Fusion protein

Abstract

The present invention relates to a p75NTR neurotrophin binding protein (NBP)-Fc fusion protein comprising a p75NTR(NBP) portion and an immunoglobulin portion. In certain embodiments, the p75NTR(NBP)-Fc fusion protein is for use in the treatment of pain and/or a symptom of pain.

1 . A p75NTR neurotrophin binding protein (NBP)-Fc fusion protein, comprising:
 (a) a p75NTR(NBP) portion; and   (b) an immunoglobulin Fc portion.   
     
     
         2 . The p75NTR(NBP)-Fc fusion protein according to  claim 1 , wherein the p75NTR(NBP) and Fc portions are connected via a linker. 
     
     
         3 . The p75NTR(NBP)-Fc fusion protein according to  claim 2 , wherein the linker comprises a peptide of formula G x , where x is 1, 2, 3, 4, 5 or 6. 
     
     
         4 . The p75NTR(NBP)-Fc fusion protein according to any one of  claims 1  to  3 , wherein the p75NTR(NBP) is a human p75NTR(NBP). 
     
     
         5 . The p75NTR(NBP)-Fc fusion protein according to any one of  claims 1  to  4 , wherein the Fc is a human Fc. 
     
     
         6 . The p75NTR(NBP)-Fc fusion protein according to any preceding claim, comprising or consisting of the amino acid sequence set forth in SEQ ID NO:3. 
     
     
         7 . The p75NTR(NBP)-Fc fusion protein according to any one of  claims 1  to  5 , comprising or consisting of the amino acid sequence set forth in SEQ ID NO:15. 
     
     
         8 . The p75NTR(NBP)-Fc fusion protein according to any preceding claim wherein the p75NTR(NBP) binds to any of NGF, BDNF, NT3 or NT4/5 with a binding affinity (K d ) of between about 0.01 nM to about 50 nM as measured by surface plasmon resonance at 20° C. 
     
     
         9 . The p75NTR(NBP)-Fc fusion protein according to any preceding claim for use in the treatment of pain or a symptom of pain. 
     
     
         10 . A nucleic acid molecule encoding the p75NTR(NBP)-Fc fusion protein according to any one of  claims 1  to  8 , optionally further comprising encoding a signal sequence. 
     
     
         11 . A replicable expression vector for transfecting a cell, optionally a mammalian cell, the vector comprising the nucleic acid molecule of  claim 10 . 
     
     
         12 . The replicable expression vector of  claim 11  wherein the vector is a viral vector. 
     
     
         13 . A host cell harbouring the nucleic acid molecule of  claim 10 . 
     
     
         14 . The nucleic acid molecule according to  claim 10  or the vector according to either of  claim 11  or  12  for use in the treatment of pain or a symptom of pain. 
     
     
         15 . The p75NTR(NBP)-Fc fusion protein according to any one of  claims 1  to  8  or  claim 9  or the nucleic acid or vector according to any one of  claims 10  to  14 , wherein the p75NTR(NBP)-Fc fusion protein or nucleic acid molecule or vector is for separate, sequential or simultaneous use in a combination combined with a second pharmacologically active compound. 
     
     
         16 . A pharmaceutical composition, comprising the p75NTR(NBP)-Fc fusion protein according to any one of  claims 1  to  8  or  claim 9  or the nucleic acid molecule or vector according to  claims 11  to  14 , and a pharmaceutically acceptable carrier and/or an excipient. 
     
     
         17 . A kit comprising:
 (a) the p75NTR(NBP)-Fc fusion protein according to any one of  claims 1  to  8  or  claim 9  or the nucleic acid molecule or vector according to  claims 10  to  14 ; and   (b) instructions for the administration of an effective amount of said the p75NTR(NBP)-Fc fusion protein, nucleic acid molecule, vector or pharmaceutical composition to an individual for any one or more of the prevention or treatment of pain and/or a symptom of pain or for ameliorating, controlling, reducing incidence of, or delaying the development or progression of pain and/or a symptom of pain.   
     
     
         18 . A method of treating and or preventing pain and or a symptom of pain in an individual comprising administering to said individual a therapeutically effective amount of the p75NTR(NBP)-Fc fusion protein according to any one of  claims 1  to  8  or  claim 9  or the nucleic acid molecule or vector according to  claims 10  to  14 , optionally further comprising a pharmaceutically acceptable carrier.