Muteins with tear lipocalin having affinity to human c-met receptor tyrosine kinase and methods for obtaining the same
The present invention relates to novel muteins derived from human tear lipocalin having affinity to human c-Met receptor tyrosin kinase (c-Met). 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.
1. A nucleic acid molecule comprising a nucleotide sequence encoding a mutein of human tear lipocalin (hTLc) having detectable binding affinity to human Met receptor tyrosine kinase (c-Met) or a domain or fragment thereof and wherein said mutein comprises at least 8 amino acid substitutions with respect to the amino acid sequence of mature human tear lipocalin (SEQ ID NO:36), which are selected from the group consisting of Arg 26→Thr, Val, Pro, Ser, or Gly; Glu 27→Gln, Gly, Val, or Ser; Phe 28→Met, or Asp; Pro 29→Leu, Ile, Ala, or Trp; Glu 30→Leu, Gly, Arg, or Phe; Met 31→Ser; Asn 32→Leu, Arg, Val, or Gln; Leu 33→Tyr, Val, Ile, Thr, or Phe; Glu 34→Val, Arg, or Ala; Leu 56→Asn; Ile 57→Gln; Ser 58→Ile, or Val; Asp 80→Tyr; Lys 83→Ala; Glu 104→Asp; Leu 105→Thr; His 106→Trp; and Lys 108→Gly.
2. A host cell comprising a nucleic acid molecule of claim 1 .