Peptide dimers as agonists of the erythropoietin (EPO) receptor, and associated methods of synthesis and use

US7459522B2 · kind B2 · utility

Assignee

• Affymax, Inc. · US

Inventor

• Palani Balu · Cupertino, US

Key dates

• Filing date: Dec 15, 2003
• Grant date: Dec 2, 2008
• Expiry date: Oct 12, 2025

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K38/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Novel peptide dimers are provided that bind and activate the erythropoietin receptor (EPO-R) or otherwise act as an EPO agonist. The novel compounds have a first peptide chain R1 and a second peptide chain R2, wherein R1 and R2 may be the same or different, and are linked through a linking moiety. R1 is approximately 10 to 40 amino acid residues in length and comprises the sequence X3X4X5GPX6TX7X8X9 (SEQ ID NO: 1) wherein X3 is C or Hoc, X4 is R, H, L or W, X5 is M, F, I or nor-leucine (J), X6 is any one of the 20 genetically coded L-amino acids or J, X7 is W, 1-naphthylalanine (B) or 2-naphthylalanine (U), X8 is D, E, I, L or V, and X9 is C or Hoc. Similarly, R2 comprises the sequence X′3X′4X′5GPX′6TX′7X′8X′9 (SEQ IN NO: 2) wherein X′3 is C or Hoc, X′4 is R, H, L or W, X′5 is M, F, I or J, X′6 is any one of the 20 genetically coded L-amino acids or J, X′7 is W, B or U, X8′ is D, E, I, L or V, and X′9 is C or Hoc. Methods for synthesizing the compounds are provided as well, as are pharmaceutical compositions and methods of use.