8CN9
Factor VII binding Fab of the bispecific antibody HMB-001 in complex with Factor VII
Summary for 8CN9
| Entry DOI | 10.2210/pdb8cn9/pdb |
| Descriptor | Fab light chain, Fab heavy chain, Coagulation factor VII, ... (8 entities in total) |
| Functional Keywords | factor vii, fab, bispecific antibody, hmb-001, blood clotting |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 20 |
| Total formula weight | 446753.59 |
| Authors | Schluckebier, G.,Johansson, E. (deposition date: 2023-02-22, release date: 2023-12-27, Last modification date: 2024-11-20) |
| Primary citation | Gandhi, P.S.,Zivkovic, M.,Ostergaard, H.,Bonde, A.C.,Elm, T.,Lovgreen, M.N.,Schluckebier, G.,Johansson, E.,Olsen, O.H.,Olsen, E.H.N.,de Bus, I.A.,Bloem, K.,Alskar, O.,Rea, C.J.,Bjorn, S.E.,Schutgens, R.E.,Sorensen, B.,Urbanus, R.T.,Faber, J.H. A bispecific antibody approach for the potential prophylactic treatment of inherited bleeding disorders. Nat Cardiovasc Res, 3:166-185, 2024 Cited by PubMed Abstract: Inherited bleeding disorders such as Glanzmann thrombasthenia (GT) lack prophylactic treatment options. As a result, serious bleeding episodes are treated acutely with blood product transfusions or frequent, repeated intravenous administration of recombinant activated coagulation factor VII (rFVIIa). Here we describe HMB-001, a bispecific antibody designed to bind and accumulate endogenous FVIIa and deliver it to sites of vascular injury by targeting it to the TREM (triggering receptor expressed on myeloid cells)-like transcript-1 (TLT-1) receptor that is selectively expressed on activated platelets. In healthy nonhuman primates, HMB-001 prolonged the half-life of endogenous FVIIa, resulting in its accumulation. Mouse bleeding studies confirmed antibody-mediated potentiation of FVIIa hemostatic activity by TLT-1 targeting. In ex vivo models of GT, HMB-001 localized FVIIa on activated platelets and potentiated fibrin-dependent platelet aggregation. Taken together, these results indicate that HMB-001 has the potential to offer subcutaneous prophylactic treatment to prevent bleeds in people with GT and other inherited bleeding disorders, with a low-frequency dosing regimen. PubMed: 39196196DOI: 10.1038/s44161-023-00418-4 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.4 Å) |
Structure validation
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