Cytokine zalpha11 ligand

Abstract

Antibodies that bind to polypeptides and peptides comprising the sequence of zalpha11 Ligand as shown in SEQ ID NO: 2 are described. The antibodies may bind the full length sequence of 162 amino acid residues or a fragment thereof, including a mature polypeptide of 131 amino acid residues and smaller polypeptide and peptide sequences. The antibodies may include antibodies that are polyclonal, monoclonal, murine, humanized or neutralizing. Methods for producing the antibodies are also described.

1 - 4 . (canceled) 
     
     
         5 . 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. 
   
     
     
         6 . 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.   
     
     
         7 . A fusion protein according to  claim 5 , wherein the fourth polypeptide comprises amino acid residues 135-148 of SEQ ID NO: 2. 
     
     
         8 . 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 from 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. 
   
     
     
         9 . 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 from 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. 
   
     
     
         10 . A method for preparing a fusion protein according to  claim 5  wherein said method comprises joining the polypeptide components of the fusion protein by chemical conjugation. 
     
     
         11 . A method of preparing a fusion protein according to any of  claim 5  wherein said method comprises expressing a single polynucleotide construct that encodes the polypeptide components of the fusion protein in the correct reading frame. 
     
     
         12 . A polypeptide selected from the group consisting of:
 a) the polypeptide consisting of the amino acid sequence of SEQ ID NO: 72;   b) the polypeptide consisting of the amino acid sequence of SEQ ID NO: 73;   
       for use in a method of producing an antibody in a non-human animal. 
     
     
         13 . A polypeptide selected from the group consisting of:
 a) an isolated polypeptide 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 zalpha11 receptor as shown in SEQ ID NO: 115;   b) an isolated polypeptide at least 90% identical to residues 32 (Gln) to 162 (Ser) as shown in SEQ ID NO:2 wherein the polypeptide binds a zalpha11 receptor as shown in SEQ ID NO: 115;   c) an isolated polypeptide 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 zalpha11 receptor as shown in SEQ ID NO: 115 and wherein amino acid residues 71, 78, 122, and 125 are cysteine;   d) an isolated polypeptide at least 95% 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 zalpha11 receptor as shown in SEQ ID NO: 115;   e) an isolated polypeptide wherein the sequence of amino acid residues is 100% identical to SEQ ID NO: 2 from residues 41 (Gln) to 148 (Ile);   f) an isolated polypeptide at least 95% identical to residues 32 (Gln) to 162 (Ser) as shown in SEQ ID NO: 2 wherein the polypeptide binds a zalpha11 receptor as shown in SEQ ID NO: 115;   g) an isolated polypeptide wherein the sequence of amino acid residues is as shown in SEQ ID NO: 2 from residue 32 (Gln) to residue 162 (Ser) wherein the polypeptide binds a zalpha11 receptor as shown in SEQ ID NO: 115;   h) an isolated polypeptide wherein the sequence of amino acid residues is as shown in SEQ ID NO: 2 from residue 1 (Met) to residue 162 (Ser) wherein the polypeptide binds a zalpha11 receptor as shown in SEQ ID NO: 115;   i) an isolated polypeptide wherein the sequence of amino acid residues is as shown in SEQ ID NO: 56 from residue 23 (Gln) to residue 146 (Ser) wherein the polypeptide binds a zalpha11 receptor as shown in SEQ ID NO: 115;   j) an isolated polypeptide wherein the sequence of amino acid residues is as shown in SEQ ID NO: 56 from residue 1 (Met) to residue 146 (Ser) wherein the polypeptide binds a zalpha11 receptor as shown in SEQ ID NO: 115;   for use in a method of producing an antibody in a non-human animal.   
     
     
         14 . A polypeptide selected from the group consisting of:
 a) the polypeptide consisting of the amino acid sequence of SEQ ID NO: 2 from amino acid number 114 to 119;   b) the polypeptide consisting of the amino acid sequence of SEQ ID NO: 2 from amino acid number 126 to 131;   c) the polypeptide consisting of the amino acid sequence of SEQ ID NO: 2 from amino acid number 101 to 105;   d) the polypeptide consisting of the amino acid sequence of SEQ ID NO: 2 from amino acid number 113 to 118;   e) the polypeptide consisting of the amino acid sequence of SEQ ID NO: 2 from amino acid number 158 to 162;   for use in a method of producing an antibody in a non-human animal.   
     
     
         15 . An in vitro method for detecting a genetic abnormality or aberration in the zalpha11 ligand gene of a patient, wherein said genetic abnormality or aberration is selected from aneuploidy, a gene copy number change, loss of heterogeneity, a translocation, an insertion, a deletion, a restriction site change, or a chromosome rearrangement; wherein said method comprises:
 a) incubating a genetic sample from said patient with a polynucleotide probe or primer comprising a portion of SEQ ID NO: 1, the complement of SEQ ID NO: 1 or an RNA equivalent thereof, wherein said probe or primer hybridizes to complementary polynucleotide sequence, to produce a first reaction product;   b) visualising said first reaction product; and   c) comparing the visualised first reaction product with a second control reaction product of a control genetic sample, wherein a difference between the first reaction product and the second control product is indicative of a genetic abnormality or aberration in said patient.   
     
     
         16 . An in vitro method for detecting a cancer in a patient, wherein said cancer is selected from a lymphoid, B cell, epithelial or hematopoietic cancer; wherein said method comprises:
 a) measuring the expression of a polypeptide comprising SEQ ID NO: 2, or comprising residues 32-162 of SEQ ID NO: 2, in a cell or tissue sample from the patient; and   b) comparing the expression of said polypeptide in the patient sample with the expression of said polypeptide in a control cell or tissue sample, wherein gain or loss of expression of the polypeptide in the patient sample as compared with the control sample is indicative of cancer in the patient.