Interferon-like molecules and uses thereof

Abstract

The present invention provides Interferon-Like (IFN-L) polypeptides and nucleic acid molecules encoding the same. The invention also provides selective binding agents, vectors, host cells, and methods for producing IFN-L polypeptides. The invention further provides pharmaceutical compositions and methods for the diagnosis, treatment, amelioration, and/or prevention of diseases, disorders, and conditions associated with IFN-L polypeptides.

What is claimed is:  
     
         1 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) the amino acid sequence as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5; and    (b) the amino acid sequence encoded by the DNA insert in ATCC Deposit No. PTA-976.    
     
     
         2 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) the amino acid sequence as set forth in either SEQ ID NO: 3 or SEQ ID NO: 6, optionally further comprising an amino-terminal methionine;    (b) an amino acid sequence for an ortholog of either SEQ ID NO: 2 or SEQ ID NO:5;    (c) an amino acid sequence that is at least about 70 percent identical to the amino acid sequence of either SEQ ID NO: 2 or SEQ ID NO: 5, wherein the polypeptide has an activity of the polypeptide set forth in either SEQ ID NO: 2 or SEQ ID NO: 5;    (d) a fragment of the amino acid sequence set forth in either SEQ ID NO: 2 or SEQ ID NO: 5 comprising at least about 25 amino acid residues, wherein the fragment has an activity of the polypeptide set forth in either SEQ ID NO: 2 or SEQ ID NO: 5, or is antigenic; and    (e) an amino acid sequence for an allelic variant or splice variant of the amino acid sequence as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5, the amino acid sequence encoded by the DNA insert in ATCC Deposit No. PTA-976, or the amino acid sequence of any of (a)-(c).    
     
     
         3 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) the amino acid sequence as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5 with at least one conservative amino acid substitution, wherein the polypeptide has an activity of the polypeptide set forth in either SEQ ID NO: 2 or SEQ ID NO: 5;    (b) the amino acid sequence as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5 with at least one amino acid insertion, wherein the polypeptide has an activity of the polypeptide set forth in either SEQ ID NO: 2 or SEQ ID NO: 5;    (c) the amino acid sequence as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5 with at least one amino acid deletion, wherein the polypeptide has an activity of the polypeptide set forth in either SEQ ID NO: 2 or SEQ ID NO: 5;    (d) the amino acid sequence as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5 that has a C- and/or N-terminal truncation, wherein the polypeptide has an activity of the polypeptide set forth in either SEQ ID NO: 2 or SEQ ID NO: 5; and    (e) the amino acid sequence as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5 with at least one modification selected from the group consisting of amino acid substitutions, amino acid insertions, amino acid deletions, C-terminal truncation, and N-terminal truncation, wherein the polypeptide has an activity of the polypeptide set forth in either SEQ ID NO: 2 or SEQ ID NO: 5.    
     
     
         4 . An isolated polypeptide encoded by a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of: 
 (a) the nucleotide sequence as set forth in either SEQ ID NO: 1 or SEQ ID NO: 4;    (b) the nucleotide sequence of the DNA insert in ATCC Deposit No. PTA-976;    (c) a nucleotide sequence encoding the polypeptide as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5; and    (d) a nucleotide sequence that hybridizes under at least moderately stringent conditions to the complement of any of (a)-(c); wherein the polypeptide has an activity of the polypeptide set forth in either SEQ ID NO: 2 or SEQ ID NO: 5.    
     
     
         5 . An isolated polypeptide encoded by a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of: 
 (a) a nucleotide sequence encoding a polypeptide that is at least about 70 percent identical to the polypeptide as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5;    (b) a nucleotide sequence encoding an allelic variant or splice variant of the nucleotide sequence as set forth in either SEQ ID NO: 1 or SEQ ID NO: 4, the nucleotide sequence of the DNA insert in ATCC Deposit No. PTA-976, or the nucleotide sequence of (a);    (c) a region of the nucleotide sequence of either SEQ ID NO: 1 or SEQ ID NO: 4, the DNA insert in ATCC Deposit No. PTA-976, or the nucleotide sequence of (a) or (b), encoding a polypeptide fragment of at least about 25 amino acid residues;    (d) a region of the nucleotide sequence of either SEQ ID NO: 1 or SEQ ID NO: 4, the DNA insert in ATCC Deposit No. PTA-976, or the nucleotide sequence of any of (a)-(c), comprising a fragment of at least about 16 nucleotides; and    (e) a nucleotide sequence that hybridizes under at least moderately stringent conditions to the complement of any of (a)-(d); wherein the polypeptide has an activity of the polypeptide set forth in either SEQ ID NO: 2 or SEQ ID NO: 5.    
     
     
         6 . An isolated polypeptide encoded by a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of: 
 (a) a nucleotide sequence encoding a polypeptide as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5 with at least one conservative amino acid substitution;    (b) a nucleotide sequence encoding a polypeptide as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5 with at least one amino acid insertion;    (c) a nucleotide sequence encoding a polypeptide as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5 with at least one amino acid deletion;    (d) a nucleotide sequence encoding a polypeptide as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5 that has a C- and/or N-terminal truncation;    (e) a nucleotide sequence encoding a polypeptide as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5 with at least one modification selected from the group consisting of amino acid substitutions, amino acid insertions, amino acid deletions, C-terminal truncation, and N-terminal truncation;    (f) a nucleotide sequence of any of (a)-(e) comprising a fragment of at least about 16 nucleotides; and    (g) a nucleotide sequence that hybridizes under at least moderately stringent conditions to the complement of any of (a)-(f);    wherein the polypeptide has an activity of the polypeptide set forth in either SEQ ID NO: 2 or SEQ ID NO: 5.    
     
     
         7 . The isolated polypeptide according to  claim 2  or  3 , wherein the percent identity is determined using a computer program selected from the group consisting of GAP, BLASTP, FASTA, BLASTA, BLASTX, BestFit, and the Smith-Waterman algorithm.  
     
     
         8 . A composition comprising the polypeptide of any of claims  1 ,  2 , or  3 , and a pharmaceutically acceptable formulation agent.  
     
     
         9 . The composition of  claim 8 , wherein the pharmaceutically acceptable formulation agent is a carrier, adjuvant, solubilizer, stabilizer, or anti-oxidant.  
     
     
         10 . The composition of  claim 8 , wherein the polypeptide comprises the amino acid sequence as set forth in either SEQ ID NO: 3 or SEQ ID NO: 6.  
     
     
         11 . A polypeptide comprising a derivative of the polypeptide of any of claims  1 ,  2 , or  3 .  
     
     
         12 . The polypeptide of  claim 11  that is covalently modified with a water-soluble polymer.  
     
     
         13 . The polypeptide of  claim 12 , wherein the water-soluble polymer is selected from the group consisting of polyethylene glycol, monomethoxy-polyethylene glycol, dextran, cellulose, poly-(N-vinyl pyrrolidone) polyethylene glycol, propylene glycol homopolymers, polypropylene oxide/ethylene oxide co-polymers, polyoxyethylated polyols, and polyvinyl alcohol.  
     
     
         14 . A fusion polypeptide comprising the polypeptide of any of claims  1 ,  2 , or  3  fused to a heterologous amino acid sequence.  
     
     
         15 . The fusion polypeptide of  claim 14 , wherein the heterologous amino acid sequence is an IgG constant domain or fragment thereof.  
     
     
         16 . A polypeptide produced by a process comprising culturing a host cell comprising a vector comprising a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of: 
 (a) the nucleotide sequence as set forth in either SEQ ID NO: 1 or SEQ ID NO: 4;    (b) the nucleotide sequence of the DNA insert in ATCC Deposit No. PTA-976;    (c) a nucleotide sequence encoding the polypeptide as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5; and    (d) a nucleotide sequence that hybridizes under at least moderately stringent conditions to the complement of any of (a)-(c); under suitable conditions to express the polypeptide, and optionally isolating the polypeptide from the culture.    
     
     
         17 . A polypeptide produced by a process comprising culturing a host cell comprising a vector comprising a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of: 
 (a) a nucleotide sequence encoding a polypeptide that is at least about 70 percent identical to the polypeptide as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5, wherein the encoded polypeptide has an activity of the polypeptide set forth in either SEQ ID NO: 2 or SEQ ID NO: 5;    (b) a nucleotide sequence encoding an allelic variant or splice variant of the nucleotide sequence as set forth in either SEQ ID NO: 1 or SEQ ID NO: 4, the nucleotide sequence of the DNA insert in ATCC Deposit No. PTA-976, or the nucleotide sequence of (a);    (c) a region of the nucleotide sequence of either SEQ ID NO: 1 or SEQ ID NO: 4, the DNA insert in ATCC Deposit No. PTA-976, the nucleotide sequence (a) or (b), encoding a polypeptide fragment of at least about 25 amino acid residues, wherein the polypeptide fragment has an activity of the encoded polypeptide as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5, or is antigenic;    (d) a region of the nucleotide sequence of either SEQ ID NO: 1 or SEQ ID NO: 4, the DNA insert in ATCC Deposit No. PTA-976, or the nucleotide sequence of any of (a)-(c), comprising a fragment of at least about 16 nucleotides; and    (e) a nucleotide sequence that hybridizes under at least moderately stringent conditions to the complement of any of (a)-(d); under suitable conditions to express the polypeptide, and optionally isolating the polypeptide from the culture.    
     
     
         18 . A polypeptide produced by a process comprising culturing a host cell comprising a vector comprising a nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of: 
 (a) a nucleotide sequence encoding a polypeptide as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5 with at least one conservative amino acid substitution, wherein the encoded polypeptide has an activity of the polypeptide set forth in either SEQ ID NO: 2 or SEQ ID NO: 5;    (b) a nucleotide sequence encoding a polypeptide as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5 with at least one amino acid insertion, wherein the encoded polypeptide has an activity of the polypeptide set forth in either SEQ ID NO: 2 or SEQ ID NO: 5;    (c) a nucleotide sequence encoding a polypeptide as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5 with at least one amino acid deletion, wherein the encoded polypeptide has an activity of the polypeptide set forth in either SEQ ID NO: 2 or SEQ ID NO: 5;    (d) a nucleotide sequence encoding a polypeptide as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5 that has a C- and/or N-terminal truncation, wherein the encoded polypeptide has an activity of the polypeptide set forth in either SEQ ID NO:2or SEQ ID NO: 5;    (e) a nucleotide sequence encoding a polypeptide as set forth in either SEQ ID NO: 2 or SEQ ID NO: 5 with at least one modification selected from the group consisting of amino acid substitutions, amino acid insertions, amino acid deletions, C-terminal truncation, and N-terminal truncation, wherein the encoded polypeptide has an activity of the polypeptide set forth in either SEQ ID NO: 2 or SEQ ID NO: 5;    (f) a nucleotide sequence of any of (a)-(e) comprising a fragment of at least about 16 nucleotides; and    (g) a nucleotide sequence that hybridizes under at least moderately stringent conditions to the complement of any of (a)-(f); under suitable conditions to express the polypeptide, and optionally isolating the polypeptide from the culture.    
     
     
         19 . The polypeptide of any of claims  16 ,  17 , or  18 , wherein the host cell is a eukaryotic cell.  
     
     
         20 . The polypeptide of any of claims  16 ,  17 , or  18 , wherein the host cell is a prokaryotic cell.