FC RECEPTOR (FcRn) BINDING PEPTIDES AND USES THEREOF

Abstract

The invention provided herein includes isolated polypeptides that specifically block the interaction between neonatal Fc receptor (FcRn) and albumin. Blocking the interaction treats diseases and conditions caused by increased amounts of albumin or modified albumin that possesses pathogenic properties wherein it is deemed desirable to decrease albumin levels. Accordingly, also provided are methods of using these isolated polypeptides to treat various diseases and conditions caused by increased amounts of albumin or modified albumin that possesses pathogenic properties. The invention provided herein also includes isolated polypeptides capable of binding to a non-IgG and non-albumin competitive site on an FcRn alpha 3 domain. These can be useful for tracking FcRn without inhibiting IgG or albumin binding or function. Accordingly, the invention also includes methods and systems to track FcRn without inhibiting IgG or albumin binding or function.

1 . An isolated polypeptide that specifically blocks the interaction between neonatal Fc receptor (FCRN) and albumin comprising at least one peptide subunit consisting of an amino acid sequence X 1 —Y—X 2 —C—X 3 —X 4 —W—X 5 —X 6 —X 7 —W—C—X 8 —X 9 —V—X 10 —X 11  (SEQ ID NO:7), wherein X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , and X 11  is each independently selected from any amino acid, or is deleted. 
     
     
         2 . The isolated polypeptide of  claim 1 , wherein
 X 1  is R or a conservative amino acid substitution of R,   X 2  is F or a conservative amino acid substitution of F,   X 3  is T or a conservative amino acid substitution of T,   X 4  is K or a conservative amino acid substitution of K,   X 5  is K or a conservative amino acid substitution of K,   X 6  is H or a conservative amino acid substitution of H,   X 7  is G or a conservative amino acid substitution of G,   X 8  is E or a conservative amino acid substitution of E,   X 9  is E or a conservative amino acid substitution of E,   X 10  is G, a conservative amino acid substitution of G, or is deleted, and   X 11  is T, a conservative amino acid substitution of T, or is deleted (an embodiment disclosed as SEQ ID NO: 124).   
     
     
         3 . The isolated polypeptide of  claim 1 , wherein, X 1  is R, X 2  is F, X 7  is G, and/or X 10  is E (embodiments disclosed as SEQ ID NOS 12-13). 
     
     
         4 . The isolated polypeptide of  claim 1 , comprising two peptide subunits. 
     
     
         5 . The isolated polypeptide of  claim 1 , comprising four peptide subunits. 
     
     
         6 . The isolated polypeptide of  claim 4 , wherein the peptide subunits are linked by a linker. 
     
     
         7 . The isolated polypeptide of  claim 6 , wherein the linker is a peptide linker comprising 1-10 amino acids. 
     
     
         8 . The isolated polypeptide of  claim 6 , wherein the linker is a glycine linker comprising 1-10 glycine residues (SEQ ID NO: 14), or 1-10 glycine and serine residues (SEQ ID NO: 15). 
     
     
         9 . The isolated polypeptide of  claim 8 , wherein the glycine linker comprises 3-5 glycine residues (SEQ ID NO: 16), or 3-5 glycine and serine residues (SEQ ID NO: 17). 
     
     
         10 . The isolated polypeptide of  claim 6 , wherein the linker is formed from a polyethylene glycol (PEG) H(O—CH 2 —CH 2 ) n —OH, wherein n is an integer from 2-12. 
     
     
         11 . The isolated polypeptide of  claim 1 , wherein the peptide subunit is a cyclic peptide. 
     
     
         12 . The isolated polypeptide of  claim 1  comprising at least one amino acid analog or amino acid mimetic. 
     
     
         13 . The isolated polypeptide of  claim 1  comprising a modified peptide backbone. 
     
     
         14 . The isolated polypeptide of  claim 1  comprising a hydrophilic unstructured polymer. 
     
     
         15 . The isolated polypeptide of  claim 14 , wherein the hydrophilic unstructured polymer is an extended recombinant polypeptide. 
     
     
         16 . The isolated polypeptide of  claim 1  comprising polyethylene glycol (PEG). 
     
     
         17 . The isolated polypeptide of  claim 1 , wherein the polypeptide is acetylated. 
     
     
         18 . The isolated polypeptide of  claim 1 , further comprising at least one second protein or peptide to form a fusion peptide. 
     
     
         19 . The isolated polypeptide of  claim 18 , wherein the at least second peptide or protein comprises an epitope tag or a half-life extender or both. 
     
     
         20 .- 25 . (canceled) 
     
     
         26 . A method of blocking the interaction between neonatal Fc receptor (FCRN) and albumin in a subject in need thereof, comprising administering the polypeptide of  claim 1  to the subject. 
     
     
         27 .- 43 . (canceled)