COMPOUNDS, COMPOSITIONS AND USES THEREOF FOR IMPROVEMENT OF BONE DISORDERS
The present technology generally relates to peptides of IGFBP-2 that may be used to improve bone disorders. The present technology also generally relates to uses of such peptides in methods for preventing or treating bone disorders and to compositions for such uses.
1 . An isolated peptide consisting of a fragment of heparin binding domain (HBD) as set forth in SEQ ID NO: 1, said fragment being 6 to 9 amino acids in length and comprising an amino acid sequence GLEEPK as set forth in SEQ ID NO: 14 or an analog thereof.
2 . (canceled)
3 . The isolated peptide as defined in claim 1 , wherein the HBD is HBD1.
4 . The isolated peptide as defined in claim 1 , wherein the isolated peptide is modified.
5 . The isolated peptide as defined in claim 4 , wherein the modification is performed in vitro.
6 . The isolated peptide as defined in claim 4 , wherein the modification is a post-translational modification.
7 . The isolated peptide as defined in claim 6 , wherein the post-translational modification is a pegylation.
8 . The isolated peptide as defined in claim 7 , wherein the isolated peptide is coupled to one or more pegylation (PEG) group.
9 . The isolated peptide as defined in claim 8 , wherein the one or more PEG group is at the N-terminus of the isolated peptide.
10 . The isolated peptide as defined in claim 8 , wherein the one or more PEG group is at the C-terminus of the isolated peptide.
11 . The isolated peptide as defined in claim 6 , wherein the post-translational modification is acylation.
12 . The isolated peptide as defined in claim 11 , wherein the isolated peptide is coupled to one or more acyl group.
13 . The isolated peptide as defined in claim 12 , wherein the one or more acyl group is at the N-terminus of the isolated peptide.
14 . The isolated peptide as defined in claim 12 , wherein the one or more acyl group is at the C-terminus of the isolated peptide.
15 . The isolated peptide as defined in claim 11 , wherein the acylation is a fatty acylation.
16 . The isolated peptide as defined in claim 15 , wherein the fatty acylation is by coupling one or more of a lauric acid (C12:0), tridecyclic acid (C13:0), myristic acid (C14:0), pentadecyclic acid (C15:0), palmitic acid (C16:0), margaric acid (C17:0), stearic acid (C18:0), nonadecyclic acid (C19:0), arachidinic acid (C20:0), heneicosylic acid (C21:0), behenic acid (C22:0), tricosylic acid (C23:0), and lignoceric acid (C24:0) to the isolated peptide.
17 .- 20 . (canceled)
21 . The isolated peptide as defined in claim 1 , wherein the isolated peptide is cyclic.
22 . The isolated peptide as defined in claim 1 , wherein the fragment is as set forth in SEQ ID NO: 14 or is an analog thereof.
23 . The isolated peptide as defined in claim 1 , wherein the fragment is as set forth in SEQ ID NO: 10 or is an analog thereof.
24 . (canceled)
25 . The isolated peptide as defined in claim 1 , wherein the fragment is as set forth in SEQ ID NO: 77 or is an analog thereof.
26 .- 30 . (canceled)
31 . An isolated peptide consisting of an amino acid sequence selected from: SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113 and any analog thereof.
32 .- 34 . (canceled)
35 . An isolated peptide consisting of an amino acid sequence as set forth in SEQ ID NO: 73 or an analog thereof.
36 .- 62 . (canceled)
63 . A method for prevention or treatment of a bone disorder in a subject in need thereof, the method comprising administering the isolated peptide as defined in claim 1 to the subject in an amount effective to prevent or treat the bone disorder in the subject.
64 . The method as defined in claim 63 , wherein the bone disorder is selected from: osteoporosis, osteopenia, osteogenesis imperfecta, osteonecrosis, low bone mass, Paget's disease, osseous metastasis, aseptic prosthetic loosening, periodontitis, metastatic bone disease, rheumatoid arthritis, lupus arthritis, periodontal disease, alveolar bone loss, post-osteotomy, childhood idiopathic bone loss, curvature of the spine, loss of height, and prosthetic surgery.
65 . The method as defined in claim 63 , wherein the bone disorder is selected from: osteopathy in acromegalic patients, cystic fibrosis-related bone disease, adynamic bone disease, renal osteodystrophy associated with chronic kidney disease, bone disease associated with cystinosis, and bone disease associated with hyperoxaluria.
66 . The method as defined in claim 63 , wherein the bone disorder is selected from: a broken bone, a bone defect, a bone transplant, a bone graft, a bone cancer, a joint replacement, a joint repair, a fusion, a facet repair, a bone degeneration, a dental implant, a dental repair, a bone marrow deficit and any combination thereof.
67 .- 83 . (canceled)