BMP-4 variants with improved properties

Abstract

The invention relates to variants of BMP-4 with improved properties and methods for their use.

1 .- 27 . (canceled) 
     
     
         28 . A non-naturally occurring variant BMP-4 protein comprising at least one substitution as compared to an amino acid sequence comprising SEQ ID NO:2, said substitution selected from the group consisting of: K14R, N15K, R17D, R17E, S20Q, S20R, S20T, S26N, S26Q, N31D, N31S, W33A, W33E, W33N, W33Q, V351, P38K, P38Q, P38R, P38S, P38T, Q41E, Q41A, D48A, D48Q, P50D, P50E, P50R, D55Q, D55T, Q66E, L68E, L68N, L68Q, S71A, S71D, S71R, S71F, V72E, V72K, V72Q, V72T, S74D, S87E, A88D, L92E, L92K, Y93D, Y93E, Y93K, Y93T, L94A, Y97D, Y97N, D98S, D98E, D98N, V100A, V100D, V100R, V100T, L102A, L102E, L102K, L102Q, K103Q, Y105D, Q106D, Q106S, and E111R. 
     
     
         29 . A BMP-4 variant protein of  claim 28 , wherein a substitution is selected from the group consisting of R17D and R17E. 
     
     
         30 . A BMP-4 variant protein of  claim 28 , wherein a substitution is selected from the group consisting of P50D and P50E. 
     
     
         31 . A BMP-4 variant protein of  claim 28 , wherein a substitution is selected from the group consisting of S71A, S71D, S71R and S71F. 
     
     
         32 . A BMP-4 variant protein of  claim 28 , wherein a substitution is selected from the group consisting of Y97D and Y97N. 
     
     
         33 . A nucleic acid encoding the non-naturally occurring variant BMP-4 protein of  claim 28 . 
     
     
         34 . An expression vector comprising the nucleic acid of  claim 33 . 
     
     
         35 . A host cell comprising the nucleic acid of  claim 33 . 
     
     
         36 . A host cell comprising the expression vector of  claim 34 . 
     
     
         37 . A method of producing a non-naturally occurring BMP4 protein comprising culturing the host cell of  claim 35  under conditions suitable for expression of said nucleic acid. 
     
     
         38 . The method according to  claim 37  further comprising recovering said BMP-4 protein. 
     
     
         39 . A pharmaceutical composition comprising the BMP-4 protein of  claim 28 , and a pharmaceutical carrier. 
     
     
         40 . A method for treating a BMP-4 responsive disorder comprising administering the non-naturally occurring BMP-4 protein of  claim 28  to a patient in need of said treatment. 
     
     
         41 . The method according to  claim 40 , wherein said BMP-4 responsive disorder is selected from the group consisting of bone fractures, bone degeneration and spinal fusion.