides a cell transfected with such a nucleic acid, e.g., which consists of the protei
Bates Elizabeth Esther Mary
Ford John
Lebecque Serge J. E.
Ravel Odile
Saeland Sem
Biro Michael G.
Schering Corporation
Swartz Rodney P
Thampoe Immac J.
Triolo Thomas A.
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