US2016185842A1PendingUtilityA1

14-3-3 Antagonists for the Prevention and Treatment of Arthritis

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Assignee: UNIV BRITISH COLUMBIAPriority: Nov 27, 2007Filed: Oct 1, 2015Published: Jun 30, 2016
Est. expiryNov 27, 2027(~1.3 yrs left)· nominal 20-yr term from priority
Inventors:Anthony MarottaAziz GhaharyWalter Wolodymyr Peter MaksymowychRuhangiz Taghi Kilani
A61P 37/06A61P 43/00A61P 29/00A61P 19/02G01N 2333/47A61K 2039/505G01N 33/6893G01N 2800/102C07K 2317/24C07K 2317/76G01N 33/53C07K 2317/33C07K 2317/34C07K 16/18A61K 39/395A61K 39/001163A61K 39/001162A61K 2039/515G01N 33/564
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Claims

Abstract

The invention provides compositions and methods for treating arthritis.

Claims

exact text as granted — not AI-modified
1 . A method for treating arthritis, comprising administering to a patient a therapeutically effective amount of a 14-3-3 antagonist, wherein said 14-3-3 antagonist is capable of specifically binding to an extracellularly localized 14-3-3 protein, wherein said 14-3-3 protein is selected from γ and η isoforms. 
     
     
         2 . The method according to  claim 1 , wherein said 14-3-3 antagonist is a peptide. 
     
     
         3 . The method according to  claim 2 , wherein said peptide comprises the amino acid sequence of R-18. 
     
     
         4 . The method according to  claim 2 , wherein said peptide consists essentially of the amino acid sequence of R-18. 
     
     
         5 . The method according to  claim 2 , wherein said peptide comprises a segment of the amino acid sequence of R-18. 
     
     
         6 . The method according to  claim 1 , wherein said 14-3-3 antagonist is an anti-14-3-3 antibody. 
     
     
         7 . The method according to  claim 6 , wherein said antibody is a monoclonal antibody. 
     
     
         8 . The method according to  claim 7 , wherein said monoclonal antibody is a humanized monoclonal antibody. 
     
     
         9 . The method according to  claim 6 , wherein said anti-14-3-3 antibody is an anti-14-3-3 eta antibody. 
     
     
         10 . The method according to  claim 9 , wherein said anti-14-3-3 eta antibody is a pan 14-3-3 antibody. 
     
     
         11 . The method according to  claim 9 , wherein said anti-14-3-3 eta antibody is capable of discriminating between 14-3-3 protein isoforms. 
     
     
         12 . The method according to  claim 9 , wherein said anti-14-3-3 eta antibody is capable of specifically binding to a loop, helix, or non-helix 14-3-3 eta peptide. 
     
     
         13 . The method according to  claim 9 , wherein said anti-14-3-3 eta antibody is capable of binding to an amino acid sequence selected from the group consisting of SEQ ID NOs:1-32. 
     
     
         14 . The method according to  claim 9 , wherein said anti-14-3-3 eta antibody is capable of specifically binding to the amino acid sequence LDKFLIKNSNDF (SEQ ID NO:30). 
     
     
         15 . The method according to  claim 9 , wherein said anti-14-3-3 eta antibody is capable of specifically binding to the amino acid sequence KKLEKVKAYR (SEQ ID NO:31). 
     
     
         16 . The method according to  claim 9 , wherein said anti-14-3-3 eta antibody is capable of specifically binding to the amino acid sequence KNSVVEASEAAYKEA (SEQ ID NO:32). 
     
     
         17 . The method according to  claim 6 , wherein said anti-14-3-3 antibody is an anti-14-3-3 gamma antibody. 
     
     
         18 . The method according to  claim 17 , wherein said anti-14-3-3 gamma antibody is a pan 14-3-3 antibody. 
     
     
         19 . The method according to  claim 17 , wherein said anti-14-3-3 gamma antibody is capable of differentiating between 14-3-3 protein isoforms. 
     
     
         20 . The method according to  claim 17 , wherein said anti-14-3-3 gamma antibody is capable of specifically binding to a loop, helix, or non-helix 14-3-3 gamma peptide. 
     
     
         21 . The method according to  claim 17 , wherein said anti-14-3-3 gamma antibody is capable of binding to an amino acid sequence selected from the group consisting of SEQ ID NOs:33-62. 
     
     
         22 - 71 . (canceled) 
     
     
         72 . A method for reducing MMP expression in the synovium of a patient, comprising administering to a patient a therapeutically effective amount of a 14-3-3 antagonist, wherein said 14-3-3 antagonist is capable of specifically binding to an extracellularly localized 14-3-3 protein, wherein said 14-3-3 protein is selected from γ and η isoforms. 
     
     
         73 . The method according to  claim 72 , wherein said MMP is selected from the group consisting of MMP-1, 3, 8, 9, 10, 11 and 13. 
     
     
         74 . The method according to  claim 73 , wherein said MMP is MMP-1 or MMP-3, 
     
     
         75 - 80 . (canceled) 
     
     
         81 . A method of prophylactically treating arthritis in an individual in need thereof comprising selecting an individual suspected of having, predisposed to, or at risk of developing arthritis and administering a therapeutically effective amount of a 14-3-3 antagonist to the individual in need thereof, wherein said 14-3-3 antagonist is capable of specifically binding to an extracellularly localized 14-3-3 protein, and wherein said 14-3-3 protein is selected from γ and η isoforms. 
     
     
         82 . A method of reducing the severity of arthritis in an individual in need thereof, comprising selecting an individual suffering from arthritis and administering to a patient a therapeutically effective amount of a 14-3-3 antagonist, wherein said 14-3-3 antagonist is capable of specifically binding to an extracellularly localized 14-3-3 protein, wherein said 14-3-3 protein is selected from γ and η isoforms.

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