Muteins of tear lipocalin and methods for obtaining the same

摘要

The present invention relates to novel muteins derived from human tear lipocalin. The invention also refers to a corresponding nucleic acid molecule encoding such a mutein and to a method for its generation. The invention further refers to a method for producing such a mutein. Finally, the invention is directed to a pharmaceutical composition comprising such a lipocalin mutein as well as to various uses of the mutein.

主权项

1. A mutein of human tear lipocalin having detectable binding affinity to a given non-natural ligand and of human tear lipocalin, wherein at least one of the cysteine residues occurring at sequence positions 61 and 153 of the linear wild type amino acid sequence of mature human tear lipocalin (SEQ ID NO: 71) is replaced by other amino acids and wherein at least 12, 14, or 16 mutated amino acid residues are present at any of the sequence positions 26-34, 56-58, 80, 83, 104-106, and 108 of the linear wild type amino acid sequence of mature human tear lipocalin set forth in SEQ ID NO: 71, wherein the non-natural ligand is vascular endothelial growth factor (VEGF) or a fragment thereof.