Soluble Zcytor11 cytokine receptors
AssigneeZymoGenetics, Inc.
InventorsWayne R. Kindsvogel, Stavros Topouzis
Life of this patent
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Abstract
Novel polypeptide combinations, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed for soluble zcytor11 receptors that may be used as novel cytokine antagonists, and within methods for detecting ligands that stimulate the proliferation and/or development of hematopoietic, lymphoid and myeloid cells in vitro and in vivo. Ligand-binding receptor polypeptides and antibodies can also be used to block TIF activity in vitro and in vivo, and may be used in conjunction with TIF and other cytokines to selectively stimulate the immune system. The present invention also includes methods for producing the protein, uses therefor and antibodies thereto.
Claims47
An isolated polynucleotide that encodes a soluble cytokine receptor polypeptide comprising a sequence of amino acid residues that is at least 90% identical to the amino acid sequence as shown in SEQ ID NO:3, and
- wherein the soluble cytokine receptor polypeptide encoded by the polynucleotide sequence binds or antagonizes IL-TIF (SEQ ID NO:8).
An isolated polynucleotide that encodes a soluble cytokine receptor polypeptide comprising a sequence of amino acid residues that is at least 90% identical to the amino acid sequence as shown in SEQ ID NO:3, wherein the soluble cytokine receptor polypeptide encoded by the polynucleotide forms a heterodimeric or multimeric receptor complex.
An isolated polynucleotide that encodes a soluble cytokine receptor polypeptide comprising a sequence of amino acid residues as shown in SEQ ID NO:3, wherein the soluble cytokine receptor polypeptide encoded by the polynucleotide forms a heterodimeric or multimeric receptor complex.
An expression vector comprising the following operably linked elements:
- (a) a transcription promoter;
- a first DNA segment encoding a soluble cytokine receptor polypeptide having an amino acid sequence as shown in SEQ ID NO:3;
- and a transcription terminator;
- and
- (b) a second transcription promoter;
- a second DNA segment encoding a soluble Class I or Class II cytokine receptor polypeptide;
- and a transcription terminator;
- and
- wherein the first and second DNA segments are contained within a single expression vector or are contained within independent expression vectors.
A DNA construct encoding a fusion protein comprising:
- a first DNA segment encoding a polypeptide having a sequence of amino acid residues as shown in SEQ ID NO:3;
- and
- at least one other DNA segment encoding a soluble Class I or Class II cytokine receptor polypeptide,
- wherein the first and other DNA segments are connected in-frame;
- and
- wherein the first and other DNA segments encode the fusion protein.
An isolated soluble cytokine receptor polypeptide comprising a sequence of amino acid residues that is at least 90% identical to an amino acid sequence as shown in SEQ ID NO:3, and
- wherein the soluble cytokine receptor polypeptide binds IL-TIF or antagonizes IL-TIF activity.
An isolated polypeptide comprising a sequence of amino acid residues that is at least 90% identical to an amino acid sequence as shown in SEQ ID NO:3, wherein the soluble cytokine receptor polypeptide forms a heterodimeric or multimeric receptor complex.
An isolated soluble cytokine receptor polypeptide comprising a sequence of amino acid residues as shown in SEQ ID NO:3, wherein the soluble cytokine receptor polypeptide forms a heterodimeric or multimeric receptor complex.
An isolated heterodimeric or multimeric soluble receptor complex comprising soluble receptor subunits, wherein at least one of soluble receptor subunits comprises a soluble cytokine receptor polypeptide comprising a sequence of amino acid residues as shown in SEQ ID NO:3.
A method of producing an antibody to soluble cytokine receptor polypeptide comprising:
- inoculating an animal with a soluble cytokine receptor polypeptide selected from the group consisting of:
- (a) a polypeptide comprising a homodimeric soluble cytokine receptor complex;
- (b) a polypeptide comprising a soluble cytokine receptor heterodimeric or multimeric receptor complex comprising a soluble Class I or Class II cytokine receptor polypeptide;
- (c) a polypeptide comprising a soluble cytokine receptor heterodimeric or multimeric receptor complex comprising a soluble CRF2-4 receptor polypeptide (SEQ ID NO:33);
- (d) a polypeptide comprising a soluble cytokine receptor heterodimeric or multimeric receptor complex comprising a soluble IL-10 receptor polypeptide (SEQ ID NO:34);
- (e) a polypeptide comprising a soluble cytokine receptor heterodimeric or multimeric receptor complex comprising a soluble DIRS1 receptor polypeptide (SEQ ID NO:35);
- and
- wherein the polypeptide elicits an immune response in the animal to produce the antibody;
- and
- isolating the antibody from the animal.
A method for inhibiting IL-TIF-induced proliferation of hematopoietic cells and hematopoietic cell progenitors comprising culturing bone marrow or peripheral blood cells with a composition comprising an amount of soluble cytokine receptor sufficient to reduce proliferation of the hematopoietic cells in the bone marrow or peripheral blood cells as compared to bone marrow or peripheral blood cells cultured in the absence of soluble cytokine receptor.
A method of reducing IL-TIF-induced or IL-9 induced inflammation comprising administering to a mammal with inflammation an amount of a composition of soluble cytokine receptor sufficient to reduce inflammation.
A method of suppressing an immune response in a mammal exposed to an antigen or pathogen comprising:
- (1) determining a level of an antigen- or pathogen-specific antibody;
- (2) administering a composition comprising soluble cytokine receptor polypeptide in an acceptable pharmaceutical vehicle;
- (3) determining a post administration level of antigen- or pathogen-specific antibody;
- (4) comparing the level of antibody in step (1) to the level of antibody in step (3), wherein a lack of increase or a decrease in antibody level is indicative of suppressing an immune response.
Dependencies are inferred from the claim text.