Fc fusion proteins

Abstract

The invention relates to fusion proteins comprising at least a first domain and a second domain selected from a constant Fc immunoglobulin domain; wherein there is at least one amino acid overlap between the first domain and the second domain in the fusion region. In a preferred embodiment of the invention, the first domain is a ligand-binding receptor domain comprising the extra-cellular domain of a membrane-anchored receptor or a ligand-binding fragment thereof.

1 . A fusion protein comprising
 (i) a first domain comprising a ligand-binding domain of a TRAIL receptor or a TNF receptor fused to   (ii) a second domain comprising a portion of a   constant immunoglobulin domain, wherein there is at least one amino acid overlap between the first domain and the second domain in the fusion region.   
     
     
         2 . The fusion protein according to  claim 1 , wherein the receptor is TRAIL-R1 and the fusion protein comprises the amino acid sequence of SEQ ID NO: 21, 22, 23, or 24. 
     
     
         3 . The fusion protein according to  claim 1 , wherein the receptor is TRAIL-R2 and the fusion protein comprises the amino acid sequence of SEQ ID NO: 27, 28, 29, 30, 31, or 32. 
     
     
         4 . The fusion protein according to  claim 1 , wherein the receptor is TRAIL-R2 and the fusion protein comprises the amino acid sequence of SEQ ID NO: 34, 35, 36, 37, or 38. 
     
     
         5 . The fusion protein according to  claim 1 , wherein the receptor is TRAIL-R2 and the fusion protein comprises the amino acid sequence of SEQ ID NO: 41, 42, 43, or 44. 
     
     
         6 . The fusion protein according to  claim 1 , wherein the receptor is TRAIL-R3 and the fusion protein comprises the amino acid sequence of SEQ ID NO: 47, 48, 49, 50, 51, or 52. 
     
     
         7 . The fusion protein according to  claim 1 , wherein the receptor is TRAIL-R3 and the fusion protein comprises the amino acid sequence of SEQ ID NO: 54, 55, 56, 57, or 58. 
     
     
         8 . The fusion protein according to  claim 1 , wherein the receptor is TRAIL-R4 and the fusion protein comprises the amino acid sequence of SEQ ID NO: 61, 62, 63, or 64. 
     
     
         9 . The fusion protein according to  claim 1 , wherein the receptor is TNF-R1 and the fusion protein comprises the amino acid sequence of SEQ ID NO: 67, 68, 69, 70, 71, 72, or 73. 
     
     
         10 . The fusion protein according to  claim 1 , wherein the receptor is TNF-R2 and the fusion protein comprises the amino acid sequence of SEQ ID NO: 76, 77, 78, 79, 80, 81, or 82. 
     
     
         11 . The fusion protein of  claim 1 , wherein the second domain is an Fc fragment of a constant heavy immunoglobulin domain comprising the CH2 and CH3 domain. 
     
     
         12 . The fusion protein of  claim 1 , further comprising an N-terminal signal sequence. 
     
     
         13 . An isolated nucleic acid sequence encoding the fusion protein of  claim 1 . 
     
     
         14 . The nucleic acid sequence of  claim 13 , which is operatively linked to an expression control sequence. 
     
     
         15 . A vector comprising the nucleic acid sequence of  claim 13 . 
     
     
         16 . An isolated cell transformed or transfected with the nucleic acid sequence of  claim 13 . 
     
     
         17 . The cell of  claim 16 , which is a prokaryotic cell. 
     
     
         18 . The cell of  claim 16 , which is a eukaryotic cell. 
     
     
         19 . A pharmaceutical composition comprising the fusion protein of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         20 . A pharmaceutical composition comprising the nucleic acid sequence of  claim 13  and a pharmaceutically acceptable carrier.