Chemistry: molecular biology and microbiology – Micro-organism – per se ; compositions thereof; proces of... – Bacteria or actinomycetales; media therefor
Reexamination Certificate
1999-03-08
2003-07-01
Kemmerer, Elizabeth (Department: 1647)
Chemistry: molecular biology and microbiology
Micro-organism, per se ; compositions thereof; proces of...
Bacteria or actinomycetales; media therefor
C435S320100, C435S325000, C536S023100, C536S023500
Reexamination Certificate
active
06586228
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to compositions and methods for affecting mammalian physiology, including morphogenesis or immune system function. In particular, it provides nucleic acids, proteins, and antibodies which regulate development and/or the immune system. Diagnostic and therapeutic uses of these materials are also disclosed.
BACKGROUND OF THE INVENTION
Recombinant DNA technology refers generally to techniques of integrating genetic information from a donor source into vectors for subsequent processing, such as through introduction into a host, whereby the transferred genetic information is copied and/or expressed in the new environment. Commonly, the genetic information exists in the form of complementary DNA (cDNA) derived from messenger RNA (mRNA) coding for a desired protein product. The carrier is frequently a plasmid having the capacity to incorporate cDNA for later replication in a host and, in some cases, actually to control expression of the cDNA and thereby direct synthesis of the encoded product in the host. See, e.g., Sambrook, et al. (1989)
Molecular Cloning: A Laboratory Manual
, (2d ed.), vols. 1-3, CSH Press, NY.
For some time, it has been known that the mammalian immune response is based on a series of complex cellular interactions, called the “immune network”. Recent research has provided new insights into the inner workings of this network. While it remains clear that much of the immune response does, in fact, revolve around the network-like interactions of lymphocytes, macrophages, granulocytes, and other cells, immunologists now generally hold the opinion that soluble proteins, known as lymphokines, cytokines, or monokines, play critical roles in controlling these cellular interactions. The interferons are generally considered to be members of the cytokine family. Thus, there is considerable interest in the isolation, characterization, and mechanisms of action of cell modulatory factors, an understanding of which will lead to significant advancements in the diagnosis and therapy of numerous medical abnormalities, e.g., immune system disorders.
Lymphokines apparently mediate cellular activities in a variety of ways. See, e.g., Paul (ed. 1996)
Fundamental Immunology
3d ed., Raven Press, New York; and Thomson (ed. 1994)
The Cytokine Handbook
2d ed., Academic Press, San Diego. They have been shown to support the proliferation, growth, and/or differentiation of pluripotential hematopoietic stem cells into vast numbers of progenitors comprising diverse cellular lineages which make up a complex immune system. Proper and balanced interactions between the cellular components are necessary for a healthy immune response. The different cellular lineages often respond in a different manner when lymphokines are administered in conjunction with other agents.
Cell lineages especially important to the immune response include two classes of lymphocytes: B-cells, which can produce and secrete immunoglobulins (proteins with the capability of recognizing and binding to foreign matter to effect its removal), and T-cells of various subsets that secrete lymphokines and induce or suppress the B-cells and various other cells (including other T-cells) making up the immune network. These lymphocytes interact with many other cell types.
One means to modulate the effect of a cytokine upon binding to its receptor, and therefore potentially useful in treating inappropriate immune responses, e.g., autoimmune, inflammation, sepsis, and cancer situations, is to inhibit the receptor signal transduction. Unfortunately, finding reagents capable of serving as an antagonist or agonist has been severely hampered by the failure to fully identify all of the components within the signaling systems. In order to characterize the structural properties of a cytokine receptor in greater detail and to understand the mechanism of action at the molecular level, purified receptor will be very useful. The receptors provided herein, by comparison to other receptors or by combining structural components, will provide further understanding of signal transduction induced by ligand binding.
The isolated receptor gene should provide means to generate an economical source of the receptor, allow expression of more receptors on a cell leading to increased assay sensitivity promote characterization of various receptor subtypes and variants, and allow correlation of activity with receptor structures. Moreover, fragments of the receptor may be useful as agonists or antagonists of ligand binding. See, e.g., Harada, et al. (1992)
J. Biol. Chem
. 267:22752-22758. Often, there are at least two critical subunits in the functional receptor. See, e.g., Gonda and D'Andrea (1997)
Blood
89:355-369; Presky, et al. (1996)
Proc. Nat'l Acad. Sci. USA
93:14002-14007; Drachman and Kaushansky (1995)
Curr. Opin. Hematol
. 2:22-28; Theze (1994)
Eur. Cytokine Netw
, 5:353-368; and Lemmon and Schlessinger (1994)
Trends Biochem. Sci
, 19:459-463.
From the foregoing, it is evident that the discovery and development of new soluble proteins and their receptors, including ones similar to lymphokines, should contribute to new therapies for a wide range of degenerative or abnormal conditions which directly or indirectly involve development, differentiation, or function, e.g., of the immune system and/or hematopoietic cells. In particular, the discovery and understanding of novel receptors for lymphokine-like molecules which enhance or potentiate the beneficial activities of other lymphokines would be highly advantageous. The present invention provides new receptors for ligands exhibiting similarity to cytokine like compositions and related compounds, and methods for their use.
SUMMARY OF THE INVENTION
The present invention is directed to novel receptors related to cytokine receptors, e.g., primate or rodent, cytokine receptor like molecular structures, designated DNAX Interferon-like Receptor Subunits (DIRS), and their biological activities. In particular, it provides description of two different subunits, designated DIRS1 and DIRS2. It includes nucleic acids coding for the polypeptides themselves and methods for their production and use. The nucleic acids of the invention are characterized, in part, by their homology to cloned complementary DNA (cDNA) sequences enclosed herein.
The present invention provides, in polypeptide embodiments: a substantially pure or recombinant DIRS1 polypeptide comprising at least three distinct nonoverlapping segments of at least four amino acids identical to segments of SEQ ID NO: 2; a substantially pure or recombinant DIRS1 polypeptide comprising at least two distinct nonoverlapping segments of at least five amino acids identical to segments of SEQ ID NO: 2; a natural sequence DIRS1 comprising mature SEQ ID NO: 2; a fusion polypeptide comprising DIRS1 sequence; a substantially pure or recombinant DIRS2 polypeptide comprising at least three distinct nonoverlapping segments of at least ten amino acids identical to segments of SEQ ID NO: 4; a substantially pure or recombinant DIRS2 polypeptide comprising at least two distinct nonoverlapping segments of at least eleven amino acids identical to segments of SEQ ID NO: 4; a natural sequence DIRS2 comprising SEQ ID NO: 4; or a fusion polypeptide comprising DIRS2 sequence. Preferred embodiments include, e.g., the substantially pure or isolated antigenic: DIRS1 polypeptide, wherein the distinct nonoverlapping segments of identity: include one of at least eight amino acids; include one of at least four amino acids and a second of at least five amino acids; include at least three segments of at least four, five, and six amino acids, or include one of at least twelve amino acids; or DIRS2 polypeptide, wherein the distinct nonoverlapping segments of identity: include one of at least thirteen amino acids; include one of at least eleven amino acids and a second of at least thirteen amino acids; include at least three segments of at least ten, eleven, and twelve amino acids; or include one of at least twenty-five amino acids. Ot
Moore Kevin W.
Murgolo Nicholas J.
Parham Christi L.
Brody Tom
Ching Edwin P.
Kemmerer Elizabeth
Schering Corporation
Wegert Sandra
LandOfFree
Polynucleotides encoding DIRS1 does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Polynucleotides encoding DIRS1, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Polynucleotides encoding DIRS1 will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3040953