Patent ID: 7541435
Filing Date: 2009-06-02
Classification: A61K,A61P,C07K

Abstract:
1. An isolated polypeptide antagonist of CXCR3-binding CXC chemokines, said antagonist comprising a mutant of CXCL11 in which: a) at least one of the following basic residues, numbered on the sequence of human mature CXCL11, is substituted to Alanine, Glycine, Serine, Threonine, Proline, Glutamic Acid, Glutamine, Aspartic Acid, or Asparagine: 46, 62, or 70; b) at least one of the following basic residues, numbered on the sequence of human mature CXCL11, is substituted to Alanine, Glycine, Serine, Threonine, Proline, Glutamic Acid, Aspartic Acid, or Asparagine: 46, 62, 66 or 70; c) at least one of the following basic residues, numbered on the sequence of human mature CXCL11, is substituted to Alanine, Glycine, Serine, Threonine, Proline, Glutamic Acid, Glutamine, Aspartic Acid, or Asparagine: 46, 62, 66, or 70 and at least one of the following basic residues, numbered on the sequence of human mature CXCL11, is additionally substituted to Alanine, Glycine, Serine, Threonine, Proline, Glutamic Acid, Glutamine, Aspartic Acid, or Asparagine: 49, 52, 57, 59, or 71; d) at least one of the following basic residues, numbered on the sequence of human mature CXCL11, is substituted to Alanine, Glycine, Serine, Threonine, Proline, Glutamic Acid, Glutamine, Aspartic Acid, or Asparagine: 46, 62, 66, or 70 and at least one of the following basic residues, numbered on the sequence of human mature CXCL11, is additionally substituted to Glycine, Serine, Threonine, Proline, Glutamic Acid, Glutamine, Aspartic Acid, or Asparagine: 49, 52, 57, 59, 67 or 71; e) one of the following combinations of basic residues, numbered on the sequence of human mature CXCL11, is substituted to Alanine, Glycine, Serine, Threonine, Proline, Glutamic Acid, Glutamine, Aspartic Acid, or Asparagine: f) at least one of the following basic residues, numbered on the sequence of human mature CXCL11, of an antagonist set forth in a), b), c) or d) is additionally substituted to Alanine, Glycine, Serine, Threonine, Proline, Glutamic Acid, Glutamine, Aspartic Acid, or Asparagine: 5, 6, 8, 17, 20, 26 or 38; g) the basic residues of an antagonist as set forth in a), b), c), d), e) or f) are substituted with Alanine or Glycine; h) said antagonist comprises CXCL11-2B3 (SEQ ID NO: 3), CXCL11-3B3 (SEQ ID NO: 4), or CXCL11-4B4 (SEQ ID NO: 5); or i) one or more of the first nine amino acids in the amino-terminal domain of the human mature CXCR3-binding CXC chemokine have been added, deleted, or substituted in an antagonist as set forth in a), b), c), d), e), f), g) or h).