Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 25 or more amino acid residues in defined sequence
Reexamination Certificate
1998-05-01
2001-08-07
Kemmerer, Elizabeth (Department: 1647)
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
25 or more amino acid residues in defined sequence
C530S326000, C530S300000, C530S350000
Reexamination Certificate
active
06271343
ABSTRACT:
BACKGROUND OF THE INVENTION
Proliferation and differentiation of cells of multicellular organisms are controlled by hormones and polypeptide growth factors. These diffusable molecules allow cells to communicate with each other and act in concert to form cells and organs, and to repair and regenerate damaged tissue. Examples of hormones and growth factors include the steroid hormones (e.g. estrogen, testosterone), parathyroid hormone, follicle stimulating hormone, the interleukins, platelet derived growth factor (PDGF), epidermal growth factor (EGF), granulocyte-macrophage colony stimulating factor (GM-CSF), erythropoietin (EPO) and calcitonin.
Hormones and growth factors influence cellular metabolism by binding to receptors. Receptors may be integral membrane proteins that are linked to signaling pathways within the cell, such as second messenger systems. Other classes of receptors are soluble molecules, such as the transcription factors.
Of particular interest are receptors for cytokines, molecules that promote the proliferation and/or differentiation of cells. Examples of cytokines include erythropoietin (EPO), which stimulates the development of red blood cells; thrombopoietin (TPO), which stimulates development of cells of the megakaryocyte lineage; and granulocyte-colony stimulating factor (G-CSF), which stimulates development of neutrophils. These cytokines are useful in restoring normal blood cell levels in patients suffering from anemia or receiving chemotherapy for cancer. The demonstrated in vivo activities of these cytokines illustrates the enormous clinical potential of, and need for, other cytokines, cytokine agonists, and cytokine antagonists.
SUMMARY OF THE INVENTION
The present invention addresses this need by providing a novel mammalian cytokine-like receptor called mammalian Zcytor5, and related compositions and methods. Within one aspect, the present invention provides an isolated human polynucleotide encoding a ligand-binding human receptor polypeptide. The polypeptide comprises a sequence of amino acids containing (a) the amino acid residues of SEQ ID NO: 17, residues 35 to 422 of SEQ ID NO:2; (b) allelic variants of (a); and (c) sequences that are at least 90%, 95% or 99% identical to (a) or (b). In an alternative embodiment, the polypeptide is comprised of amino acid residues 30 to and including amino acid residue 422 of SEQ ID NO:2.
The present invention also provides for a polynucleotide encoding another allelic variant of SEQ ID NO: 2 which is a human polypeptide receptor and is defined by SEQ ID NO: 4 in particular the polypeptide comprised of a sequence of amino acids containing (a) the amino acid residues of SEQ ID NO: 18, residues 34 to 425 of SEQ ID NO:4; (b) allelic variants of (a); and (c) sequences that are at least 90%, 95% or 99% identical to (a) or (b). In an alternative embodiment, the polypeptide is comprised of amino acid residues 29 to and including amino acid residue 425 of SEQ ID NO:4.
Other polynucleotides of the present invention encode the amino acid sequence of SEQ ID NO:21 which is a soluble receptor of SEQ ID NO:17 that does not contain a C-terminus phosphatidylinositol signal sequence; the amino acid sequence of SEQ ID NO: 20 is a Zcytor5 polypeptide of SEQ ID NO:2 having an alternative N-terminus cleavage site; SEQ ID NO: 22 which has an alternative N-terminus cleavage site of the Zcytor5 polypeptide of SEQ ID NO:4; SEQ ID NO:23 which is an amino acid of SEQ ID NO:18 that does not contain a C-terminus phosphatidylinositol signal sequence and the amino acid sequences defined by SEQ ID NOs: 24-31 which are variants of the Zcytor5 polypeptide of SEQ ID NO:4.
Another embodiment of the present invention is a polynucleotide which encodes rat Zcytor5. In particular, a polynucleotide is claimed which encodes a rat polypeptide containing (a) the amino acid sequence of SEQ ID NO: 19 residues 41 to 425 of SEQ ID NO:6; (b) allelic variants of (a); and (c) sequences that are at least 90%, 95% or 99% identical to (a) or (b).
Within a second aspect of the invention there is provided an expression vector comprising (a) a transcription promoter; (b) a DNA segment encoding a secretory peptide and a ligand-binding Zcyotor5 receptor polypeptide, containing an amino acid sequence as described above.
Within a third aspect of the invention there is provided a cultured eukaryotic cell into which has been introduced an expression vector as disclosed above, wherein said cell expresses a mammalian Zcytor5 receptor polypeptide encoded by the DNA segment.
Within a fourth aspect of the invention there is provided an isolated polypeptide. The polypeptide comprises a sequence of amino acids containing (a) the amino acid sequence of SEQ ID NO: 17, residues 35 to 422 of SEQ ID NO:2; (b) allelic variants of (a); and (c) sequences that are at least 90%, 95% or 99% identical to (a) or (b). In an alternative embodiment, the polypeptide is comprised of amino acid residues 30 to and including amino acid residue 422 of SEQ ID NO:2.
The present invention also provides for another allelic variant of SEQ ID NO: 2 which is a human polypeptide receptor and is defined by SEQ ID NO: 4 in particular the polypeptide is comprised of a sequence of amino acids containing (a) the amino acid sequence of SEQ ID NO: 18, residues 34 to 425 of SEQ ID NO:4; (b) allelic variants of (a); and (c) sequences that are at least 90%, 95% or 99% identical to (a) or (b). In an alternative embodiment, the polypeptide is comprised of residues 29 to 425 of SEQ ID NO: 4.
Another embodiment of the present invention is a rat Zcytor5 polypeptide containing (a) the amino acid sequence of SEQ ID NO: 19, residues 41 to 425 of SEQ ID NO:6; (b) allelic variants of (a); and (c) sequences that are at least 80% identical to (a) or (b).
Within a further aspect of the invention there is provided a chimeric polypeptide consisting essentially of a first portion and a second portion joined by a peptide bond. The first portion of the chimeric polypeptide consists essentially of a Zcytor5 receptor polypeptide as described above. The invention also provides expression vectors encoding the chimeric polypeptides and host cells transfected to produce the chimeric polypeptides.
The invention also provides a method for detecting a ligand within a test sample, comprising contacting a test sample with a Zcytor5 polypeptide as disclosed above, and detecting binding of the polypeptide to ligand in the sample. The polypeptide can be membrane bound within a cultured cell, wherein the detecting step comprises measuring a biological response in the cultured cell. Within another embodiment, the polypeptide is immobilized on a solid support.
Within an additional aspect of the invention there is provided an antibody that specifically binds to a polypeptide as disclosed above and an anti-idiotypic antibody of an antibody which specifically binds to a Zcytor5 antibody, also a method for producing an antibody to Zcytor5.
An additional embodiment of the present invention relates to a peptide or polypeptide which has the amino acid sequence of an epitope-bearing portion of a Zcytor5 polypeptide having an amino acid sequence described above. Peptides or polypeptides having the amino acid sequence of an epitope-bearing portion of a Zcytor5 polypeptide of the present invention include portions of such polypeptides with at least nine, preferably at least 15 and more preferably at least 30 to 50 amino acids, although epitope-bearing polypeptides of any length up to and including the entire amino acid sequence of a polypeptide of the present invention described above are also included in the present invention. Examples of said polypeptides are defined by the amino acid sequences of SEQ ID NOs: 32-37.
DETAILED DESCRIPTION OF THE INVENTION
The teachings of all of the references cited in the present specification are incorporated in their entirety herein by reference.
The term “affinity tag” is used herein to denote a polypeptide segment that can be attached to a second polypeptide to provide for purification or detection of the second polypeptid
Adams Robyn L.
Foster Donald C.
Gilbert Teresa
Jelmberg Anna C.
Lehner Joyce M.
Kemmerer Elizabeth
Lunn, Esq. Paul G.
Wegert Sandra
ZymoGenetics Inc.
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