Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
1997-11-25
2002-03-26
Saunders, David (Department: 1644)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C435S069100, C435S252330, C435S320100, C435S325000, C435S366000, C435S975000, C530S350000, C536S023500
Reexamination Certificate
active
06361939
ABSTRACT:
FIELD OF THE INVENTION
The present invention contemplates compositions related to genes found in dendritic cells, cells which function in the immune system. These genes function in controlling development, differentiation, and/or physiology of 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 are antigen-presenting cells, and are found in all tissues of the body. They 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 medulla 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.
Dendritic cells (DC), which are specialized antigen-presenting 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 being the affinity maturation of antibodies, the generation of immune memory, and the maintenance of humoral immune responses.
However, dendritic cells are poorly characterized, both in terms of proteins they express, and many of their functions and mechanisms of action. 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 dendritic cells is unusual remain unmanageable.
SUMMARY OF THE INVENTION
The present invention is based, in part, upon the discovery of three clones isolated from activated dendritic cells, which identify mammalian genes of structural and functional relationship. It embraces agonists and antagonists of these molecules designated A05F12 (diubiquitin), A07C03 (Ig family gene), and E02B02 (LAMP-like gene), 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.
The present invention provides a composition of matter selected from: a substantially pure or recombinant A05F12 protein or peptide exhibiting at least about 85% sequence identity over a length of at least about 12 amino acids to SEQ ID NO: 2 or 4; a natural sequence A05F12 comprising SEQ ID NO: 2 or 4; a fusion protein comprising A05F12 sequence; a substantially pure or recombinant A07C03 protein or peptide exhibiting at least about 85% sequence identity over a length of at least about 12 amino acids to SEQ ID NO: 6, 8, or 10; a natural sequence A07C03 comprising SEQ ID NO: 6, 8, or 10; a fusion protein comprising A07C03 sequence; a substantially pure or recombinant E02B02 protein or peptide exhibiting at least about 85% sequence identity over a length of at least about 12 amino acids to SEQ ID NO: 12; a natural sequence E02B02 comprising SEQ ID NO: 12; or a fusion protein comprising E02B02 sequence. In certain preferred embodiments, the substantially pure or isolated protein will comprise a segment exhibiting sequence identity to a corresponding portion of an: A05F12, wherein: the homology is at least about 90% identity and the portion is at least about 9 amino acids; the homology is at least about 80% identity and the portion is at least about 17 amino acids; or the homology is at least about 70% identity and the portion is at least about 25 amino acids; A07C03, wherein: the homology is at least about 90% identity and the portion is at least about 9 amino acids; the homology is at least about 80% identity and the portion is at least about 17 amino acids; or the homology is at least about 70% identity and the portion is at least about 25 amino acids; or E02B02, wherein: the homology is at least about 90% identity and the portion is at least about 9 amino acids; the homology is at least about 80% identity and the portion is at least about 17 amino acids; or the homology is at least about 70% identity and the portion is at least about 25 amino acids. Other preferred embodiments include where: A05F12 comprises a mature sequence of Table 1; the A05F12 protein or peptide: is from a warm blooded animal selected from a primate or rodent, such as a human or mouse; comprises at least one polypeptide segment of SEQ ID NO: 2 or 4; exhibits a plurality of portions exhibiting said identity; is a natural allelic variant of a primate or rodent A05F12; has a length at least about 30 amino acids; exhibits at least two non-overlapping epitopes which are specific for a primate or rodent A05F12; exhibits a sequence identity at least about 90% over a length of at least about 20 amino acids to a primate or rodent A05F12; has a molecular weight of at least 100 kD with natural glycosylation; is a synthetic polypeptide; is attached to a solid substrate; is conjugated to another chemical moiety; is a 5-fold or less substitution from natural sequence; or is a deletion or insertion variant from a natural sequence; A07C03 comprises a mature sequence of Table 2; the A07C03 protein or peptide: is from a warm blooded animal selected from a primate or rodent, such as a human or mouse; comprises at least one polypeptide segment of SEQ ID NO: 8 or 10; exhibits a plurality of portions exhibiting said identity; is a natural allelic variant of a primate or rodent A07C03; has a length at least about 30 amino acids; exhibits at least two non-overlapping epitopes which are specific for a primate or rodent A07C03; exhibits a sequence identity at least about 90% over a length of at least about 20 amino acids to a primate or rodent A07C03; has a molecular weight of at least 100 kD with natural glycosylation; is a synthetic polypeptide; is attached to a solid substrate; is conjugated to another chemical moiety; is a 5-fold or less substitution from natural sequence; or is a deletion or insertion variant from a natural sequence; E02B02 comprises a mature sequence of Table 3; or the E02B02 protein or peptide: is from a warm blooded animal selected from a primate, such as a human; comprises at least one polypeptide segment of SEQ ID NO: 12; exhibits a plurality of portions exhibiting said identity; is a natural allelic variant of a primate E02B02; has a length at least about 30 amino acids; exhibits at least two non-overlapping epitopes which are specific for a primate E02B02; exhibits a sequence identity at least about 90% over a length of at least about 20 amino acids to a primate E02B02; has a molecular weight of at least 100 kD with natural glycosylation; is a synthetic polypeptide; is attached to a solid substrate; is conjugated to another chemical moiety; is a 5-fold or less substitution from natural sequence; or is a deletion or insertion variant from a natural sequence. Other preferred embodiments include a composition comprising: a sterile A05F12 protein or peptide; the A05F12 protein or peptide and a carrier, wherein the carrier is: an aqueous compound, including water, saline, and/or buffer; and/or formulated for oral,
Banchereau Jacques
Bates Elizabeth Esther Mary
Caux Christophe
de Saint-Vis Blandine Marie
Lebecque Serge J. E.
Ching Edwin P.
McLaughlin Jaye P.
Saunders David
Schering Corporation
Tung Mary Beth
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