Peptides and compositions for treatment of joint damage
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 consisting of: 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: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 64, wherein the amino acid at position 423, as determined with reference to SEQ ID NO: 1, is deleted, and wherein the polypeptide has chondrogenic activity.
2. The polypeptide of claim 1 , wherein the polypeptide comprises an amino acid sequence selected from the group consisting of: 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: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 64.
3. 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 selected from the group consisting of: 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: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 64.
4. The polypeptide of claim 1 , wherein the polypeptide consists of an amino acid sequence selected from the group consisting of: 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: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, and SEQ ID NO: 64.
5. The polypeptide of claim 1 , wherein the polypeptide is PEGylated.
6. The polypeptide of claim 1 , wherein the polypeptide is fused to a heterologous peptide selected from the group consisting of human serum albumin (HAS), immunoglobulin heavy chain constant region (Fc), polyhistidine, glutathione S-transferase (GST), thioredoxin, protein A, protein G, and maltose binding protein (MBP), or a fragment thereof, wherein the heterologous peptide is fused at either the amino-terminal end or the carboxyl-terminal end of the polypeptide.
7. A pharmaceutical composition comprising the polypeptide of claim 1 .
8. The pharmaceutical composition of claim 7 , further comprising an agent selected from the group consisting of hyaluronic acid or a derivative thereof, salmon calcitonin, SD-6010 (iNOS inhibitor), vitamin D3 (choliecalciferol), collagen hydrolyzate, fibroblast growth factor 18 (FGF18), bone morphogenetic protein 7 (BMP7), rusalatide acetate, avocado soy unsaponifiables (ASU), kartogenin, a steroid, and a non-steroidal anti-inflammatory agent (NSAID).