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.

What is claimed is: 
     
         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: 58-70, wherein the amino acid at position 423, as determined with reference to SEQ ID NO:1, is deleted, whereupon expression of the encoded polypeptide ameliorates or prevents arthritis or joint injury in the patient. 
     
     
         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 haemagglutinin (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 . A method of ameliorating arthritis or joint injury in a human patient, comprising: administering to a joint of the patient an expression vector comprising a 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: 58-70, wherein the amino acid at position 423, as determined with reference to SEQ ID NO:1, is deleted, whereupon expression of the encoded polypeptide ameliorates or prevents arthritis or joint injury in the patient. 
     
     
         8 . A kit 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: 58-70, wherein the amino acid at position 423, as determined with reference to SEQ ID NO:1, is deleted, wherein the kit comprises a first container comprising the encoded polypeptide, and a second container having an aqueous reconstitution formula. 
     
     
         9 . The kit according to  claim 8 , wherein the encoded polypeptide in the first container is in dry form. 
     
     
         10 . The kit according to  claim 8 , wherein one container comprises a single chambered pre-filled syringe. 
     
     
         11 . The kit according to  claim 8 , wherein the containers are encompassed as a multi-chambered pre-filled syringe.