Patent ID: 7118750

Claim:
A modified human TNFα molecule capable of raising neutralizing antibodies towards wild-type human TNFα following administration of said modified TNFα molecule to a human host, wherein at least one segment of the human TNFα molecule has been substituted by at least one peptide containing an immunodominant T cell epitope or a truncated form of said molecule containing an immunodominant T-cell epitope and one or both flanking regions of the human TNFα molecule comprising at least one TNFα B cell epitope, wherein the substitution is introduced in any one of the strands of the front β-sheet, in any one of the connecting loops or in any one of the B′, I, or D strands of the back β-sheet, or in any one of the connecting loops and in any one of the B′, I, or D strands of the back β-sheet, and which substitution leads to inactivation of the biological activity of human TNFα and which substitution essentially ensures preservation of the β-sheet structures of the B and G strands, wherein the inserted T cell epitope is promiscuous and immunogenic in a majority of human HLA class II types, wherein the epitope is from Tetanus toxoid, and wherein said modified human TNFα molecule is selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 8 SEQ ID NO: 10, SEQ ID NO: 14, SEQ ID NO: 16, and SEQ ID NO: 20.