Anti-Human von Willebrand factor (vWF) (Caplacizumab) - 5 mg

All|Recombinant Antibodies>Biosimilar Recombinant Antibodies|Primary Monoclonal Antibodies

2 - 8°C Wet Ice

von Willebrand factor (vWF) is a plasma glycoprotein involved in clot formation via theadhesion of platelets to subendothelial collagen1, 2. A severe deficiency of the vWF-cleavingmetalloproteinase ADAMTS13 leads to acquired thrombotic thrombocytopenic purpura (aTTP), a rare autoimmune blood clotting disorder caused by anti-ADAMTS13 autoantibodies2. ReducedADAMTS13 activity leads to the accumulation of ultra-large vWF multimers in the blood. Thesebind to platelets, leading to the formation of platelet-rich microthrombi in the microvasculature.These microvascular occlusions ultimately lead to thrombocytopenia, hemolytic anemia, tissueischemia, and organ dysfunction. ADAMTS13 activity can be normalized via a combination ofplasma exchange, immunosuppression, and immunotherapy. ALX-0081 (Caplacizumab) was developed as a treatment for thrombosis in high-risk patientswith acute coronary syndrome, including treatment of aTTP2. Caplacizumab was generated as asingle-domain antibody fragment and consists of two identical, humanized building blockslinked by a 3-alanine linker2, 3. The precursor of Caplacizumab was isolated from a llamaimmunized with the recombinant A1 domain of vWF, humanized, and used to form amonovalent vWF-binding Nanobody (PMP12A2h1)3. The bivalent form was subsequentlyproduced in Escherichia coli using a secretory system. Caplacizumab inhibits the interaction between vWF and the platelet glycoprotein Ib-IX-Vreceptor, preventing platelet adhesion at high shear rates like those observed in stenosed arteries2, 3. Administration of caplacizumab in patients leads to rapid suppression of ristocetin cofactor, abiomarker for vWF activity, as well as reductions in VWF antigen and factor VIII.

≥ 5.0 mg/ml

vWF is found in blood plasma, the subendothelial matrix, storage granulesof endothelial cells, platelets, and megakaryocytes. vWF can also be found in macrophages, where it is bound and endocytosed during clearance.