Muteins of human tear lipocalin capable of binding lymphocyte-activation gene 3 (LAG-3) and methods of use thereof

A mutein of human tear lipocalin that is capable of binding lymphocyte-activation gene 3 (LAG-3),

• wherein the amino acid sequence of the mutein comprises at least 14 of the following mutated amino acid residues in comparison with the linear polypeptide sequence of mature human tear lipocalin (SEQ ID NO:
• 1):
• Ser 14→Pro;
• Asp 25→Ser;
• Arg 26→Ser, Phe, Gly, Ala, Asp or Glu;
• Glu 27→Asp, Val or Thr;
• Phe 28→Cys or Asp;
• Pro 29→Phe, Leu or Trp;
• Glu 30→Trp, Asn or Tyr;
• Met 31→Ile, Val, Asp, Leu or Tyr;
• Asn 32→Asp, Glu, Tyr, Trp, Val, Thr or Met Leu 33→Asp, Glu or Pro;
• Glu 34→Val, Trp or His;
• Val 36→Ala;
• Asn 48→Asp;
• Lys 52→Glu, Ser, Arg or Asn;
• Val 53→Ala;
• Met 55→Ala or Val;
• Leu 56→Asp, Gln or Asn;
• Ile 57→Leu;
• Ser 58→Phe, Trp or Asp;
• Arg 60→Phe or Glu;
• Cys 61→Pro, Leu or Trp;
• Ala 66→Asn;
• Ala 79→Glu;
• Val 85→Ala;
• Ala 86→Asp;
• Cys 101→Ser or Phe;
• Glu 104→Tyr;
• Leu 105→Cys or Gly;
• His 106→Ala, Glu, Thr, Tyr, Gln or Val;
• Lys 108→Tyr, Phe, Thr or Trp;
• Val 110→Gly or Ala;
• Arg 111→Pro;
• Gly 112→Met or Thr;
• Lys 114→Trp or Ala;
• Lys 121→Thr;
• Ser 140→Gly;
• and Cys 153→Ser, and
• wherein the mutein has at least 80% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs:
• 7-22.