Novel cytokine zalpha11 ligand
AssigneeZymoGenetics, Inc.
InventorsJulia E. Novak, Scott R. Presnell, Cindy A. Sprecher, Donald C. Foster, Richard D. Holly, Jane A. Gross, Janet V. Johnston, Andrew J. Nelson, Stacey R. Dillon, Angela K. Hammond
Life of this patent
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Abstract
The present invention relates to zalpha11 Ligand polynucleotide and polypeptide molecules. The zalpha11 Ligand is a novel cytokine. The polypeptides may be used within methods for stimulating the 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.
Claims54
An isolated polypeptide comprising a sequence of amino acid residues that is at least 90% identical to residues 41 (Gln) to 148 (Ile) as shown in SEQ ID NO:
- 2, wherein the residue at position 44 is Asp, the residue at position 47 is Asp and the residue at position 135 is Glu.
An isolated polypeptide comprising a sequence of amino acid residues as shown in SEQ ID NO:
- 2 from residue 32 (Gln) to residue 162 (Ser) or as shown in SEQ ID NO:
- 56 (Mouse) from residue 23 (Gln) to residue 146 (Ser).
An isolated polypeptide comprising at least 14 contiguous amino acid residues of SEQ ID NO:
- 2 or SEQ ID NO:
- 56.
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 41 to 56 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 53-75 of SEQ ID NO:
- 111;
- (b) IL-4 helix B residues 65-83 of SEQ ID NO:
- 112;
- (c) IL-15 helix B residues 84-101 of SEQ ID NO:
- 113;
- (d) GMCSF helix B residues 72-81 of SEQ ID NO:
- 114;
- and
- (e) amino acid residues 69-84 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 87-99 of SEQ ID NO:
- 111;
- (b) IL-4 helix C residues 95-118 of SEQ ID NO:
- 112;
- (c) IL-15 helix C residues 107-119 of SEQ ID NO:
- 113;
- (d) GMCSF helix C residues 91-102 of SEQ ID NO:
- 114;
- and
- (e) amino acid residues 92-105 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 103-121 of SEQ ID NO:
- 111;
- (b) IL-15 helix D residues 134-157 of SEQ ID NO:
- 112;
- (c) IL-4 helix D residues 134-160 of SEQ ID NO:
- 113;
- (d) GMCSF helix D residues 120-131 of SEQ ID NO:
- 114;
- and
- (e) amino acid residues 135-148 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 36-46 of SEQ ID NO:
- 111;
- (b) IL-4 helix A residues 29-43 of SEQ ID NO:
- 112;
- (c) IL-15 helix A residues 45-68 of SEQ ID NO:
- 113;
- (d) GMCSF helix A residues 30-44 of SEQ ID NO:
- 114;
- and
- (e) amino acids residues 41-56 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 53-75 of SEQ ID NO:
- 111;
- (b);
- IL-4 helix B residues 65-83 of SEQ ID NO:
- 112;
- (c) IL-15 helix B residues 84-101 of SEQ ID NO:
- 113;
- (d) GMCSF helix B residues 72-81 of SEQ ID NO:
- 114;
- and
- (e) amino acid residues 69-84 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 87-99 of SEQ ID NO:
- 111;
- (b) IL-4 helix C residues 95-118 of SEQ ID NO:
- 112;
- (c) IL-15 helix C residues 107-119 of SEQ ID NO:
- 113;
- (d) GMCSF helix C residues 91-102 of SEQ ID NO:
- 114;
- and
- (e) amino acid residues 92-105 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 135-148 of SEQ ID NO:
- 2.
An isolated polynucleotide molecule comprising a sequence of nucleotides that encode the polypeptide as shown in SEQ ID NO:
- 2 from residue 32 to residue 162 or as shown in SEQ ID NO:
- 56 from residue 23 to residue 146.
An isolated polynucleotide molecule comprising a sequence of nucleotides that encode the polypeptide as shown in SEQ ID NO:
- 2 from residue 1 to residue 162 or as shown in SEQ ID NO:
- 56 from residue 1 to residue 146.
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 41-56 of SEQ ID NO:
- 2;
- (b) amino acid residues 69-84 of SEQ ID NO:
- 2;
- (c) amino acid residues 92-105 of SEQ ID NO:
- 2;
- and
- (d) amino acid residues 135-148 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 41 (Gln) to 148 (Ile) as shown in SEQ ID NO:
- 2, wherein the residue at position 44 is Asp, the residue at position 47 is Asp and the residue at position 135 is Glu;
- 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 amino acid residues 32 (Gln) to 162 (Ser) of SEQ ID NO:
- 2;
- and
- (c) a transcription terminator.
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 zalpha11 Ligand polypeptide in an acceptable pharmaceutical vehicle;
- (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 zalpha11 Ligand 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 zalpha11 Ligand.
32 The method of claim 31, wherein the hematopoietic cells and hemopoietic progenitor cells are lymphoid cells.
The method of claim 32, wherein the lymphoid cells are NK cells or cytotoxic T cells.
A method of reducing proliferation of neoplastic B or T cells comprising administering to a mammal with a B or T cell neoplasm an amount of a composition of zalpha11 Ligand sufficient to reduce proliferation of the neoplastic B or T cells.
A method of reducing proliferation of neoplastic B or T cells comprising administering to a mammal with a B or T cell neoplasm an amount of a composition of zalpha11 Ligand antagonist sufficient to reducing proliferation of the neoplastic B or T cells.
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 zalpha11 Ligand 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 an increase in antibody level is indicative of stimulating an immune response.
An isolated polynucleotide molecule comprising a sequence of nucleotides that encode an isolated polypeptide comprising a sequence of amino acid residues that is at least 90% identical to residues 41 (Gln) to 148 (Ile) as shown in SEQ ID NO:2, wherein the residue at position 44 is Asp, the residue at position 47 is Asp and the residue at position 135 is Glu, wherein the polypeptide binds a receptor as shown in SEQ ID NO:
- 115.
An isolated polynucleotide molecule comprising a sequence of nucleotides that encode for an isolated polypeptide comprising at least 14 contiguous amino acid residues of SEQ ID NO:2 or SEQ ID NO:56, wherein said polypeptide stimulates an antigenic response in a mammal.
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 41-56 of SEQ ID NO:
- 2;
- (b) amino acid residues 69-84 of SEQ ID NO:
- 2;
- (c) amino acid residues 92-105 of SEQ ID NO:
- 2;
- and
- (d) amino acid residues 135-148 of SEQ ID NO:
- 2;
- wherein said DNA segment encodes for a polypeptide that stimulates an antigenic response in a mammal;
- 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 41 (Gln) to 148 (Ile) as shown in SEQ ID NO:
- 2, wherein the residue at position 44 is Asp, the residue at position 47 is Asp and the residue at position 135 is Glu, wherein the polypeptide binds a receptor as shown in SEQ ID NO:
- 115;
- and
- (c) a transcription terminator.
Dependencies are inferred from the claim text.