Peptides and compositions for treatment of joint damage

Abstract

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 . A method of ameliorating arthritis or joint injury in a human patient comprising administering to a joint of the patient an isolated polynucleotide encoding a polypeptide comprising an amino acid sequence that has at least 95% amino acid sequence identity to an amino acid sequence selected from any one of SEQ ID NOs:14-41. 
     
     
         2 . The method of  claim 1 , wherein the isolated polynucleotide is complementary DNA (cDNA) or messenger RNA (mRNA). 
     
     
         3 . The method of  claim 1 , wherein the encoded polypeptide further comprises a secretion signal sequence. 
     
     
         4 . The method of  claim 1 , wherein the encoded polypeptide further comprises a fusion domain selected from the group consisting of a polyhistidine, Glu-Glu, glutathione S transferase (GST), thioredoxin, protein A, protein G, an immunoglobulin heavy chain constant region (Fc), maltose binding protein (MBP), a human serum albumin (HSA), a FLAG tag, influenza virus haemagluttinin (HA), and a c-myc tag. 
     
     
         5 . The method of  claim 1 , wherein the isolated polynucleotide is codon-optimized for expression in a host cell. 
     
     
         6 . The method of  claim 1 , wherein the isolated polynucleotide is operably linked to a promoter or other regulatory sequence. 
     
     
         7 . The method of  claim 1 , wherein expression of the encoded polypeptide ameliorates or prevents arthritis or joint injury in the patient. 
     
     
         8 . A method of ameliorating arthritis or joint injury in a human patient comprising administering to a joint of the patient an expression vector suitable for recombinant expression comprising an isolated polynucleotide encoding a polypeptide comprising an amino acid sequence that has at least 95% amino acid sequence identity to an amino acid sequence selected from any one of SEQ ID NOs:14-41. 
     
     
         9 . The method of  claim 8 , wherein expression of the encoded polypeptide ameliorates or prevents arthritis or joint injury in the patient. 
     
     
         10 . The method of  claim 8 , wherein the isolated polynucleotide is complementary DNA (cDNA) or messenger RNA (mRNA). 
     
     
         11 . The method of  claim 8 , wherein the encoded polypeptide further comprises a secretion signal sequence. 
     
     
         12 . The method of  claim 8 , wherein the encoded polypeptide further comprises a fusion domain selected from the group consisting of a polyhistidine, Glu-Glu, glutathione S transferase (GST), thioredoxin, protein A, protein G, an immunoglobulin heavy chain constant region (Fc), maltose binding protein (MBP), a human serum albumin (HSA), a FLAG tag, influenza virus haemagluttinin (HA), and a c-myc tag. 
     
     
         13 . The method of  claim 8 , wherein the isolated polynucleotide is codon-optimized for expression in a host cell. 
     
     
         14 . The method of  claim 8 , wherein the isolated polynucleotide is operably linked to a promoter or other regulatory sequence. 
     
     
         15 . A kit for use in ameliorating arthritis or joint injury in a human patient comprising the encoded polypeptide as set forth in  claim 1 , wherein the kit comprises: a first container comprising the encoded polypeptide, wherein the encoded polypeptide is in dried form; and a second container having an aqueous reconstitution formula. 
     
     
         16 . The kit according to  claim 15 , wherein one container comprises a single chambered prefilled syringe. 
     
     
         17 . The kit according to  claim 15 , wherein the containers are encompassed as a multichambered pre-filled syringe. 
     
     
         18 . A kit for use in ameliorating arthritis or joint injury in a human patient comprising the expression vector as set forth in  claim 8 , wherein the kit comprises: a first container comprising the encoded polypeptide, wherein the encoded polypeptide is in dried form; and a second container having an aqueous reconstitution formula. 
     
     
         19 . The kit according to  claim 18 , wherein one container comprises a single chambered prefilled syringe. 
     
     
         20 . The kit according to  claim 19 , wherein the containers are encompassed as a multichambered pre-filled syringe.