Peptides and compositions for treatment of joint damage
View Patent ↗The present invention provides new protease resistant polypeptides, as well as compositions and methods for treating, ameliorating or preventing conditions related to joint damage, including acute joint injury and arthritis.
1. An isolated polypeptide comprising an amino acid sequence that has at least 95% amino acid sequence identity to an amino acid sequence selected from the group of sequences of TABLE 1, wherein the polypeptide comprises an amino acid that is a polar amino acid other than K or R at position 423, as determined with reference to SEQ ID NO:1, and wherein the polypeptide has chondrogenic activity.
2. The polypeptide of claim 1 , wherein the polypeptide comprises an amino acid sequence that has at least 95% sequence identity to an amino acid sequence of any one of 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, or SEQ ID NO:41.
3. The polypeptide of claim 1 , wherein the polypeptide comprises an amino acid sequence that has at least 95% sequence identity to an amino acid sequence of any one of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, 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, or SEQ ID NO:29.
4. The polypeptide of claim 1 , wherein the polypeptide comprises an amino acid sequence of any one of 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, or SEQ ID NO:41.
5. The polypeptide of claim 1 , wherein the polypeptide comprises an amino acid sequence of any one of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, or SEQ ID NO:29.
6. The polypeptide of claim 1 , wherein the polypeptide consists of an amino acid sequence that has at least 95% sequence identity to an amino acid sequence of any one of 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, or SEQ ID NO:41.
7. The polypeptide of claim 1 , wherein the polypeptide consists of an amino acid sequence that has at least 95% sequence identity to an amino acid sequence of any one of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, 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, or SEQ ID NO:29.
8. The polypeptide of claim 1 , wherein the polypeptide consists of an amino acid sequence selected from the group of sequences of TABLE 1.
9. The polypeptide of claim 8 , wherein the polypeptide consists of an amino acid sequence selected from any one of 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, or SEQ ID NO:41.
10. The polypeptide of claim 8 , wherein the polypeptide consists of an amino acid sequence selected from any one of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, or SEQ ID NO:29.
11. The polypeptide of any one of claims 1 - 10 , wherein the amino acid at position 423 is Q or S.
12. The polypeptide of any one of claims 1 - 10 , wherein the amino acid at position 423 is Q.
13. The polypeptide of any one of claims 1 - 10 , wherein the amino acid at position 423 is S.
14. The polypeptide of any one of claims 1 - 10 , wherein the polypeptide is PEGylated.
15. The polypeptide of any one of claims 1 - 10 , wherein the polypeptide is fused to a heterologous peptide selected from any of human serum albumin (HSA), an immunoglobulin heavy chain constant region (Fc), a polyhistidine, a glutathione S transferase (GST), a thioredoxin, a protein A, a protein G, or a maltose binding protein (MBP), or a fragment thereof.
16. The polypeptide of any claim 15 , wherein the heterologous peptide is fused at the amino-terminal end of the polypeptide.
17. The polypeptide of claim 15 , wherein the heterologous peptide is fused at the carboxy-terminal end of the polypeptide.
18. A pharmaceutical composition comprising a polypeptide of any one of claims 1 - 10 .
19. The pharmaceutical composition of claim 18 , further comprising a hyaluronic acid or a derivative thereof.
20. The pharmaceutical composition of claim 18 , further comprising an agent selected from the group consisting of oral salmon calcitonin, SD-6010 (iNOS inhibitor), vitamin D3 (choliecalciferol), collagen hydrolyzate, FGF18, BMP7, rusalatide acetate, avocado soy unsaponifiables (ASU), kartogenin, a steroid, and a non-steroidal anti-inflammatory agent (NSAID).
21. A pharmaceutical composition comprising the polypeptide of claim 14 .
22. The pharmaceutical composition of claim 21 , further comprising a hyaluronic acid or a derivative thereof.
23. The pharmaceutical composition of claim 21 , further comprising an agent selected from the group consisting of oral salmon calcitonin, SD-6010 (iNOS inhibitor), vitamin D3 (choliecalciferol), collagen hydrolyzate, FGF18, BMP7, rusalatide acetate, avocado soy unsaponifiables (ASU), kartogenin, a steroid, and a non-steroidal anti-inflammatory agent (NSAID).
24. A pharmaceutical composition comprising the polypeptide of claim 15 .
25. The pharmaceutical composition of claim 24 , further comprising a hyaluronic acid or a derivative thereof.
26. The pharmaceutical composition of claim 24 , further comprising an agent selected from the group consisting of oral salmon calcitonin, SD-6010 (iNOS inhibitor), vitamin D3 (choliecalciferol), collagen hydrolyzate, FGF18, BMP7, rusalatide acetate, avocado soy unsaponifiables (ASU), kartogenin, a steroid, and a non-steroidal anti-inflammatory agent (NSAID).