Recombinant protein variants

Abstract

The present invention relates to novel recombinant protein variants that are useful as immunotherapeutic components. Also the present invention relates to DNA sequences encoding said protein variants as well as compositions comprising said protein variants.

1 - 17 . (canceled) 
     
     
         18 . A method of producing a recombinant protein variant with the ability to induce a protective immune response to a naturally occurring allergen, comprising the steps of:
 selecting a scaffold protein, said scaffold protein having a three-dimensional folding pattern that is structurally similar to that of the naturally occurring allergen,   introducing two or more primary mutations, that are spaced by at least one non-mutated amino acid residue, into the scaffold protein, each primary mutation introducing into the scaffold protein at least one amino acid residue identical or homologous to the corresponding amino acid residue or residues in the naturally occurring allergen, and   the protein variant having, compared to the scaffold protein, an increased affinity and/or binding capacity to IgE antibodies that are specific to the naturally occurring protein.   
     
     
         19 . A protein variant obtainable by the process of  claim 18 . 
     
     
         20 . A protein variant according to  claim 18 , wherein the naturally occurring allergen is an inhalation allergen. 
     
     
         21 - 34 . (canceled) 
     
     
         35 . A protein variant according to  claim 20 , wherein the naturally occurring allergen is a house dust mite allergen. 
     
     
         36 . A protein variant according to  claim 35 , wherein the naturally occurring allergen is a mite allergen originating from  Dermatophagoides.    
     
     
         37 . A protein variant according to  claim 36 , wherein the naturally occurring allergen is Der p 2. 
     
     
         38 . A protein variant according to  claim 37 , wherein the scaffold protein is Eur m 1. 
     
     
         39 . A protein variant according to  claim 37 , wherein the scaffold protein is Lep d 2. 
     
     
         40 . A protein variant according to  claim 39  that comprises at least two primary mutations selected from the group consisting of: D17L, D17I, D17V, D17M, S19P, Q32K, Q32R, Q32H, K33P, T35Q, T35N, N88K, N88R, N88H, T92N, T92Q, A95K, A95R, A95H and optionally one or more secondary mutations selected from the group consisting of: K6X, S22X, R30X, K76S, K81X, V114X. 
     
     
         41 . A protein variant according to  claim 39  that comprises at least two primary mutations selected from the group consisting of: D45N, D45Q, N47K, N47R, N47H, K48T, K48S, T50K, T50R, T50H, K52E, K52D, L54K, L54R, L54H, E107K, E107R, E107M, H112D, H112E, T119I, T119L, T119V, T199M and Optionally One or More Secondary Mutations Selected from the Group consisting of: K6X, S22X, K29X, R30X, K76X, K81X. 
     
     
         42 . A protein variant according to  claim 37  wherein the scaffold protein is Gly d 2. 
     
     
         43 . A protein variant according to  claim 42  that comprises at least two primary mutations selected from the group consisting of: K2Q, K2N, K4D, K4E, K10N, K10Q, T14K, T14R, S22H, S22R, S22K, K39V, K39L, K39I, K39M. D45N, D45Q, T60L, T60V, T60I, T60M, Q63D, Q63E, K80V, K80L, K80I, K80M, T91S, H112D, H112E, R122I, R122V, R122L, R122M and optionally one or more secondary mutations selected from the group consisting of: K6X, preferably K6R or K6H, R30X, preferably R30K or R30H, F74X, preferably F74Y or, F74W, K81X, preferably K81R or K81H, K88X, preferably K88R or K88H, T90X, and V114X, preferably V114L, V114I or V114M. 
     
     
         44 - 75 . (canceled)