Dkk2 cysteine rich domain 2 containing proteins and uses thereof
AssigneeBiogen MA Inc.
InventorsR. Blake Pepinsky, Richelle Sopko, Joshua Mugford, Andreas Lehmann, Joseph W. Arndt, Nels E. Pederson, Brenda K. Minesinger
Life of this patent
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Abstract
Proteins containing a DKK2 polypeptide or a fragment or variant thereof are described. These proteins contain human serum albumin sequences and/or include substitutions in the DKK2 polypeptide that decrease heparin binding. These proteins are useful in the treatment of disorders such as acute kidney injury and fibrosis.
Claims46
A polypeptide comprising a first amino acid sequence that is at least 90% identical to amino acids 21-605 of SEQ ID NO:24 that is directly linked or linked via a linker to a second amino acid sequence that is at least 90% identical to amino acids 3-88 of SEQ ID NO:2, wherein the polypeptide binds to LRP5/6.
A polypeptide comprising an amino acid sequence that is at least 90% identical to amino acids 3-88 of SEQ ID NO:2, wherein the amino acid sequence comprises at least one amino acid substitution, relative to SEQ ID NO:2, selected from the group consisting of:
- (a) an amino acid other than arginine at the position corresponding to position 14 of SEQ ID NO:2;
- (b) an amino acid other than arginine at the position corresponding to position 26 of SEQ ID NO:2;
- (c) an amino acid other than lysine at the position corresponding to position 31 of SEQ ID NO:2;
- (d) an amino acid other than lysine at the position corresponding to position 45 of SEQ ID NO:2;
- (e) an amino acid other than lysine at the position corresponding to position 49 of SEQ ID NO:2;
- (f) an amino acid other than histidine at the position corresponding to position 52 of SEQ ID NO:2;
- (g) an amino acid other than lysine at the position corresponding to position 69 of SEQ ID NO:2;
- (h) an amino acid other than lysine at the position corresponding to position 72 of SEQ ID NO:2;
- (i) an amino acid other than serine at the position corresponding to position 77 of SEQ ID NO:2;
- and
- (j) an amino acid other than lysine at the position corresponding to position 79 of SEQ ID NO:2, and
- wherein the polypeptide binds to LRP5/6.
Dependencies are inferred from the claim text.