FC receptor (FcRn) binding peptides and uses thereof

Patent metadata

Field	Value
Publication number	US-10046023-B2
Application number	US-201615354375-A
Country	US
Kind code	B2
Filing date	Nov 17, 2016
Priority date	Jun 18, 2013
Publication date	Aug 14, 2018
Grant date	Aug 14, 2018

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.

First claim

What is claimed is:

1. A method of blocking the interaction between neonatal Fc receptor (FCRN) and albumin in a subject in need thereof, comprising administering to the subject a polypeptide that specifically blocks the interaction between neonatal Fc receptor (FCRN) and albumin;
wherein the polypeptide comprises at least one peptide subunit consisting of an amino acid sequence that is at least 90% identical to RYFCTKWKHGWCEEVGT (SEQ ID NO:1).

2. The method of claim 1 , wherein blocking the interaction between neonatal Fc receptor (FcRn) and albumin decreases albumin level in the subject.

3. The method of claim 1 , wherein the at least one peptide subunit consists of the amino acid sequence set forth in SEQ ID NO:1.

4. The method of claim 1 , wherein the polypeptide comprises two peptide subunits, wherein the peptide subunits consist of an amino acid sequence that is at least 90% identical to SEQ ID NO:1.

5. The method of claim 1 , wherein the polypeptide comprises four peptide subunits, wherein the peptide subunits consist of an amino acid sequence that is at least 90% identical to SEQ ID NO:1.

6. The method of claim 1 , wherein the peptide subunits are linked by a linker.

7. The method of claim 6 , wherein the linker is a peptide linker comprising 1-10 amino acids.

8. The method 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 method 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 method 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 method of claim 1 , wherein blocking the interaction between neonatal Fc receptor (FcRn) and albumin treats toxic exposure to acetaminophen.

Assignees

• Brigham & Womens Hospital Inc
• Biogen Ma Inc

Inventors

• Blumberg Richard S
• Rath Timo
• Baker Kristi
• Mezo Adam
• Taylor Zachary
• Mcdonnell Kevin
• Grenha Rosa Maria Silva Garcia

Classifications

• C07K2319/40

  containing a tag for immunodetection, or an epitope for immunisation · CPC title

• A61K47/54

  the modifying agent being an organic compound · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K14/765

  Serum albumin, e.g. HSA · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title