Modified ciliary neurotrophic factors

Abstract

Modified ciliary neurotrophic factors and methods for their production and therapeutic use. Also described is a method of screening for novel therapeutic proteins by determining altered electrophoretic binding properties.

We claim:  
     
         1 . A human ciliary neurotrophic factor (CNTF) protein (SEQ ID NO:1) in which glutamine at position 63 (Q63) is substituted by arginine and cysteine at position 17 (C17) is substituted with another amino acid.  
     
     
         2 . The protein of  claim 1 , wherein C17 is substituted by serine or alanine.  
     
     
         3 . A human ciliary neurotrophic factor (CNTF) protein (SEQ ID NO:1) in which glutamine at position 63 (Q63) is substituted by another amino acid.  
     
     
         4 . The protein of  claim 3 , wherein Q63 is substituted by alanine, asparagine, histidine, glutamic acid, or lysine.  
     
     
         5 . The protein of  claim 3 , further modified by a substitution of cysteine at position 17 (C17).  
     
     
         6 . The protein of  claim 3  further modified to reduce immunogenicity.  
     
     
         7 . The protein of  claim 6 , wherein the modification is a truncation of the C-terminus.  
     
     
         8 . The protein of  claim 7 , wherein the truncation is 13 or 15 amino acids.  
     
     
         9 . The protein of  claim 6 , further modified by a substitution of tryptophan at position 64 (W64).  
     
     
         10 . The protein of  claim 5 , further modified by a substitution of tryptophan at position 64 (W64).  
     
     
         11 . The protein of  claim 5 , wherein the substitution at C17 is serine or alanine.  
     
     
         12 . The protein of  claim 5 , further modified to reduce immunogenicity.  
     
     
         13 . The protein of  claim 12 , wherein the modification is a truncation of the C-terminus.  
     
     
         14 . The protein of  claim 13 , wherein the truncation if 13 or 15 amino acids.  
     
     
         15 . The protein of  claim 12 , further modified by a substitution of tryptophan at position 64 (W64).  
     
     
         16 . A human ciliary neurotrophic factor (CNTF) protein (SEQ ID NO:1) which is modified by a substitution of glutamine at position 63 (Q63), and a substitution of tryptophan at position 64 (W64).  
     
     
         17 . The protein of  claim 16 , where in the substitution of Q63 is arginine, alanine, asparagine, histidine, glutamic acid, or lysine.  
     
     
         18 . The protein of  claim 16 , where in the substitution of W64 is alanine, phenylalanine, histidine, or glutamine.  
     
     
         19 . The protein of  claim 16 , where in the substitution of Q63 is arginine and the substitution of W64 is alanine.  
     
     
         20 . A human ciliary neurotrophic factor (CNTF) protein (SEQ ID NO:1) which is modified by a substitution of glutamine at position 63 (Q63) with alanine, asparagine, histidine, glutamic acid, or lysine, and a substitution of tryptophan at position 64 (W64) with phenylalanine, histidine, or glutamine.  
     
     
         21 . The protein of  claim 20 , further modified to reduce immunogenicity.  
     
     
         22 . The protein of  claim 21 , wherein the modification is a truncation of the C-terminus.  
     
     
         23 . The protein of  claim 22  wherein the truncation is 13 or 15 amino acids.