The invention relates to ADAMTS13 protein variants comprising residues 1 to 685 of ADAMTS13 and wherein one or more N-linked glycosylation sites are added as compared to wild-type ADAMTS13 and/or one or more existing N-linked glycosylation sites are shifted as compared to wild-type ADAMTS13. The invention further relates to compositions comprising such ADAMTS13 variants, methods for their preparation and uses thereof, in particular as an antithrombotic agent, and in the treatment of thrombotic disease, thrombotic microangiopathy, thrombotic thrombocytopenic purpura (TTP), hemolytic—uremic syndrome (HUS), ischemic stroke, systemic thrombosis, COVID19, antiphospholipid syndrome, pre-eclampsia/HELLP syndrome, sepsis and sickle cell disease.

The present invention relates to ADAMTS-13 mutants and/or variant/s that display resistance to tPA cleavage and/or inactivation. The present disclosure further provides fibrinolytic compounds, compositions, combined compositions and kits comprising the ADAMTS-13 mutants disclosed herein, as well as uses thereof for treating coagulation related disorders.

This invention relates to methods of subcutaneous administration of ADAMTS13 formulations to a treat a disease or condition associated with ADAMTS13 and VWF dysfunction. Furthermore, evidence of the unexpectedly high bioavailability of ADAMTS13 formulations administered subcutaneously is provided herein.

Among other aspects, the present invention relates to cell culture conditions for producing high molecular weight vWF, in particular, highly multimericWF with a high specific activity and ADAMTS13 with a high specific activity. The cell culture conditions of the present invention can include, for example, a cell culture medium with an increased copper concentration and/or cell culture supernatant with a low ammonium (NH.sub.4.sup.+) concentration. The present invention also provides methods for cultivating cells in the cell culture conditions to express high molecular weight vWF and rA13 having high specific activities.

This invention relates to methods of subcutaneous administration of ADAMTS13 formulations to a treat a disease or condition associated with ADAMTS13 and VWF dysfunction. Furthermore, evidence of the unexpectedly high bioavailability of ADAMTS13 formulations administered subcutaneously is provided herein.

This disclosure provides methods and compositions for treating TTP based on transfusion of a relatively small number of genetically modified red blood cells. The genetically modified red blood cells express a fusion protein including a fragment of ADAMTS13 that is enzymatically active against von Willebrand factor (VWF). The fragments of ADAMTS13 can be resistant to the inhibitors, e.g., the auto-immune antibodies, which are responsible for the acquired form of TTP.

The disclosure provides a method for treating sickle cell disease with A Disintegrin And Metalloproteinase with Thrombospondin type 1 motif, member-13 (ADAMTS13). The disclosure provides a method for increasing ADAMTS13-mediated von Willebrand factor (VWF) cleavage in a subject suffering from sickle cell disease by administering ADAMTS13. The disclosure also provides a method of treating a vaso-occlusive crisis (VOC) in a subject suffering from sickle cell disease by administering ADAMTS13 after the onset of the VOC. The disclosure also provides a method of preventing a VOC in a subject suffering from sickle cell disease by administering ADAMTS13 prior to the onset of the VOC. The disclosure also provides a method of determining the efficacy of a treatment for a VOC in a mouse model.

This invention relates to methods of subcutaneous administration of ADAMTS13 formulations to a treat a disease or condition associated with ADAMTS13 and VWF dysfunction. Furthermore, evidence of the unexpectedly high bioavailability of ADAMTS13 formulations administered subcutaneously is provided herein.

Among other aspects, the present invention relates to cell culture conditions for producing high molecular weight vWF, in particular, highly multimericWF with a high specific activity and ADAMTS13 with a high specific activity. The cell culture conditions of the present invention can include, for example, a cell culture medium with an increased copper concentration and/or cell culture supernatant with a low ammonium (NH.sub.4.sup.+) concentration. The present invention also provides methods for cultivating cells in the cell culture conditions to express high molecular weight vWF and rA13 having high specific activities.

Provided herein are methods for recanalization of occluded blood vessels in a subject having an infarction. The method includes a step of administering to the subject a therapeutically effective amount of isolated ADAMTS13 protein at particular dosages and ranges of times after detection of the infarction. As described herein, ADAMTS13 advantageously recanalizes occluded blood vessels and reduces infarction size, even when administered a prolonged period after stable occlusion. Accordingly, such methods and compositions are useful for the treatment of infractions caused by blood vessel occlusion.