Cytokine zcytor17 ligand polynucleotides
AssigneeZymoGenetics, Inc.
InventorsCindy Sprecher, Joseph Kuijper, Maria Dasovich, Francis Grant, Angela Hammond, Julia Novak, Jane Gross, Stacey Dillon
Life of this patent
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Abstract
The present invention relates to zcytor17lig polynucleotide, polypeptide and anti-zcytor17 antibody molecules. The zcytor17lig is a novel cytokine. The polypeptides may be used within methods for stimulating the immune system, and proliferation and/or development of hematopoietic cells in vitro and in vivo. The present invention also includes methods for producing the protein, uses therefor and antibodies thereto.
Claims55
An isolated polypeptide comprising a sequence of amino acid residues that is at least 90% identical to the sequence of amino acid residues selected from the group consisting of:
- (a) the polypeptide shown from residues 38 (Val) to 152 (Leu) as shown in SEQ ID NO:2;
- (b) the polypeptide shown from residues 27 (Leu) to 164 (Thr) as shown in SEQ ID NO:2;
- (c) the polypeptide shown from residues 24 (Thr) to 164 (Thr) as shown in SEQ ID NO:2;
- and
- (d) the polypeptide shown from residues 1 (Met) to 164 (Thr) as shown in SEQ ID NO:2.
An isolated polypeptide comprising at least 14 contiguous amino acid residues of SEQ ID NO:2 or SEQ ID NO:11.
A fusion protein comprising at least four polypeptides, wherein the order of polypeptides from N-terminus to C-terminus are:
- a first polypeptide that comprises a sequence of amino acid residues from 38-52 of SEQ ID NO:2;
- a first spacer of 6-27 amino acid residues;
- a second polypeptide that comprises a sequence of amino acid residues selected from the group consisting of:
- (a) IL-2 helix B amino acid residues of SEQ ID NO:168;
- (b) IL-4 helix B residues 65-83 of SEQ ID NO:164;
- (c) IL-3 helix B residues 73-86 of SEQ ID NO:102;
- (d) GM-CSF helix B residues 72-81 of SEQ ID NO:166;
- and
- (e) amino acid residues 83-98 of SEQ ID NO:2;
- a second spacer of 5-11 amino acid residues;
- a third polypeptide that comprises a sequence of amino acid residues selected from the group consisting of:
- (a) IL-2 helix C residues 102-116 of SEQ ID NO:162;
- (b) IL-4 helix C residues 94-118 of SEQ ID NO:164;
- (c) IL-3 helix C residues 91-103 of SEQ ID NO:102;
- (d) GM-CSF helix C residues 85-103 of SEQ ID NO:166;
- and
- (e) amino acid residues 104-117 of SEQ ID NO:2;
- a third spacer of 3-29 amino acid residues;
- and
- a fourth polypeptide that comprises a sequence of amino acid residues selected from the group consisting of:
- (a) IL-2 helix D residues 134-149 of SEQ ID NO:162;
- (b) IL-3 helix D residues 123-141 of SEQ ID NO:102;
- (c) IL-4 helix D residues 133-151 of SEQ ID NO:164;
- (d) GM-CSF helix D residues 120-131 of SEQ ID NO:166;
- and
- (e) amino acid residues 137-152 of SEQ ID NO:2.
A fusion protein comprising at least four polypeptides, wherein the order of polypeptides from N-terminus to C-terminus are:
- a first polypeptide that comprises a sequence of amino acid residues selected from a group consisting of:
- (a) IL-2 helix A residues 27-48 of SEQ ID NO:162;
- (b) IL-4 helix A residues 30-42 of SEQ ID NO:164;
- (c) IL-3 helix A residues 35-45 of SEQ ID NO:102;
- (d) GM-CSF helix A residues 30-44 of SEQ ID NO:166;
- and
- (e) amino acids residues 38-52 of SEQ ID NO:2;
- a first spacer of 6-27 amino acid residues;
- a second polypeptide that comprises a sequence of amino acid residues selected from the group consisting of:
- (a) IL-2 helix B residues of SEQ ID NO:168;
- (b);
- IL-4 helix B residues 65-83 of SEQ ID NO:164;
- (c) IL-3 helix B residues 73-86 of SEQ ID NO:102;
- (d) GM-CSF helix B residues 72-81 of SEQ ID NO:166;
- and
- (e) amino acid residues 83-98 of SEQ ID NO:2;
- a second spacer of 5-11 amino acid residues;
- a third polypeptide that comprises a sequence of amino acid residues selected from the group consisting of:
- (a) IL-2 helix C residues 102-116 of SEQ ID NO:162;
- (b) IL-4 helix C residues 94-118 of SEQ ID NO:164;
- (c) IL-3 helix C residues 91-103 of SEQ ID NO:102;
- (d) GM-CSF helix C residues 85-103 of SEQ ID NO:166;
- and
- (e) amino acid residues 104-117 of SEQ ID NO:2;
- a third spacer of 3-29 amino acid residues;
- and
- a fourth polypeptide that comprises a sequence of amino acid residues from 137-152 of SEQ ID NO:2.
An expression vector comprising the following operably linked elements:
- (a) a transcription promoter;
- (b) a DNA segment encoding a polypeptide comprising a sequence of amino acid residues selected from the group consisting of:
- (a) amino acid residues 38-52 of SEQ ID NO:2;
- (b) amino acid residues 83-98 of SEQ ID NO:2;
- (c) amino acid residues 104-117 of SEQ ID NO:2;
- and
- (d) amino acid residues 137-152 of SEQ ID NO:2;
- and
- (c) a transcription terminator.
An expression vector comprising the following operably linked elements:
- (a) a transcription promoter;
- (b) a DNA segment encoding a polypeptide comprising a sequence of amino acid residues that is at least 90% identical to residues 38 (Val) to 152 (Leu) as shown in SEQ ID NO:2;
- and
- (c) a transcription terminator.
An antibody which specifically binds to a polypeptide shown in SEQ ID NO:2 or SEQ ID NO:11.
A method of stimulating an immune response in a mammal exposed to an antigen or pathogen comprising the steps of:
- (1) determining directly or indirectly the level of antigen or pathogen present in said mammal;
- (2) administering a composition comprising zcytor17lig polypeptide in an acceptable pharmaceutical carrier;
- (3) determining directly or indirectly the level of antigen or pathogen in said mammal;
- and
- (4) comparing the level of the antigen or pathogen in step 1 to the antigen or pathogen level in step 3, wherein a change in the level is indicative of stimulating an immune response.
A method for expansion of hematopoietic cells and hematopoietic cell progenitors comprising culturing bone marrow or peripheral blood cells with a composition comprising an amount of zcytor17lig sufficient to produce an increase in the number of lymphoid cells in the bone marrow or peripheral blood cells as compared to bone marrow or peripheral blood cells cultured in the absence of zcytor17lig.
A method of stimulating 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 zcytor17lig polypeptide in an acceptable pharmaceutical carrier;
- (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 an increase in antibody level is indicative of stimulating an immune response.
An antibody or antibody fragment that specifically binds to a polypeptide of comprising a sequence of amino acid residues selected from the group consisting of:
- (a) the polypeptide shown from residues 38 (Val) to 152 (Leu) as shown in SEQ ID NO:2;
- (b) the polypeptide shown from residues 27 (Leu) to 164 (Thr) as shown in SEQ ID NO:2;
- (c) the polypeptide shown from residues 24 (Thr) to 164 (Thr) as shown in SEQ ID NO:2;
- and
- (d) the polypeptide shown from residues 1 (Met) to 164 (Thr) as shown in SEQ ID NO:2.
A method of treating a mammal afflicted with an inflammatory disease in which zcytor17lig plays a role, comprising:
- administering an antagonist of zcytor17lig to the mammal such that the inflammation is reduced, wherein the antagonist is selected from the group consisting of an antibody or binding polypeptide that specifically binds a polypeptide or polypeptide fragment of zcytor17lig (SEQ ID NO:2).
A method for detecting inflammation in a patient, comprising:
- obtaining a tissue or biological sample from a patient;
- labeling a polynucleotide comprising at least 14 contiguous nucleotides of SEQ ID NO:1 or the complement of SEQ ID NO:1;
- incubating the tissue or biological sample with under conditions wherein the polynucleotide will hybridize to complementary polynucleotide sequence;
- visualizing the labeled polynucleotide in the tissue or biological sample;
- and
- comparing the level of labeled polynucleotide hybridization in the tissue or biological sample from the patient to a normal control tissue or biological sample,
- wherein an increase in the labeled polynucleotide hybridization to the patient tissue or biological sample relative to the normal control tissue or biological sample is indicative of inflammation in the patient.
An isolated polynucleotide encoding a polypeptide comprising a sequence of amino acid residues from residue 27 to residue 164 as shown in SEQ ID NO:
- 2.
An isolated polynucleotide encoding a polypeptide consisting of the sequence of amino acid residues from residue 27 to residue 164 as shown in SEQ ID NO:
- 2.
An isolated polynucleotide encoding a polypeptide consisting of a sequence of amino acid residues from residue 1 to residue 164 as shown in SEQ ID NO:
- 2.
Dependencies are inferred from the claim text.