Targeting tissue factor to activated platelets
The current invention relates to procoagulant fusion proteins, polynucleotides that encode said fusion proteins and cells that expresses said fusion proteins. Furthermore, the current invention relates to fusion proteins for use as a medicament. Individuals that have a coagulopathy, such as haemophilia A and B with or without inhibitors, may be treated with fusions proteins of the current invention.
1. A monoclonal antibody, or fragment thereof, that binds to an epitope on TREM-like transcript 1 (TLT-1) in a region selected from the group consisting of SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:8.
2. The monoclonal antibody, or fragment thereof, according to claim 1 , wherein the fragment is selected from the group consisting of a Fab fragment, a F(ab′) 2 fragment, a Fab′ fragment, a Fd fragment, a Fv fragment, a ScFv fragment, a dAb fragment, and an isolated complementarity determining region.
3. The monoclonal antibody, or fragment thereof, according to claim 1 , wherein the monoclonal antibody is a human monoclonal antibody.
4. The monoclonal antibody, or fragment thereof, according to claim 2 , wherein the Fab fragment is humanized.
5. The monoclonal antibody, or fragment thereof, according to claim 1 , wherein the TLT-1 region is SEQ ID NO:5.
6. The monoclonal antibody, or fragment thereof, according to claim 1 , wherein the TLT-1 region is SEQ ID NO:6.
7. The monoclonal antibody, or fragment thereof, according to claim 1 , wherein the TLT-1 region is SEQ ID NO:7.
8. The monoclonal antibody, or fragment thereof, according to claim 1 , wherein the TLT-1 region is SEQ ID NO:8.
9. The monoclonal antibody, or fragment thereof, according to claim 1 , wherein the epitope comprises residues V17, Q18, C19, H20, Y21, R22, L23, Q24, D25, V26, K27, A28, L63, G64, G65, G66, L67, L68, G89, A90, R91, G92, P93, Q94, I95, and L96 of SEQ ID NO: 5.
10. The monoclonal antibody, or fragment thereof, according to claim 1 , wherein the epitope comprises residues L36, P37, E38, G39, C40, Q41, P42, L43, V44, S45, S46, A47, V73, T74, L75, Q76, E77, E78, D79, A80, G81, E82, Y83, G84, C85, M86, R91, G92, P93, Q94, I95, L96, H97, R98, V99, S100, and L111 of SEQ ID NO: 5.
11. The monoclonal antibody, or fragment thereof, according to claim 1 , wherein the epitope comprises residues V17, Q18, C19, H20, Y21, R22, L23, Q24, D25, V26, K27, A28, R91, G92, P93, Q94, I95, L96, H97, R98, V99, S100, and L101 of SEQ ID NO: 5.
12. The monoclonal antibody, or fragment thereof, according to claim 1 , wherein the epitope comprises residues E5, T6, H7, K8, 19, G10, S11, L12, A13, E14, N15, A16, F17, S18, D19, P20, and A21 of SEQ ID NO: 7.