ELP FUSION PROTEINS COMPRISING PARATHYROID HORMONE FOR CONTROLLED AND SUSTAINED RELEASE
The present disclosure provides novel pharmaceutical compositions comprising a parathyroid hormone or a parathyroid hormone related protein and an elastin-like peptide. These pharmaceutical compositions provide sustained, long-lasting control of serum calcium levels, and may be used in treating osteoporosis and hypoparathyroidism.
1 . A pharmaceutical composition comprising a parathyroid hormone (PTH) or a parathyroid hormone related protein (PTHrP) and an elastin-like peptide, wherein the elastin-like peptide (ELP) comprises repeating units of any one of SEQ ID NOs: 1-13.
2 . The pharmaceutical composition of claim 1 , wherein the PTH is a full-length PTH (SEQ ID NO: 14).
3 . The pharmaceutical composition of claim 1 , wherein the PTH is a truncated PTH.
4 . The pharmaceutical composition of claim 3 , wherein the PTH is truncated at the C-terminus.
5 . The pharmaceutical composition of claim 4 , wherein the PTH is PTH(1-34) (SEQ ID NO: 16) or PTH(1-32) (SEQ ID NO: 18).
6 . The pharmaceutical composition of claim 1 , wherein the PTHrP is a full-length PTHrP.
7 . The pharmaceutical composition of claim 1 , wherein the PTHrP is a truncated PTHrP.
8 . The pharmaceutical composition of claim 7 , wherein the PTHrP is truncated at the C-terminus.
9 . The pharmaceutical composition of claim 8 , wherein the PTHrP is PTHrP (1-32).
10 . The pharmaceutical composition of claim 1 , wherein the ELP comprises structural repeats of SEQ ID NO: 3.
11 . The pharmaceutical composition of claim 10 , wherein X is independently selected from valine, glycine, and alanine.
12 . The pharmaceutical composition of claim 11 , wherein X is independently selected from V, G and A at a ratio of 5:3:2.
13 . The pharmaceutical composition of claim 10 , wherein X is independently selected from valine and alanine.
14 . The pharmaceutical composition of claim 13 , wherein X is independently selected from valine and alanine at a ratio of 6:3.
15 . The pharmaceutical composition of any of claims 1 to 14 , wherein the ELP comprises at least 90 repeating structural units.
16 . The pharmaceutical composition of claim 15 , wherein the ELP comprises at least 120 repeating structural units.
17 . The pharmaceutical composition of claim 16 , wherein the ELP comprises the amino acid sequence of SEQ ID NO: 34.
18 . The pharmaceutical composition of claim 16 , wherein the ELP comprises at least 144 repeating structural units.
19 . The pharmaceutical composition of claim 18 , wherein the ELP comprises the amino acid sequence of SEQ ID NO: 35.
20 . The pharmaceutical composition of any of claims 1 to 18 , wherein the PTH or PTHrP and ELP are in a fusion protein.
21 . The pharmaceutical composition of claim 20 , wherein the fusion protein is selected from:
a) SEQ ID NO: 20;
b) SEQ ID NO: 22;
c) SEQ ID NO: 24;
d) SEQ ID NO: 26;
e) SEQ ID NO: 28; and
f) SEQ ID NO: 30.
22 . A method of increasing serum calcium levels in a subject comprising administering to a subject in need thereof the pharmaceutical composition of any one of claims 1 - 21 .
23 . A method of increasing bone formation in a subject, comprising to a subject in need thereof administering the pharmaceutical composition of any one of claims 1 to 21 .
24 . A method of reducing bone absorption in a subject, comprising administering to a subject in need thereof the pharmaceutical composition of any one of claims 1 to 21 .
25 . A method of treating, ameliorating, or delaying osteoporosis, comprising administering to a subject in need thereof the pharmaceutical composition of any one of claims 1 to 21 .
26 . A method of treating, ameliorating, or delaying hypoparathyroidism, comprising administering to a subject in need thereof the pharmaceutical composition of any one of claims 1 to 21 .
27 . The method of any of claims 22 to 26 , wherein the pharmaceutical composition is administered subcutaneously.
28 . The method of any of claims 22 to 27 , wherein the pharmaceutical composition is administered daily or weekly.