Human tear lipocalins which bind PCSK9 and methods of use thereof

摘要

The present disclosure relates to novel lipocalin muteins which bind to PCSK9. The disclosure also provides corresponding nucleic acid molecules encoding lipocalin muteins and methods for producing lipocalin muteins as well as their encoding nucleic acid molecules.

主权项

1. A mutein of human tear lipocalin, wherein the mutein comprises:
(a) a mutated amino acid residue at any one or more of the sequence positions 26-34, 56-58, 80, 83, 104-106 and 108 of the linear polypeptide sequence of the mature human tear lipocalin, wherein the mutein comprises at least one of the following amino acid substitutions in comparison to mature human tear lipocalin: (i) Arg 26→Ser, Phe, Trp, His or Thr and (ii) Glu 34→Asn, Thr, Arg or Gly; and (b) a mutated amino acid residue at any one or more of the sequence positions 61, 101, 111, 114 and 153 of the linear polypeptide sequence of the mature human tear lipocalin, and wherein the mutein binds specifically to proprotein convertase subtilisin/kexin type 9 (PCSK9).