Chimeric polypeptides and uses thereof

Abstract

The invention provides novel peptides (e.g., linkers) and polypeptide compositions comprising the linkers (e.g., fusion proteins) and methods of using the polypeptide compositions. Peptides (e.g., linkers) are useful as tags and for engineering fusion proteins (e.g., antigen binding molecules, scFv). Polypeptide linkers described herein facilitate flexibility of linked peptides allowing for proper folding, conformation and reduced immunogenicity.

1 . A peptide comprising 6-20 amino acids and a consensus sequence BPXXXZ, wherein each X is independently a glycine (G) or serine (S), B is a positively charged amino acid and Z is glycine (G) or a negatively charged amino acid and wherein the peptide is not GSTSGSGKPGSGEGSTKG (SEQ ID NO: 1), GSGKPGSGEG (SEQ ID NO: 13), GKPGSGEG (SEQ ID NO: 14), or SGKPGSGE (SEQ ID NO: 15). 
     
     
         2 . (canceled) 
     
     
         3 . The peptide of  claim 1 , wherein B is lysine (K) or arginine (R). 
     
     
         4 - 5 . (canceled) 
     
     
         6 . The peptide of  claim 1 , wherein Z is a negatively charged amino acid selected from glutamic acid (ε) or aspartic acid (D). 
     
     
         7 . (canceled) 
     
     
         8 . The peptide of  claim 1 , wherein the consensus sequence is GKPGSGE (SEQ ID NO: 5), GKPGSGG (SEQ ID NO: 6) or GSGKPGSGEGG (SEQ ID NO: 31). 
     
     
         9 - 10 . (canceled) 
     
     
         11 . The peptide of  claim 1 , wherein the peptide comprises an amino acid sequence of GGGSGKPGSGEGGGS (SEQ ID NO: 7). 
     
     
         12 . The peptide of  claim 1 , wherein the peptide comprises an amino acid sequence of GGGSGKPGSGEGGGGS (SEQ ID NO: 8). 
     
     
         13 . The peptide of  claim 1 , wherein the peptide comprises an amino acid sequence of GGGGSGKPGSGGGGS (SEQ ID NO: 9). 
     
     
         14 . The peptide of  claim 1 , wherein the peptide comprises an amino acid sequence of GGGGSGKPGSGEGGS (SEQ ID NO: 10). 
     
     
         15 . The peptide of  claim 1 , wherein the peptide comprises an amino acid sequence of GGGGSGKPGSGEGGGS (SEQ ID NO: 11). 
     
     
         16 . The peptide of  claim 1 , wherein the peptide comprises an amino acid sequence of GGGGSGKPGSGEGGGGS (SEQ ID NO: 12). 
     
     
         17 . The peptide of  claim 1 , wherein the peptide comprises an amino acid sequence of STSGSGKPGSGEGST (SEQ ID NO: 17). 
     
     
         18 . A peptide comprising 8-20 amino acids and an amino acid sequence at least 80% identical to any one of GGGSGKPGSGEGGGS (SEQ ID NO: 7), GGGSGKPGSGEGGGGS (SEQ ID NO:8), GGGGSGKPGSGGGGS (SEQ ID NO: 9), GGGGSGKPGSGEGGS (SEQ ID NO: 10), GGGGSGKPGSGEGGGS (SEQ ID NO: 11), GGGGSGKPGSGEGGGGS (SEQ ID NO: 12), STSGSGKPGSGEGST (SEQ ID NO: 17), GGGGSGGGGSGGGGSG (SEQ ID NO: 18), GGGGGSGGGGSGGGGS (SEQ ID NO: 19), or GGGGSGGGGSGGGGGS (SEQ ID NO: 20). 
     
     
         19 . A peptide comprising 8-20 amino acids and an amino acid sequence that contains at least six (6) identical amino acids out of ten (10) contiguous amino acids found in any one of GGGSGKPGSGEGGGS (SEQ ID NO: 7), GGGSGKPGSGEGGGGS (SEQ ID NO: 8), GGGGSGKPGSGGGGS (SEQ ID NO: 9), GGGGSGKPGSGEGGS (SEQ ID NO: 10), GGGGSGKPGSGEGGGS (SEQ ID NO: 11), GGGGSGKPGSGEGGGGS (SEQ ID NO: 12), STSGSGKPGSGEGST (SEQ ID NO: 17), GGGGSGGGGSGGGGSG (SEQ ID NO: 18) GGGGGSGGGGSGGGGS (SEQ ID NO: 19), or GGGGSGGGGSGGGGGS (SEQ ID NO: 20). 
     
     
         20 . A peptide comprising the amino acid sequence GGGGSGGGGSGGGGSG (SEQ ID NO: 18), GGGGGSGGGGSGGGGS (SEQ ID NO: 19), or GGGGSGGGGSGGGGGS (SEQ ID NO: 20). 
     
     
         21 . A fusion protein comprising:
 a) a first polypeptide; and   b) a peptide according to  claim 1 .   
     
     
         22 . (canceled) 
     
     
         23 . The fusion protein of  claim 21 , wherein the fusion protein is an antigen binding molecule comprising a light chain variable domain and a heavy chain variable domain. 
     
     
         24 - 25 . (canceled) 
     
     
         26 . A polynucleotide encoding a peptide according to  claim 1 . 
     
     
         27 . A polynucleotide encoding the fusion protein of  claim 21 . 
     
     
         28 . An expression vector comprising a polynucleotide of  claim 27 . 
     
     
         29 . A recombinant cell comprising a polynucleotide of  claim 27 . 
     
     
         30 . (canceled)