Peptides capable of binding to serum proteins and compounds, constructs and polypeptides comprising the same

Abstract

The present invention relates to amino acid sequences that are capable of binding to serum proteins; to compounds, proteins, polypeptides, fusion proteins or constructs comprising or essentially consisting of such amino acid sequences; to nucleic acids that encode such amino acid sequences, compounds, proteins, polypeptides, fusion proteins or constructs; to compositions, and in particular pharmaceutical compositions, that comprise such amino acid sequences, compounds, proteins, polypeptides, fusion proteins or constructs; and to uses of such amino acid sequences, compounds, proteins, polypeptides, fusion proteins or constructs.

1 . An isolated amino acid sequence that specifically binds human serum albumin and that comprises:
 (i) an Arg (R) residue that forms a hydrogen bond with the amino acid residues Asn (N) 133 & Asn (N) 135 of human serum albumin and/or forms electrostatic interactions with the main-chain oxygen atoms of the Pro (P) 134 and Leu (L) 136 residues of human serum albumin; and   (ii) a Trp (W) residue that forms electrostatic interactions with the Arg (R) 138 residue of human serum albumin.   
     
     
         2 . The isolated amino acid sequence according to  claim 1 , that comprises:
 (i) a sequence motif RXWD, in which R is arginine, X may be any amino acid, W is tryptophan, and D is aspartic acid; and/or   (ii) a sequence motif GGG, in which G is glycine.   
     
     
         3 . The isolated amino acid sequence according to  claim 2 , wherein in the sequence motif RXWD, X is tryptophan (W), tyrosine (Y), phenylalanine (F), serine (S) or aspartic acid (D). 
     
     
         4 . The isolated amino acid sequence according to  claim 2 , wherein the amino acid sequence comprises sequence motif RXWD and GGG. 
     
     
         5 . The isolated amino acid sequence according to  claim 2 , that comprises:
 (i) the sequence motif RXWD, in which R is arginine, X may be any amino acid, W is tryptophan, and D is aspartic acid; and/or   (ii) a sequence motif FGGG (SEQ ID NO:120), in which F is phenylalanine and G is glycine.   
     
     
         6 . The isolated amino acid sequence according to  claim 5 , wherein in the sequence motif RXWD, X is tryptophan (W), tyrosine (Y), phenylalanine (F), serine (S) or aspartic acid (D). 
     
     
         7 . The isolated amino acid sequence according to  claim 5 , wherein the amino acid sequence comprises sequence motif RXWD and FGGG (SEQ ID NO:120). 
     
     
         8 . The isolated amino acid sequence according to  claim 5 , that comprises
 (i) the sequence motif RXWD, in which R is arginine, X may be any amino acid, W is tryptophan, and D is aspartic acid; and/or   (ii) a sequence motif DVFGGG (SEQ ID NO:129), in which D is aspartic acid, V is valine, F is phenylalanine and G is glycine.   
     
     
         9 . The isolated amino acid sequence according to  claim 8 , wherein in the sequence motif RXWD, X is tryptophan (W), tyrosine (Y), phenylalanine (F), serine (S) or aspartic acid (D). 
     
     
         10 . The isolated amino acid sequence according to  claim 8 , wherein the amino acid sequence comprises sequence motif RXWD and DVFGGG (SEQ ID NO:129). 
     
     
         11 . The isolated amino acid sequence according to  claim 1  that:
 a) has no more than 9 amino acid differences over the full length of the isolated amino acid sequence with the amino acid sequence AASYSDYDVFGGGTDFGP (SEQ ID NO:1); 
 
       and that:
 b) binds better to human serum albumin than the amino acid sequence AASYSDYDVFGGGTDFGP (SEQ ID NO:1). 
 
     
     
         12 . The isolated amino acid sequence according to  claim 11 , in which, compared to the amino acid sequence of SEQ ID NO.1:
 the serine residue (S) at position 3 of SEQ ID NO:1 is replaced by an amino acid residue chosen from arginine (R), proline (P), phenylalanine (F), tyrosine (Y), tryptophan (W), histidine (H), leucine (L), isoleucine (I), valine (V) or methionine (M);   
       and/or
 the serine residue (S) at position 5 of SEQ ID NO:1 is replaced by an amino acid residue chosen from arginine (R), proline (P), phenylalanine (F), tyrosine (Y), tryptophan (W) or histidine (H); 
 
       and/or
 the aspartate residue (D) at position 15 of SEQ ID NO:1 is replaced by an amino acid residue chosen from proline (P), alanine (A), glycine (G), serine (S) or threonine (T); 
 
       and/or
 the phenylalanine residue (F) at position 16 of SEQ ID NO:1 is replaced by proline (P), leucine (L), isoleucine (I), valine (V), methionine (M), alanine (A), glycine (G), serine (S) or threonine (T); 
 
       and/or
 the proline residue (P) at position 18 of SEQ ID NO:1 is maintained or replaced by aspartic acid (D), glutamic acid (E), glutamine (Q), asparagine (N), alanine (A), glycine (G), serine (S) or threonine (T); 
 
       and which amino acid sequence optionally comprises one or more further suitable amino acid insertions, deletions and/or substitutions. 
     
     
         13 . The isolated amino acid sequence according to  claim 11 , that comprises:
 (i) a sequence motif RXWD, in which R is arginine, X may be any amino acid, W is tryptophan, and D is aspartic acid; and/or   (ii) a sequence motif GGG in which G is glycine.   
     
     
         14 . The isolated amino acid sequence according to  claim 5 , wherein in the sequence motif RXWD, X is tryptophan (W), tyrosine (Y), phenylalanine (F), serine (S) or aspartic acid (D). 
     
     
         15 . The isolated amino acid sequence according to  claim 5 , wherein the amino acid sequence comprises sequence motif RXWD and GGG. 
     
     
         16 . The isolated amino acid sequence according to  claim 13 , that comprises:
 (i) the sequence motif RXWD, in which R is arginine, X may be any amino acid, W is tryptophan, and D is aspartic acid; and/or   (ii) a sequence motif FGGG (SEQ ID NO:120) in which F is phenylalanine and G is glycine.   
     
     
         17 . The isolated amino acid sequence according to  claim 16 , wherein in the sequence motif RXWD, X is tryptophan (W), tyrosine (Y), phenylalanine (F), serine (S) or aspartic acid (D). 
     
     
         18 . The isolated amino acid sequence according to  claim 16 , wherein the amino acid sequence comprises sequence motif RXWD and FGGG (SEQ ID NO:120). 
     
     
         19 . The isolated amino acid sequence according to  claim 16 , that comprises
 (i) the sequence motif RXWD, in which R is arginine, X may be any amino acid, W is tryptophan, and D is aspartic acid; and/or   (ii) a sequence motif DVFGGG (SEQ ID NO:129) in which D is aspartic acid, V is valine, F is phenylalanine and G is glycine.   
     
     
         20 . The isolated amino acid sequence according to  claim 19 , wherein in the sequence motif RXWD, X is tryptophan (W), tyrosine (Y), phenylalanine (F), serine (S) or aspartic acid (D). 
     
     
         21 . The isolated amino acid sequence according to  claim 19 , wherein the amino acid sequence comprises sequence motif RXWD and DVFGGG (SEQ ID NO:129). 
     
     
         22 . The isolated amino acid sequence according to  claim 1 , wherein said amino acid sequence is such that, when it is linked or fused to a therapeutic moiety, compound, protein or other therapeutic entity, the compound thus obtained has a longer half-life than a corresponding compound or construct in which said therapeutic moiety, compound, protein or other therapeutic entity is linked or fused to the amino acid sequence of SEQ ID NO:1; and preferably has a half-life that is the same or longer than a corresponding compound or construct in which said therapeutic moiety, compound, protein or other therapeutic entity is linked or fused to the amino acid sequence of SEQ ID NO:14. 
     
     
         23 . The isolated amino acid sequence according to  claim 1 , that is cross-reactive with serum albumin from cynomolgus monkeys ( Macaca fascicularis ). 
     
     
         24 . A compound or construct which comprises at least one amino acid sequence according to  claim 1  and at least one therapeutic moiety. 
     
     
         25 . A compound or construct which comprises at least two amino acid sequences according to  claim 1  and at least one therapeutic moiety. 
     
     
         26 . A compound or construct which comprises at least one tandem repeat comprising at least two amino acid sequences according to  claim 1  and at least one therapeutic moiety.