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US 9,751,923 B2Granted
Administration of DKK1 muteins to treat fibrosis
AssigneeUniversity of Washington through its Center for Commercialization
InventorsJeremy Duffield, Shuyu Ren, Rashmi Hedge
Life of this patent
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Abstract
The present disclosure provides molecules, compositions and methods for treating scarring in organs. The molecules, compositions and methods treat scarring by modulating the WNT, platelet-derived growth factor receptor (PDGFR), transforming growth factor-beta (TGF3) and/or connective-tissue growth factor (CTGF) signaling pathways.
Claims9
A method of treating scarring of an organ in a subject in need thereof comprising:
- administering an effective amount of a molecule that down-regulates the WNT signaling pathways to the subject in need thereof, wherein the molecule comprises:
- modified SEQ ID NO:5, wherein amino acid residues 28 to 173 of modified SEQ ID NO:5 are at least 90% identical to amino acid residues 28 to 173 of SEQ ID NO:5, and wherein modified SEQ ID NO:5 comprises at least one amino acid modification independently selected from a substitution, a deletion, or an addition, and wherein amino acid residues 174 to 262 of modified SEQ ID NO:5 are identical to amino acid residues 174 to 262 of SEQ ID NO:5;
- modified SEQ ID NO:6, wherein amino acid residues 28 to 53 , 62 to 70, and 87 to 116 of modified SEQ ID NO:6 are at least 90% identical to amino acid residues 28 to 53 , 62 to 70, and 87 to 116 of SEQ ID NO:6, and wherein modified SEQ ID NO:6 comprises at least one amino acid modification independently selected from a substitution, a deletion, or an addition, and wherein amino acid residues 54 to 61 and 71 to 86 of modified SEQ ID NO:6 are identical to amino acid residues 54 to 61 and 71 to 86 of SEQ ID NO:6;
- modified SEQ ID NO:7, wherein amino acid residues 28 to 179 of modified SEQ ID NO:7 are at least 90% identical to amino acid residues 28 to 179 of SEQ ID NO:7, and wherein modified SEQ ID NO:7 comprises at least one amino acid modification independently selected from a substitution, a deletion, or an addition, and wherein amino acid residues 180 to 268 of modified SEQ ID NO:7 are identical to amino acid residues 180 to 268 of SEQ ID NO:7;
- or
- modified SEQ ID NO:8, wherein amino acid residues 28 to 53, 62 to 70, and 87 to 116 of modified SEQ ID NO:8 are at least 90% identical to amino acid residues 28 to 53, 62 to 70, and 87 to 116 of SEQ ID NO:8, and wherein modified SEQ ID NO:8 comprises at least one amino acid modification independently selected from a substitution, a deletion, or an addition, and wherein amino acid residues 54 to 61 and 71 to 86 of modified SEQ ID NO:8 are identical to amino acid residues 54 to 61 and 71 to 86 of SEQ ID NO:8;
- thereby treating scarring of the organ in the subject.
4 more elements
A modified DKK1 protein comprising:
- modified SEQ ID NO:5, wherein amino acid residues 28 to 173 of modified SEQ ID NO:5 are at least 90% identical to amino acid residues 28 to 173 of SEQ ID NO:5, and wherein modified SEQ ID NO:5 comprises at least one amino acid modification independently selected from a substitution, a deletion, or an addition, and wherein amino acid residues 174 to 262 of modified SEQ ID NO:5 are identical to amino acid residues 174 to 262 of SEQ ID NO:5;
- modified SEQ ID NO:6, wherein amino acid residues 28 to 53, 62 to 70, and 87 to 116 of modified SEQ ID NO:6 are at least 90% identical to amino acid residues 28 to 53, 62 to 70, and 87 to 116 of SEQ ID NO:6, and wherein modified SEQ ID NO:6 comprises at least one amino acid modification independently selected from a substitution, a deletion, or an addition, and wherein amino acid residues 54 to 61 and 71 to 86 of modified SEQ ID NO:6 are identical to amino acid residues 54 to 61 and 71 to 86 of SEQ ID NO:6;
- modified SEQ ID NO:7, wherein amino acid residues 28 to 179 of modified SEQ ID NO:7 are at least 90% identical to amino acid residues 28 to 179 of SEQ ID NO:7, and wherein modified SEQ ID NO:7 comprises at least one amino acid modification independently selected from a substitution, a deletion, or an addition, and wherein amino acid residues 180 to 268 of modified SEQ ID NO:7 are identical to amino acid residues 180 to 268 of SEQ ID NO:7;
- or
- modified SEQ ID NO:8, wherein amino acid residues 28 to 53, 62 to 70, and 87 to 116 of modified SEQ ID NO:8 are at least 90% identical to amino acid residues 28 to 53, 62 to 70, and 87 to 116 of SEQ ID NO:8, and wherein modified SEQ ID NO:8 comprises at least one amino acid modification independently selected from a substitution, a deletion, or an addition, and wherein amino acid residues 54 to 61 and 71 to 86 of modified SEQ ID NO:8 are identical to amino acid residues 54 to 61 and 71 to 86 of SEQ ID NO:8.
2 more elements
A method of treating scarring of a peritoneum, a joint, or a large vessel in a subject in need thereof comprising:
- administering an effective amount of a molecule that down-regulates the WNT signaling pathways to the subject in need thereof, wherein the molecule comprises:
- modified SEQ ID NO:5 , wherein amino acid residues 28 to 173 of modified SEQ ID NO:5 are at least 90% identical to amino acid residues 28 to 173 of SEQ ID NO:5, and wherein modified SEQ ID NO:5 comprises at least one amino acid modification independently selected from a substitution, a deletion, or an addition, and wherein amino acid residues 174 to 262 of modified SEQ ID NO:5 are identical to amino acid residues 174 to 262 of SEQ ID NO:5;
- modified SEQ ID NO:6, wherein amino acid residues 28 to 53, 62 to 70, and 87 to 116 of modified SEQ ID NO:6 are at least 90% identical to amino acid residues 28 to 53, 62 to 70, and 87 to 116 of SEQ ID NO:6, and wherein modified SEQ ID NO:6 comprises at least one amino acid modification independently selected from a substitution, a deletion, or an addition, and wherein amino acid residues 54 to 61 and 71 to 86 of modified SEQ ID NO:6 are identical to amino acid residues 54 to 61 and 71 to 86 of SEQ ID NO:6;
- modified SEQ ID NO:7, wherein amino acid residues 28 to 179 of modified SEQ ID NO:7 are at least 90% identical to amino acid residues 28 to 179 of SEQ ID NO:7, and wherein modified SEQ ID NO:7 comprises at least one amino acid modification independently selected from a substitution, a deletion, or an addition, and wherein amino acid residues 180 to 268 of modified SEQ ID NO:7 are identical to amino acid residues 180 to 268 of SEQ ID NO:7;
- or
- modified SEQ ID NO:8, wherein amino acid residues 28 to 53, 62 to 70, and 87 to 116 of modified SEQ ID NO:8 are at least 90% identical to amino acid residues 28 to 53, 62 to 70, and 87 to 116 of SEQ ID NO:8, and wherein modified SEQ ID NO:8 comprises at least one amino acid modification independently selected from a substitution, a deletion, or an addition, and wherein amino acid residues 54 to 61 and 71 to 86 of modified SEQ ID NO:8 are identical to amino acid residues 54 to 61 and 71 to 86 of SEQ ID NO:8;
- thereby treating scarring of the peritoneum, the joint, or the large vessel in the subject.
4 more elements
Dependencies are inferred from the claim text.