Fusion constructs containing active sections of tnf ligands

Abstract

Disclosed is a recombinant fusion protein containing an amino-acid sequence which comprises: (a) the Fc section or part of an Fc section of an immunoglobulin as component (A) or a functional variant of component (A); (b) the extracellular part of a TNF ligand or a partial sequence of the extracellular part of a TNF ligand as component (B) or a functional variant of component (B); and optionally (c) a transition area between component (A) and component (B), containing a linker.

1 . A recombinant fusion protein which contains an amino acid sequence which comprises: (a) an Fc segment of an immunoglobulin, wherein the Fc segment consists of amino acids 18 to 243 of SEQ ID NO: 8, as component (A), and (b) an extracellular moiety of EDA2, as component (B), wherein component (B) comprises amino acids 266 to 410 of SEQ ID NO: 8. 
     
     
         2 . The recombinant fusion protein of  claim 1 , wherein the recombinant fusion protein has the amino acid sequence of SEQ ID NO: 8. 
     
     
         3 . A pharmaceutical composition comprising the recombinant fusion protein of  claim 1 , and a pharmaceutically acceptable carrier material. 
     
     
         4 . A nucleic acid sequence, encoding the recombinant fusion protein of  claim 1 . 
     
     
         5 . An expression vector, wherein the expression vector contains the nucleic acid sequence of  claim 4 . 
     
     
         6 . An isolated host cell transfected with the expression vector as claimed in  claim 5 . 
     
     
         7 . Use of a recombinant fusion protein for producing and formulating a pharmaceutical for a corresponding therapeutic method, wherein the recombinant fusion protein contains an amino acid sequence which comprises: (a) an Fc segment of an immunoglobulin, wherein the Fc segment consists of amino acids 18 to 243 of SEQ ID NO: 8, as component (A), and (b) an extracellular moiety of EDA2, as component (B), wherein component (B) comprises amino acids 266 to 410 of SEQ ID NO: 8. 
     
     
         8 . A method for reversing a genetically determined disease in a patient comprising administering the patient a pharmaceutical composition which comprises a recombinant fusion protein which contains an amino acid sequence which comprises: (a) an Fc segment of an immunoglobulin, wherein the Fc segment consists of amino acids 18 to 243 of SEQ ID NO: 8, as component (A), and (b) an extracellular moiety of EDA2, as component (B), wherein component (B) comprises amino acids 266 to 410 of SEQ ID NO: 8, and at least one pharmaceutically acceptable carrier material. 
     
     
         9 . The method of  claim 8 , wherein the genetically determined diseases comprises X-coupled hypohydrotic ectodermal dysplasia, genetically determined skin anomalies, anomalies of the hair, the teeth, the sweat glands and/or the sebaceous glands. 
     
     
         10 . The method of  claim 8 , wherein the recombinant fusion protein is administered to the patient in utero by administration to the mother of the patient in early pregnancy. 
     
     
         11 . The method of  claim 10 , wherein the recombinant fusion protein is administered to the patient's mother at least one during the first, second and/or third month of the pregnancy. 
     
     
         12 . A pharmaceutical composition comprising the recombinant fusion protein of  claim 2 , and a pharmaceutically acceptable carrier material.