TNF muteins and uses thereof
AssigneeOxford University Innovation Limited
InventorsNicola R. Sibson, Daniel C. Anthony, Sandra J. Campbell
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Abstract
The present invention relates to tumour necrosis factor (TNF) muteins with improved properties, and in particular to TNF muteins which are agonists of, and bind selectively to, tumour necrosis factor receptor 1 (TNFR1). Compositions comprising the TNF muteins, which may additionally comprise appropriate anticancer agents or imaging agents are provided. The use of the muteins of the invention in methods of treating or detecting a tumour are also provided. The invention also provides nucleic acids (e.g. vectors) encoding the TNF muteins and host cells comprising the nucleic acids.
Claims19
A tumour necrosis factor (TNF) mutein comprising an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOS:
- 2 to 10 which comprises an amino acid sequence selected from any one of SEQ ID NOS:
- 12-20 at positions equivalent to positions 84 to 89 of SEQ ID NO:
- 1,
- wherein the mutein is an agonist of tumour necrosis factor receptor 1 (TNFR1) and binds selectively to TNFR1.
A tumour necrosis factor (TNF) mutein which comprises at least 4 amino acid mutations compared to a wild-type TNF sequence, wherein said mutations comprise:
- (a) a substitution of the residue at the position equivalent to position 84 of SEQ ID NO. 1;
- (b) a substitution of the residue at the position equivalent to position 85 of SEQ ID NO. 1;
- (c) a substitution of the residue at the position equivalent to position 88 of SEQ ID NO. 1;
- and
- (d) a substitution of the residue at the position equivalent to position 89 of SEQ ID NO. 1,
- wherein the mutein is an agonist of tumour necrosis factor receptor 1 (TNFR1) and binds selectively to TNFR1, and
- wherein the mutein comprises an amino acid sequence selected from any one of SEQ ID NOs:
- 2 to 10.
Dependencies are inferred from the claim text.